輝瑞 (PFE) 2018 Q4 法說會逐字稿

Good day, everyone, and welcome to Pfizer's Fourth Quarter 2018 Earnings Conference Call.

大家好，歡迎來到輝瑞 2018 年第四季度收益電話會議。

Today's call is being recorded.

今天的通話正在錄音中。

At this time, I would like to turn the call over to Mr. Chuck Triano, Senior Vice President of Investor Relations.

在這個時候，我想把電話轉給投資者關係高級副總裁 Chuck Triano 先生。

Please go ahead, sir.

請繼續，先生。

Good morning, and thank you for joining us today to review Pfizer's fourth quarter and full year 2018 performance and 2019 financial guidance and business outlook.

早上好，感謝您今天加入我們，回顧輝瑞公司 2018 年第四季度和全年業績以及 2019 年財務指導和業務展望。

I'm joined today by our CEO, Albert Bourla; Frank D'Amelio, our CFO; Mikael Dolsten, President of Worldwide Research and Development; Angela Hwang, Group President, Pfizer Biopharmaceuticals Group; John Young, our Chief Business Officer; and Doug Lankler, General Counsel.

今天，我們的首席執行官 Albert Bourla 加入了我的行列；我們的首席財務官 Frank D'Amelio； Mikael Dolsten，全球研發總裁；輝瑞生物製藥集團總裁 Angela Hwang；我們的首席商務官 John Young；和總法律顧問 Doug Lankler。

Slides that will be presented on this call can be viewed on our website, pfizer.com/investors.

可以在我們的網站 pfizer.com/investors 上查看將在本次電話會議上展示的幻燈片。

You'll see here that Slide 3 covers our legal disclosures.

您會在此處看到幻燈片 3 涵蓋了我們的法律披露。

Albert and Frank will now make prepared remarks, and then we will move to a question-and-answer session.

Albert 和 Frank 現在將發表準備好的發言，然後我們將進入問答環節。

With that, I'll now turn the call over to Albert Bourla.

有了這個，我現在將電話轉給 Albert Bourla。

Albert?

艾伯特？

Thank you, Chuck, and good morning, everyone.

謝謝查克，大家早上好。

During my remarks, I will speak about our performance for the year, the continued advancement of our pipeline and the strategy we have put in place to return Pfizer to a period of sustained growth, following the impact of the Lyrica LOE that will negatively impact our growth in both 2019 and 2020.

在我的發言中，我將談到我們今年的業績、我們管道的持續推進以及我們為使輝瑞恢復持續增長而製定的戰略，因為 Lyrica LOE 的影響將對我們產生負面影響2019 年和 2020 年均有增長。

Frank will then provide the details regarding the fourth quarter and our 2019 financial guidance.

Frank 然後將提供有關第四季度和我們 2019 年財務指導的詳細信息。

Pfizer had another solid year in 2018.

輝瑞在 2018 年又是一個穩健的一年。

Revenues for the year were up 2% operationally.

全年營業收入增長 2%。

We saw continued growth in several of our biggest-selling medicines and vaccines in emerging markets and in biosimilars.

我們看到我們在新興市場和生物仿製藥領域最暢銷的幾種藥物和疫苗的持續增長。

These increases were partially offset by the $1.7 billion in LOE impacts as well as decreases in the Legacy Established Products portfolio in developed markets and in our sterile injectables portfolio, primarily due to continued legacy Hospira product shortages in the U.S.

這些增長部分被 17 億美元的 LOE 影響以及發達市場的傳統產品組合和我們的無菌注射劑組合的減少所抵消，這主要是由於美國的傳統 Hospira 產品持續短缺。

I will begin with a few words regarding the performance of each of our businesses, starting with Pfizer Innovative Health.

我將首先介紹一下我們每項業務的績效，首先是輝瑞創新健康。

This business had another strong year, growing its top line 6% operationally, thanks to the continued strength of several key brands, including Ibrance, Eliquis and Xeljanz globally and Prevenar 13, primarily in emerging markets.

由於幾個主要品牌的持續實力，包括全球的 Ibrance、Eliquis 和 Xeljanz 以及主要在新興市場的 Prevenar 13，該業務又迎來了強勁的一年，其運營收入增長了 6%。

I would also remind you that Viagra transferred from PIH to PEH at the beginning of 2018.

我還要提醒你，偉哥在 2018 年初從 PIH 轉移到 PEH。

So if you exclude Viagra from the calculation, the growth would have been 9% operationally.

因此，如果將偉哥排除在計算之外，運營增長率將達到 9%。

For full year 2018, Ibrance revenues were $4.1 billion, which represented an increase of 32% operationally.

2018 年全年，Ibrance 的收入為 41 億美元，運營增長了 32%。

While approximately 50% of eligible U.S. patients are getting a CDK inhibitor, in combination with endocrine therapy, many are still receiving endocrine monotherapy or chemotherapy.

雖然大約 50% 符合條件的美國患者正在服用 CDK 抑製劑，並結合內分泌治療，但許多人仍在接受內分泌單一療法或化療。

We continue to educate the oncology community about the benefits of Ibrance therapy.

我們繼續向腫瘤學界宣傳 Ibrance 療法的好處。

We remain confident in Ibrance leadership in the class based on the strength of our data, significant first-mover advantage, and most importantly, the continued positive patient experience with more than 200,000 patients prescribed the medicine worldwide since its launch.

基於我們的數據實力、顯著的先發優勢，以及最重要的是，自推出以來，全球超過 200,000 名患者開具了持續積極的患者體驗，我們仍然對 Ibrance 在同類產品中的領導地位充滿信心。

Our current growth driver for Ibrance remains outside of the U.S., particularly in developed Europe and Japan, and we had another quarter of solid growth here.

我們目前 Ibrance 的增長動力仍然在美國以外，特別是在發達的歐洲和日本，我們在這裡又實現了四分之一的穩健增長。

Ibrance has achieved reimbursement in the majority of international developed markets and despite increasing competition has maintained greater than 90% of total CDK class volume in these key markets.

Ibrance 已在大多數國際發達市場實現報銷，儘管競爭日益激烈，但在這些主要市場中仍保持了 CDK 類總量的 90% 以上。

For Xtandi, alliance revenues in the U.S. were up 18% for the full year and when combined with our royalty income on ex-U.

對於 Xtandi，美國的聯盟收入全年增長了 18%，加上我們在前美國的特許權使用費收入。

S. sales totaled nearly $1 billion in 2018.

2018 年美國銷售額總計近 10 億美元。

We are continuing to see an increased number of urologists prescribing Xtandi, and our launch of the expanded indication in non-metastatic prostate cancer in the U.S., following the July approval, made the first and only FDA-approved oral medication for both non-metastatic and metastatic castration-resistant prostate cancer.

我們繼續看到越來越多的泌尿科醫師開出 Xtandi 的處方，並且我們在美國推出了針對非轉移性前列腺癌的擴展適應症，繼 7 月獲得批准後，它成為第一個也是唯一一個獲得 FDA 批准的口服藥物，用於治療非轉移性前列腺癌和非轉移性前列腺癌。和轉移性去勢抵抗性前列腺癌。

We continued to see growth in Xtandi throughout this year, and we remain focused on demonstrating the value of moving Xtandi into earlier treatment settings.

今年全年，我們繼續看到 Xtandi 的增長，我們仍然專注於展示將 Xtandi 轉移到早期治療環境中的價值。

In December, along with our alliance partner, Astellas, we announced that the Phase 3 ARCHES trial evaluating Xtandi plus ADT in men with metastatic hormone-sensitive prostate cancer met its primary endpoint, significantly improving radiographic progression-free survival versus ADT alone.

12 月，我們與我們的聯盟合作夥伴 Astellas 一起宣布，評估 Xtandi 加 ADT 治療轉移性激素敏感性前列腺癌男性的 3 期 ARCHES 試驗達到了主要終點，與單獨使用 ADT 相比，顯著改善了影像學無進展生存期。

These data further differentiate Xtandi from the competition, both branded and generic.

這些數據進一步將 Xtandi 與品牌和非專利競爭產品區分開來。

We are engaging global health authorities in discussions regarding the potential of an expanded indication for Xtandi, and we remain confident that Xtandi will be one of the pillars of our Oncology portfolio for years to come.

我們正在與全球衛生當局就擴大 Xtandi 適應症的潛力進行討論，我們仍然相信 Xtandi 將成為我們未來幾年腫瘤產品組合的支柱之一。

But this year, Xeljanz had a tremendous performance with revenues increasing 33% operationally to $1.8 billion.

但今年，Xeljanz 的表現非常出色，營業收入增長了 33%，達到 18 億美元。

Our fourth quarter results continued a pattern of extremely strong performance for Xeljanz with scripts up 35% compared with the prior year quarter.

我們第四季度的業績延續了 Xeljanz 極其強勁的表現模式，與去年同期相比，腳本增長了 35%。

This was driven by continued growth in rheumatoid arthritis prescriptions as well as increased contributions from the drug's recent expansion into psoriatic arthritis and ulcerative colitis.

這是由類風濕性關節炎處方的持續增長以及該藥物最近擴展到銀屑病關節炎和潰瘍性結腸炎的貢獻增加所推動的。

We look forward to these new indications becoming even more meaningful contributors in 2019, particularly in ulcerative colitis.

我們期待這些新適應症在 2019 年成為更有意義的貢獻者，尤其是在潰瘍性結腸炎方面。

Eliquis had another strong year with alliance revenue and direct sales growing 35% operationally to $3.4 billion.

Eliquis 又迎來了強勁的一年，聯盟收入和直接銷售額增長了 35%，達到 34 億美元。

Lastly, our Consumer Healthcare business grew 3% operationally for the year with revenues totaling $3.6 billion.

最後，我們的消費者保健業務全年運營增長 3%，收入總計 36 億美元。

In December, we entered into a definitive agreement with GSK, under which we have agreed to create a new Consumer Healthcare joint venture.

12 月，我們與葛蘭素史克 (GSK) 達成了最終協議，根據該協議，我們同意創建一家新的消費者保健合資企業。

We expect the transaction to close in the second half of 2019, subject, of course, to customary closing conditions, including GSK shareholder approval and required regulatory approvals.

我們預計交易將在 2019 年下半年完成，當然，這取決於慣例成交條件，包括 GSK 股東批准和所需的監管批准。

Turning now to Pfizer Essential Health.

現在轉向 Pfizer Essential Health。

While revenues for the year declined, we, once again, saw strong operational growth, both in emerging markets and in our biosimilars portfolio.

儘管今年的收入有所下降，但我們在新興市場和我們的生物仿製藥產品組合中再次實現了強勁的運營增長。

Emerging markets revenue for the business grew 11% operationally for the year to $7.8 billion.

該業務在新興市場的營業收入全年增長 11%，達到 78 億美元。

Some of the biggest growth drivers in emerging markets were Lipitor, up 19% operationally; Norvasc, up also 19% operationally; and Sterile Injectables, up 13% operationally.

新興市場中一些最大的增長驅動力是立普妥，在運營上增長了 19%； Norvasc，在運營方面也增長了 19%；和無菌注射劑，在運營上增長了 13%。

Our biosimilars business grew 41% operationally in 2018 to approximately $769 million.

我們的生物仿製藥業務在 2018 年增長了 41%，達到約 7.69 億美元。

We received FDA approvals for 2 biosimilars in 2018, and we see the potential for up to 4 additional approvals in 2019.

我們在 2018 年獲得了 FDA 對 2 種生物仿製藥的批准，我們認為 2019 年有可能再獲得多達 4 種批准。

PEH growth in emerging markets and biosimilars was more than offset by lower revenues for our Legacy Established Products portfolio in developed markets and product supply shortages in the Sterile Injectable business.

新興市場和生物仿製藥的 PEH 增長被我們在發達市場的傳統成熟產品組合的收入下降和無菌注射劑業務的產品供應短缺所抵消。

In the U.S. Sterile Injectable business, manufacturing supply constraints continued to impact our top line.

在美國無菌注射劑業務中，製造供應限制繼續影響我們的收入。

We expect these issues to be significantly improved by the end of 2019 and continue to expect this business to be a solid growth contributor in the future.

我們預計到 2019 年底這些問題將得到顯著改善，並繼續期望該業務在未來成為穩健的增長貢獻者。

As you are aware, as of the start of our 2019 fiscal year, Pfizer is now organized into 3 businesses: Pfizer Biopharmaceuticals Group, a science-based innovative medicines business led by Angela Hwang; Upjohn, an off-patent branded and generic medicines business headquartered in China and led by Michael Goettler that is bringing 20 of our most iconic brands to more than 100 markets around the world; and our Consumer Health Care business led by Chris Slager, which is preparing to become part of a joint venture I mentioned earlier.

如您所知，截至我們的 2019 財年開始，輝瑞現在分為 3 個業務部門：輝瑞生物製藥集團，這是一個由 Angela Hwang 領導的以科學為基礎的創新藥物業務； Upjohn，一家總部位於中國並由 Michael Goettler 領導的專利過期品牌和仿製藥企業，將我們最具標誌性的 20 個品牌帶到全球 100 多個市場；以及我們由 Chris Slager 領導的消費者保健業務，該業務正準備成為我之前提到的合資企業的一部分。

Now let me turn my attention to our R&D pipeline.

現在讓我把注意力轉向我們的研發管道。

This year, we saw a wave of new approvals from our pipeline, including 4 targeted cancer agents over the last 4 months of 2018.

今年，我們看到了一波新的批准浪潮，包括 2018 年最後 4 個月的 4 種靶向癌症藥物。

In total, we received 7 key approvals in 2018, spanning both new molecular entities and line extensions which will allow us to serve a broader patient population.

總的來說，我們在 2018 年獲得了 7 項關鍵批准，涵蓋新的分子實體和產品線擴展，這將使我們能夠為更廣泛的患者群體提供服務。

In terms of the recent news, let me touch on some of the key milestones we have achieved since our third quarter call.

就最近的新聞而言，讓我談談自第三季度電話會議以來我們取得的一些關鍵里程碑。

In rare disease, FDA accepted our NDA filing for tafamidis for the treatment of ATTR cardiomyopathy with a PDUFA date in July.

在罕見疾病中，FDA 接受了我們關於 tafamidis 的 NDA 申請，用於治療 PDUFA 日期為 7 月的 ATTR 心肌病。

As a reminder, we estimate less than 1% of ATTR cardiomyopathy patients have been diagnosed.

提醒一下，我們估計只有不到 1% 的 ATTR 心肌病患者被確診。

And currently, there are no approved treatments for this disease, making it an incredibly underserved market.

目前，還沒有針對這種疾病的批准治療方法，使其成為一個服務不足的市場。

In Oncology, we have several promising developments.

在腫瘤學方面，我們有幾個有前途的發展。

We received FDA approvals for LORBRENA, a third-generation ALK inhibitor for lung cancer; and for DAURISMO for acute myeloid leukemia.

第三代 ALK 肺癌抑製劑 LORBRENA 獲得 FDA 批准； DAURISMO 用於治療急性髓性白血病。

In the oncology biosimilar space, we received a positive CHMP opinion for ZIRABEV, a potential biosimilar to Avastin.

在腫瘤生物仿製藥領域，我們收到了 CHMP 對 ZIRABEV 的正面意見，ZIRABEV 是一種潛在的阿瓦斯汀生物仿製藥。

We have initiated clinical studies for a second cancer vaccine applicable in major solid tumor types, and we advanced a second CDK inhibitor for Ibrance-resistant cancer into clinical studies.

我們已經啟動了適用於主要實體瘤類型的第二種癌症疫苗的臨床研究，並將針對 Ibrance 耐藥癌症的第二種 CDK 抑製劑推進到臨床研究中。

In Vaccines, we've started a Phase 3 trial for our next-generation 20-valent pneumococcal conjugate vaccine for adults 18 and older.

在疫苗方面，我們已經開始了針對 18 歲及以上成年人的下一代 20 價肺炎球菌結合疫苗的 3 期試驗。

In Inflammation & Immunology, our JAK3 inhibitor for moderate to severe alopecia areata started a pivotal Phase 2b/3 trial.

在炎症與免疫學領域，我們用於中度至重度斑禿的 JAK3 抑製劑開始了關鍵的 2b/3 期試驗。

In Internal Medicine, Pfizer and our partner, Eli Lilly, announced this morning positive top line results from a Phase 3 study evaluating tanezumab 2.5 milligram or 5 milligram in patients with moderate to severe osteoarthritis pain.

在內科領域，輝瑞和我們的合作夥伴禮來公司今天上午宣布了一項在中度至重度骨關節炎疼痛患者中評估 tanezumab 2.5 毫克或 5 毫克的第 3 期研究的積極頂線結果。

Looking ahead, we see the potential in 2019 for several inflection points that will further advance our pipeline.

展望未來，我們認為 2019 年有可能出現幾個拐點，這將進一步推進我們的產品線。

These include potential U.S. approvals for the combination of BAVENCIO and Inlyta for first-line renal cell carcinoma as well as for up to 4 biosimilars: trastuzumab, bevacizumab, rituximab and adalimumab, which, when taken together, represent a potential blockbuster opportunity for Pfizer.

其中包括美國可能批准 BAVENCIO 和 Inlyta 聯合治療一線腎細胞癌，以及多達 4 種生物仿製藥：曲妥珠單抗、貝伐珠單抗、利妥昔單抗和阿達木單抗，這些藥物加在一起，代表了輝瑞的潛在重磅炸彈機會。

We also expect Phase 3 readouts for rivipansel in sickle cell disease and for our JAK1 in atopic dermatitis as well as further Phase 3 data readouts for tanezumab, which has the potential to address the serious unmet needs of the more than 27 million Americans living with osteoarthritis and the more than 33 million suffering chronic low back pain.

我們還期待 rivipansel 在鐮狀細胞病和我們的 JAK1 在特應性皮炎中的第 3 階段讀數以及 tanezumab 的進一步第 3 階段數據讀數，這有可能解決超過 2700 萬患有骨關節炎的美國人嚴重未滿足的需求以及超過 3300 萬患有慢性腰痛的人。

Thanks to these achievements and expected milestones, we believe we are extremely well positioned for what we expect to become an era of sustained top line growth with leverage to the bottom line growth rate, following the impact of the Lyrica LOE.

得益於這些成就和預期的里程碑，我們相信，在 Lyrica LOE 的影響之後，我們已經做好了充分準備，迎接我們期望成為一個持續收入增長的時代，並利用對利潤增長率的槓桿作用。

We view this as a significant opportunity because 3 very positive trends are intersecting at the same time: first, macro trends such as an aging population and a rising middle class in emerging markets increasing the number of people seeking access to both innovative and established medicines; second, the continued advancement of what we believe is the best pipeline in our history with good breadth and strong innovation.

我們認為這是一個重要的機會，因為 3 個非常積極的趨勢同時交織在一起：首先，新興市場人口老齡化和中產階級崛起等宏觀趨勢增加了尋求獲得創新藥物和成熟藥物的人數；其次，繼續推進我們認為是我們歷史上最好的管道，具有廣泛的廣度和強大的創新能力。

And finally, after Lyrica, we expect to enjoy the benefits of a dramatic abatement in LOEs until the second half of the next decade.

最後，在 Lyrica 之後，我們希望在下一個十年的下半年之前享受 LOE 大幅減少的好處。

Our job now is to stay the course, take the steps necessary to pivot to growth.

我們現在的工作是堅持到底，採取必要的步驟轉向增長。

Our strategy for doing so can be summed up in 3 words: innovating for growth.

我們這樣做的策略可以用三個詞來概括：創新促進增長。

This means we must advance both scientific innovation that significantly improves current standards of care and commercial innovation that addresses patient access and affordability issues.

這意味著我們必須推進顯著提高當前護理標準的科學創新和解決患者獲取和負擔能力問題的商業創新。

To deliver these innovations, we have taken steps to ensure we have the right organizational structure in place and that our resources are focused in the right areas.

為了實現這些創新，我們已採取措施確保我們擁有正確的組織結構，並將我們的資源集中在正確的領域。

To improve operational effectiveness and create capacity for value-creating work, we have reorganized our operations to simplify them.

為了提高運營效率並為創造價值的工作創造能力，我們重組了我們的運營以簡化它們。

We are initiating an enterprise-wide digital effort to speed up drug development, enhance patient and physician experiences and access and leverage technology and robotics to simplify and automate our processes.

我們正在發起一項全企業範圍的數字化努力，以加快藥物開發，增強患者和醫生的體驗，並獲取和利用技術和機器人技術來簡化和自動化我們的流程。

And we are significantly reallocating capital across the enterprise by investing more aggressively in profitable growth drivers and reducing resources in areas of lower strategic importance.

我們正在通過更積極地投資於盈利增長驅動因素並減少戰略重要性較低領域的資源，在整個企業範圍內重新分配資本。

This includes significant planned reductions in indirect SI&A spending, much of which will be reallocated to R&D.

這包括計劃大幅削減間接 SI&A 支出，其中大部分將重新分配給研發。

And within R&D, the entire increase in spending will be project related with overhead costs actually anticipated to come down.

在研發方面，支出的全部增長將與實際預計會下降的管理費用相關。

In addition, of course, to all of this, we have the financial flexibility to continue to undertake additional shareholder-friendly capital allocation initiatives.

當然，除此之外，我們還擁有財務靈活性，可以繼續採取其他有利於股東的資本配置計劃。

We see a growing dividend as an important part of our investment thesis.

我們將不斷增長的股息視為我們投資主題的重要組成部分。

We also have the ability to deploy capital, as appropriate, in other areas, whether that be share repurchases or business development initiatives.

我們也有能力在其他領域酌情部署資本，無論是股票回購還是業務發展計劃。

Where at the current time, we are focused on smaller tuck-in type acquisitions and licensing opportunities for mid-stage compounds.

目前，我們專注於中期化合物的小型收購和許可機會。

Of course, our business isn't without its challenges.

當然，我們的業務並非沒有挑戰。

Most significantly, we need to ensure that our innovation and risk-taking is rewarded in the marketplace while doing all we can to ensure affordable access for patients.

最重要的是，我們需要確保我們的創新和冒險在市場上得到回報，同時盡我們所能確保患者能夠負擔得起。

To this end, we continue to work with governments, policymakers, payers and other players in the healthcare ecosystem to advocate for pro-innovation policies that benefit patients, our company and our industry as a whole.

為此，我們繼續與醫療保健生態系統中的政府、政策制定者、付款人和其他參與者合作，倡導有利於患者、我們公司和整個行業的創新政策。

All the steps we are taking are designed to enable us to achieve our purpose of delivering breakthroughs that change patients' lives.

我們正在採取的所有步驟旨在使我們能夠實現我們的目標，即提供改變患者生活的突破。

In summary, we see our improved growth profile coming more clearly into focus, and we believe we remain well positioned to deliver new medicines for patients, prepare the company for accelerated growth in the future and create enhanced shareholder value.

總而言之，我們看到我們改善的增長狀況越來越成為人們關注的焦點，我們相信我們仍然有能力為患者提供新藥，為公司未來的加速增長做好準備，並創造更高的股東價值。

I will now turn it over to Frank to provide details on the quarter and our outlook for 2019.

我現在將其轉交給弗蘭克，以提供有關該季度的詳細信息和我們對 2019 年的展望。

Frank?

坦率？

Thanks, Albert.

謝謝，艾伯特。

Good day, everyone.

今天是個好日子。

As always, the charts I'm reviewing today are included in our webcast.

與往常一樣，我今天要查看的圖表包含在我們的網絡廣播中。

Now moving on to the financials.

現在轉向財務。

Fourth quarter 2018 revenues were approximately $14 billion, which reflects operational growth of $657 million or 5% and the unfavorable impact of foreign exchange, $383 million or 3%.

2018 年第四季度的收入約為 140 億美元，反映了 6.57 億美元或 5% 的運營增長以及 3.83 億美元或 3% 的外匯不利影響。

Our Innovative Health business recorded 10% operational revenue growth in fourth quarter 2018 driven primarily by Ibrance in international markets, Eliquis and Xeljanz globally and Prevenar 13 in the emerging markets, all of which were partially offset by the loss of exclusivity of Viagra in the U.S. in December of 2017 and the resulting shift in reporting of Viagra revenues in the U.S. and Canada to the Essential Health business at the beginning of 2018 and decreased revenues for Enbrel in most developed Europe markets, mainly due to continued biosimilar competition.

我們的創新健康業務在 2018 年第四季度錄得 10% 的營業收入增長，主要受國際市場的 Ibrance、全球的 Eliquis 和 Xeljanz 以及新興市場的 Prevenar 13 的推動，所有這些都被偉哥在美國失去獨家經營權所部分抵消。 2017 年 12 月，偉哥在美國和加拿大的收入報告在 2018 年初轉移到基本健康業務，並且 Enbrel 在大多數發達歐洲市場的收入減少，這主要是由於生物仿製藥的持續競爭。

Revenues for our Essential Health business in the fourth quarter decreased 3% operationally, primarily due to a 13% operational decline in the Legacy Established Products portfolio in developed markets, driven mainly by industry-wide pricing challenges in the U.S. and generic competition; a 14% operational decline in the Sterile Injectables portfolio in developed markets, primarily due to increased competition across the portfolio and continued legacy Hospira product shortages in the U.S.; and a 10% operational decline in the Peri-LOE Products portfolio in developed markets, mainly as a result of expected declines in Lyrica in developed Europe and Pristiq, all of which were partially offset by the addition of Viagra revenues from the U.S. and Canada that were previously recorded in the IH business; a 10% operational growth in emerging markets, primarily reflecting growth across the LEP and SIP portfolios in China; and operational growth of 31% from biosimilars in developed markets, primarily from Inflectra in certain channels in the U.S.

第四季度我們的基本健康業務收入在運營上下降了 3%，這主要是由於發達市場的 Legacy Established Products 業務下降了 13%，這主要是受美國全行業定價挑戰和仿製藥競爭的推動；發達市場無菌注射劑產品組合的運營下降 14%，這主要是由於整個產品組合的競爭加劇以及美國傳統 Hospira 產品持續短缺；發達市場的 Peri-LOE 產品組合運營下降 10%，這主要是由於歐洲發達市場的 Lyrica 和 Pristiq 的預期下降，所有這些都被來自美國和加拿大的偉哥收入的增加部分抵消以前記錄在 IH 業務中；新興市場 10% 的運營增長，主要反映了中國 LEP 和 SIP 投資組合的增長；發達市場生物仿製藥業務增長 31%，主要來自美國某些渠道的 Inflectra

In the fourth quarter, we recorded a $0.07 loss per share compared with earnings per share of $2.02 in the year ago quarter, which was primarily due to the unfavorable impact of the non-recurrence of a $10.7 billion benefit recorded in fourth quarter 2017 to reflect the December 2017 enactment of the Tax Cut and Jobs Act; higher asset impairment charges, primarily associated with generic sterile injectable products acquired in connection with Pfizer's 2015 acquisition of Hospira and higher restructuring/implementation costs, partially offset by the non-recurrence of net losses on the early retirement of debt recorded in the fourth quarter of 2017 as well as higher revenues in fourth quarter of '18 compared to last year.

第四季度，我們錄得每股虧損 0.07 美元，而去年同期的每股收益為 2.02 美元，這主要是由於 2017 年第四季度錄得的 107 億美元收益的非經常性不利影響，以反映2017 年 12 月頒布的《減稅和就業法》；更高的資產減值費用，主要與輝瑞 2015 年收購 Hospira 相關的仿製藥無菌注射劑產品以及更高的重組/實施成本有關，部分被 2018 年第四季度記錄的提前清償債務的非經常性淨虧損所抵消2017 年以及 18 年第四季度與去年相比的更高收入。

Adjusted diluted EPS for the fourth quarter was $0.64 versus $0.62 in the year ago quarter.

第四季度調整後的攤薄每股收益為 0.64 美元，而去年同期為 0.62 美元。

The increase was primarily due to higher revenues and lower SI&A expenses.

增長的主要原因是收入增加和 SI&A 費用減少。

I want to point out that diluted weighted average shares outstanding declined by 152 million shares versus the year ago quarter due primarily to our ongoing share repurchase program, reflecting the impact of shares repurchased during 2018, partially offset by dilution related to share-based employee compensation programs.

我想指出的是，與去年同期相比，稀釋加權平均流通股減少了 1.52 億股，這主要是由於我們正在進行的股票回購計劃，反映了 2018 年股票回購的影響，部分被與基於股票的員工薪酬相關的稀釋所抵消程式。

As I previously mentioned, foreign exchange negatively impacted fourth quarter 2018 revenues by approximately $383 million and positively impacted adjusted cost of sales, adjusted SI&A expenses and adjusted R&D expenses in the aggregate by $408 million.

正如我之前提到的，外匯對 2018 年第四季度的收入產生了約 3.83 億美元的負面影響，並對調整後的銷售成本、調整後的 SI&A 費用和調整後的研發費用產生了 4.08 億美元的積極影響。

As a result, foreign exchange had a negligible impact on adjusted diluted EPS compared to the year ago quarter.

因此，與去年同期相比，外匯對調整後攤薄每股收益的影響微乎其微。

As you can see on this chart, we've met or exceeded all components of our 2018 financial guidance.

正如您在此圖表中看到的，我們已經達到或超過了 2018 年財務指南的所有組成部分。

Turning now to our 2019 guidance.

現在轉向我們的 2019 年指南。

I'd first like to note that our guidance reflects a full year contribution of revenue and expenses from Consumer Healthcare.

我首先要指出的是，我們的指導反映了消費者保健的全年收入和支出貢獻。

Our revenue guidance of $52 billion to $54 billion reflects an anticipated $2.6 billion headwind from products that have recently lost or are expected to lose marketing exclusivity shortly, including the LOE for Lyrica in the U.S. in June 2019 as well as an anticipated $900 million negative impact from unfavorable changes in foreign exchange rates relative to the U.S. dollar compared to actual FX rates from 2018, partially offset by continued strong growth expected from key product franchises, including Ibrance, Eliquis, Xeljanz and Xtandi as well as contributions from newly launched products and indications.

我們 520 億美元至 540 億美元的收入指引反映了最近失去或預計將很快失去營銷獨占權的產品帶來的 26 億美元逆風，包括 2019 年 6 月美國 Lyrica 的 LOE 以及預期的 9 億美元負面影響與 2018 年以來的實際匯率相比，外匯匯率相對於美元的不利變化，部分被主要產品特許經營（包括 Ibrance、Eliquis、Xeljanz 和 Xtandi）預期的持續強勁增長以及新推出的產品和適應症的貢獻所抵消.

Moving on to other elements of our 2019 financial guidance.

繼續我們 2019 年財務指南的其他內容。

Compared with 2018 actual results, the midpoints of these ranges imply higher adjusted cost of sales as a percentage of revenues, resulting primarily from the anticipated LOE of Lyrica in the U.S.; lower adjusted SI&A expenses, reflecting a 3% to 4% increase indirect spend for product marketing promotion being offset by a reduction in indirect spend; and higher adjusted R&D expenses to support our late-stage and emerging early-stage pipelines.

與 2018 年的實際結果相比，這些範圍的中點意味著調整後的銷售成本佔收入的百分比更高，這主要是由於 Lyrica 在美國的預期 LOE；降低調整後的 SI&A 費用，反映出產品營銷推廣的間接支出增加 3% 至 4%，但被間接支出的減少所抵消；以及更高的調整後研發費用，以支持我們的後期和新興的早期管道。

In addition, we anticipate significantly lower adjusted other income this year compared to 2018.

此外，我們預計今年調整後的其他收入與 2018 年相比將大幅下降。

As I highlighted on our third quarter earnings call, we expected the core components of other income, net interest income and expense, income from royalties and the ViiV joint venture as well as our pension credit to net to approximately flat or 0. We have since refined our forecast and are now estimating approximately $100 million of income for 2019.

正如我在第三季度財報電話會議上強調的那樣，我們預計其他收入的核心組成部分、淨利息收入和支出、來自特許權使用費和 ViiV 合資企業的收入以及我們的養老金信貸淨值將大致持平或為 0。我們已經改進了我們的預測，現在估計 2019 年的收入約為 1 億美元。

This is approximately $1.2 billion less in 2018 adjusted other income, which included $586 million of net gains on equity investments as well as $464 million of income from collaborations, out-licensing arrangements and the sale of compound rights.

這比 2018 年調整後的其他收入減少約 12 億美元，其中包括 5.86 億美元的股權投資淨收益以及 4.64 億美元的合作收入、對外許可安排和出售複合權利。

In 2019 and forward, we will exclude gains or losses on equity investments from adjusted results because of their inherent volatility and because we do not believe they reflect the results of our core business.

在 2019 年及以後，我們將從調整後的結果中排除股權投資的收益或損失，因為它們具有固有的波動性，而且我們認為它們不能反映我們核心業務的結果。

As we report our quarterly results in 2019, the 2018 adjusted results will be presented, excluding these gains, while income from collaborations, out-licensing arrangements and the sale of compound rights will remain in adjusted results.

在我們報告 2019 年季度業績時，將公佈 2018 年調整後的業績，不包括這些收益，而來自合作、對外許可安排和復合權利出售的收入將保留在調整後的業績中。

Our guidance does not assume any potential future milestone income until it is actually recorded.

在實際記錄之前，我們的指南不會假設任何潛在的未來里程碑收入。

We expect our effective tax rate on adjusted income to be approximately 16%, which we believe is sustainable for the foreseeable future.

我們預計調整後收入的有效稅率約為 16%，我們認為這在可預見的未來是可持續的。

We expect 2019 adjusted diluted EPS to be in the range of $2.82 to $2.92.

我們預計 2019 年調整後的攤薄每股收益將在 2.82 美元至 2.92 美元之間。

As I just mentioned, this range now excludes gains and losses on equity investments, which favorably impacted 2018 adjusted diluted EPS by $0.08.

正如我剛才提到的，這個範圍現在不包括股權投資的收益和損失，這對 2018 年調整後的攤薄每股收益產生了 0.08 美元的有利影響。

This range also reflects an anticipated $0.06 negative impact from changes in foreign exchange rates and expected share repurchases of approximately $9 billion in 2019.

這一範圍還反映了 2019 年外匯匯率變化預計產生的 0.06 美元負面影響以及預計約 90 億美元的股票回購。

Now I want to highlight how our 2019 guidance compares to 2018 revenue and adjusted diluted EPS.

現在我想強調我們 2019 年的指導與 2018 年的收入和調整後的攤薄每股收益相比如何。

The midpoint of our 2019 revenue guidance, excluding the anticipated $900 million negative impact from foreign exchange, implies flat to slightly improved operational performance compared to 2018 despite facing an anticipated $2.6 billion of LOE headwinds this year, which is $900 million more than 2018.

我們 2019 年收入指引的中點，不包括預期的 9 億美元的外匯負面影響，意味著與 2018 年相比，運營業績持平或略有改善，儘管今年預計面臨 26 億美元的 LOE 逆風，比 2018 年多 9 億美元。

On adjusted diluted EPS, the midpoint of our 2019 guidance, excluding the anticipated $0.06 negative impact from foreign exchange, also implies comparable operational performance compared to 2018 after removing the $0.08 gain on equity investments.

就調整後的攤薄每股收益而言，我們 2019 年指引的中點（不包括預期的 0.06 美元的外匯負面影響）也意味著在剔除 0.08 美元的股權投資收益後，運營業績與 2018 年相當。

I want to highlight that despite the significant challenges of the Lyrica LOE this year, we expect our 2019 operational performance for revenues and adjusted diluted EPS, excluding foreign exchange, to be comparable with 2018.

我想強調的是，儘管今年 Lyrica LOE 面臨重大挑戰，但我們預計 2019 年的運營業績和調整後的攤薄每股收益（不包括外匯）將與 2018 年相當。

Moving on to key takeaways.

繼續討論要點。

We delivered strong Q4 2018 financial results with 5% operational revenue growth and 3% adjusted diluted EPS growth compared with the year ago quarter.

我們在 2018 年第四季度實現了強勁的財務業績，與去年同期相比，營業收入增長了 5%，調整後的攤薄每股收益增長了 3%。

Our 2019 financial guidance ranges imply comparable operational performance for revenues and adjusted diluted EPS when excluding the impact of foreign exchange in 2018 net gains on equity investments despite the anticipated loss of market exclusivity in the U.S. for Lyrica on June 30, 2019.

我們的 2019 年財務指導範圍意味著在排除 2018 年外匯淨收益對股權投資的影響時，收入和調整後攤薄每股收益具有可比性，儘管 Lyrica 預計將於 2019 年 6 月 30 日在美國失去市場獨占權。

We accomplished multiple product and pipeline milestones since our previous quarterly update, and we returned $20.2 billion to shareholders in 2018 through a combination of dividends and share repurchases.

自上一季度更新以來，我們實現了多個產品和管道里程碑，我們在 2018 年通過股息和股票回購相結合的方式向股東返還了 202 億美元。

Finally, we remain committed to delivering attractive shareholder returns in 2019 and beyond.

最後，我們仍然致力於在 2019 年及以後提供有吸引力的股東回報。

Now I'll turn it back to Chuck.

現在我會把它轉回給查克。

Thank you, Frank, and thank you, everybody.

謝謝你，弗蘭克，謝謝大家。

Operator, can we please poll for questions now?

接線員，我們現在可以輪詢問題嗎？

(Operator Instructions) Your first question comes from Steve Scala from Cowen.

（操作員說明）您的第一個問題來自 Cowen 的 Steve Scala。

Congratulations on a strong 2018 and a solid 2019 outlook.

祝賀 2018 年表現強勁，2019 年展望穩健。

A couple of questions.

幾個問題。

First, to clarify, has BAVENCIO plus Inlyta been filed in first-line renal cell?

首先澄清一下，BAVENCIO plus Inlyta是否已經備案在一線腎細胞？

And if yes, was this based on the PFS data or was OS met since ESMO?

如果是，這是基於 PFS 數據還是自 ESMO 以來就滿足了 OS？

And if only PFS, then how will the regulators view this given that KEYTRUDA plus Inlyta achieved both PFS and OS?

如果只有 PFS，那麼鑑於 KEYTRUDA 加 Inlyta 實現了 PFS 和 OS，監管機構將如何看待這一點？

So that's the first question.

這是第一個問題。

Second question is can you craft an expectation for us for the tafamidis rollout?

第二個問題是您能否為我們制定對 tafamidis 推出的期望？

Will this be more like a traditional cardiovascular rollout which can be sluggish or more like a novel orphan drug filling an unmet need which can be much more rapid?

這會更像是緩慢的傳統心血管產品推出，還是更像是一種可以更快地滿足未滿足需求的新型孤兒藥？

Thank you, Steve.

謝謝你，史蒂夫。

I think maybe John can answer the BAVENCIO-Inlyta question?

我想也許 John 可以回答 BAVENCIO-Inlyta 的問題？

Yes.

是的。

Thanks for the question, Steve.

謝謝你的問題，史蒂夫。

So we obviously would confirm filing when it's formally -- a filing has formally been received by the FDA.

因此，我們顯然會在正式提交時確認提交 - FDA 已正式收到申請。

So what I can at this point in time is that we're in the filing phase for that study and that indication.

所以我現在能做的是我們正處於該研究和該指示的備案階段。

Yes.

是的。

Thank you, John.

謝謝你，約翰。

And Angela, maybe you can speak a little bit about the tafamidis rollout plans.

安吉拉，也許你可以談談 tafamidis 推出計劃。

Sure.

當然。

So we're really excited about the potential launch of tafamidis for ATTR cardiomyopathy.

因此，我們對可能推出用於治療 ATTR 心肌病的 tafamidis 感到非常興奮。

We do see this as a rare disease, but it is a severely underdiagnosed rare disease, particularly because there is no treatment today and diagnosis involves the use of invasive heart biopsies.

我們確實認為這是一種罕見疾病，但它是一種嚴重未被診斷的罕見疾病，特別是因為目前沒有治療方法，而且診斷涉及使用侵入性心臟活檢。

We know that from autopsy data that there are about probably 100,000 potential patients in the U.S, the prevalence of this disease, but we also know that only about 1% of these patients are diagnosed today in the U.S. So really, from a launch perspective, diagnosis is going to be a key focus of our launch plans.

我們從屍檢數據中知道，美國大約有 100,000 名潛在患者，這種疾病的患病率，但我們也知道，這些患者中只有約 1% 今天在美國被診斷出來。因此，從發布的角度來看，診斷將成為我們啟動計劃的重點。

And in this regard, diagnosis and market development is a key area for Pfizer.

而在這方面，診斷和市場開發是輝瑞的重點領域。

It's a key area of expertise for Pfizer.

這是輝瑞的一個關鍵專業領域。

Let's just take example the diagnosis of the ALK mutation for Xalkori in non-small cell lung cancer.

讓我們以 Xalkori 在非小細胞肺癌中的 ALK 突變診斷為例。

At the launch of Xalkori, the diagnosis rate here was about 1%, but we know that today, it has reached diagnosis rates of 80% to 90%.

在 Xalkori 推出時，這裡的診斷率大約是 1%，但我們知道，今天，它已經達到了 80% 到 90% 的診斷率。

So we have a strong record of success in developing new markets across not just the ALK example but many therapeutic areas, but the one thing we've also learned from this is that it does take time.

因此，我們不僅在 ALK 示例中，而且在許多治療領域，在開發新市場方面都有成功的良好記錄，但我們也從中學到的一件事是，這確實需要時間。

So our launch is going to be focused on a number of factors: first, in creating suspicion for this disease by both cardiologists as well as patients through education around the symptoms of cardiomyopathy.

因此，我們的發布將集中在許多因素上：首先，通過圍繞心肌病症狀的教育，讓心髒病專家和患者對這種疾病產生懷疑。

In parallel, we also want to increase the utilization of noninvasive scintigraphy versus heart biopsy as a means of diagnosis.

同時，我們還希望提高無創閃爍顯像與心臟活檢作為診斷手段的利用率。

We know that there are about 15,000 scintigraphy machines in the U.S. today, and these machines are already being used routinely to diagnose other cardiac diseases.

我們知道今天美國大約有 15,000 台閃爍掃描儀，這些機器已經被常規用於診斷其他心髒病。

So we know that this is a routine procedure, and it is already reimbursed.

所以我們知道這是一個常規程序，已經報銷了。

So when we look in totality, what we see for tafamidis is the following: we have excellent data.

因此，當我們從整體上看時，我們對 tafamidis 的看法如下：我們擁有出色的數據。

We have compelling patient benefits.

我們有令人信服的患者福利。

We have deep expertise and commercial footprint in cardiology.

我們在心髒病學方面擁有深厚的專業知識和商業足跡。

We also have a track record of success in creating new markets, and we plan to bring all of this to bear in diagnosing and treating the cardiomyopathy patient.

我們在開拓新市場方面也有成功的記錄，我們計劃將所有這些用於診斷和治療心肌病患者。

Thank you, Angela.

謝謝你，安吉拉。

And needless to say that for both BAVENCIO and Inlyta and tafamidis, we are really very excited about the future based on the strength of the data of both studies.

不用說，對於 BAVENCIO 和 Inlyta 以及 tafamidis，基於兩項研究數據的實力，我們對未來真的非常興奮。

Your next question comes from Umer Raffat from Evercore.

你的下一個問題來自 Evercore 的 Umer Rafat。

First, just wanted to -- since this has been such a topical thing, your commentary on large M&A, maybe for the broader audience, can you reiterate your thoughts?

首先，只是想——因為這是一個熱門話題，你對大型併購的評論，也許是為了更廣泛的聽眾，你能重申一下你的想法嗎？

Would be very curious what your preference are in large versus mid and how you define smaller acquisitions in terms of dollars.

會很好奇您對大型收購和中型收購的偏好是什麼，以及您如何用美元來定義小型收購。

Second, just quickly on R&D.

其次，快速進行研發。

On tafamidis, my question, I guess, is there wasn't a free acid -- couldn't you have developed a free acid form for 20 milligram also?

關於 tafamidis，我想我的問題是，是否沒有游離酸——你們不能也開發出 20 毫克的游離酸形式嗎？

And I ask because presumably that could have helped with the European pricing structures given your existing 20-milligram approval there.

我之所以問，是因為考慮到您現有的 20 毫克批准，這可能有助於歐洲的定價結構。

And finally, Frank, just your thoughts on absolute SG&A and R&D dollar changes in the next 5-year time frame, just mostly trying to understand your thought process on operating margin evolution plus therapy.

最後，弗蘭克，只是你對未來 5 年時間框架內 SG&A 和 R&D 美元絕對變化的看法，主要是想了解你對營業利潤率演變和治療的思考過程。

Thank you very much, Umer.

非常感謝你，烏默爾。

I will recap my thoughts on M&A, and then Mikael can deal with the R&D question about tafamidis.

我會回顧一下我對併購的看法，然後 Mikael 可以處理關於 tafamidis 的研發問題。

Look, as we have said consistently and we started saying that from the second quarter last year and the third quarter last year and now we are repeating in the fourth quarter earnings call, business development is not a strategy.

看，正如我們一貫所說的那樣，我們從去年第二季度和去年第三季度開始說，現在我們在第四季度的財報電話會議上重複，業務發展不是戰略。

It is a way to execute your strategy, and our strategy has been very clear.

這是一種執行戰略的方式，我們的戰略已經很明確了。

Our strategy is top line growth through the introduction of breakthrough medicines.

我們的戰略是通過引入突破性藥物實現收入增長。

And we sounded, as I said in my comments, into innovating for growth.

正如我在評論中所說，我們聽起來正在為增長而創新。

And we believe that right now, we are very well positioned to have seen this strategy because of the combination of one virtual LOE-free period after the Lyrica LOE until '25, the mid of the decade; and also the introduction of a great pipeline, what we think is the greatest pipeline ever.

我們相信，現在，我們非常有能力看到這一戰略，因為在 Lyrica LOE 之後的一個虛擬 LOE 自由期的組合，直到 25 年，即十年中期；還有一個偉大的管道的引入，我們認為這是有史以來最偉大的管道。

So with that in mind, when we have that hand to play, what we need to do is to make sure that we maximize the chances of achieving the potential that those new launches are expecting to bring.

因此，考慮到這一點，當我們有手可玩時，我們需要做的是確保我們最大限度地發揮這些新產品預期帶來的潛力。

And this means that execution is extremely important.

這意味著執行力極其重要。

Right now, execution can make the difference.

現在，執行可以發揮作用。

And the large M&A, it's not that we'll not have right now, matching our growth profile, but it could take -- derail us from execution because a large M&A requires thousands of people to work together thus to integrate the 2 companies.

而大型併購，並不是說我們現在沒有，與我們的增長狀況相匹配，但它可能會讓我們偏離執行軌道，因為大型併購需要數千人共同努力，從而整合兩家公司。

That being said, first of all, we never say never, so we are examining all opportunities.

話雖這麼說，首先，我們從不說永遠，所以我們正在研究所有機會。

And also, we do plan to deploy capital to enhance our growth profile.

而且，我們確實計劃部署資本以增強我們的增長前景。

It's just that this time, the capital that we plan to deploy has a very different -- slightly different direction and focus than before.

只是這一次，我們計劃部署的資本有一個非常不同的——與以前略有不同的方向和重點。

Before, we were trying to do revenues now or soon.

以前，我們正試圖現在或很快就獲得收入。

This was, more or less, the focus of our M&A dogma and is exactly what we needed at the time.

這或多或少是我們併購信條的重點，也正是我們當時所需要的。

We were dealing with lack of revenue growth, and we needed to bring either thesis that could enhance the strategy to break the company at the time or it could bring revenue streams that will enhance the growth profile that was actually very bad at the time.

我們正在處理收入增長不足的問題，我們需要提出可以加強當時打破公司戰略的論點，或者它可以帶來收入流，以增強當時實際上非常糟糕的增長狀況。

Right now, the dogma is changing, and it is how can we bring assets to enhance even further a pipeline to make our growth sustained.

現在，教條正在改變，我們如何才能利用資產來進一步加強管道，使我們的增長得以持續。

And because we have a very strong R&D machine that right now I fully trust their ability to choose assets and also develop them.

而且因為我們擁有非常強大的研發機器，現在我完全相信他們選擇資產和開發資產的能力。

This is why our strategy is to deploy capital towards this direction.

這就是為什麼我們的策略是將資金投向這個方向。

As I said, though, we never say never.

不過，正如我所說，我們從不說永不。

And of course, we will never lose our flexibility to deploy capital if we see the opportunities in the best way to achieve our premise.

當然，如果我們以實現我們前提的最佳方式看到機會，我們將永遠不會失去部署資本的靈活性。

And with that, I will ask Mikael to comment.

然後，我將請 Mikael 發表評論。

So thank you for the question.

謝謝你的提問。

We have under breakthrough designation moved tafamidis registration and the 20-milligram formulation for once-a-day administration was to unused in clinical studies, and it has priority review.

我們已經在突破性指定下轉移了 tafamidis 註冊，每天一次給藥的 20 毫克製劑未在臨床研究中使用，它具有優先審評權。

And Albert pointed out potential FDA action date in July.

艾伯特指出 FDA 可能在 7 月採取行動。

We have also filed a 61-milligram formulation that we think is a very convenient alternative that is under standard review as expected and would potentially be approved in the fall.

我們還提交了一個 61 毫克的配方，我們認為它是一種非常方便的替代品，正如預期的那樣正在接受標準審查，並有可能在秋季獲得批准。

This would offer patients the very best choices for a therapy that has this really strong data set and a consistency in cardiomyopathy.

這將為患者提供最好的治療選擇，該治療具有非常強大的數據集和心肌病的一致性。

And also, I would ask Frank to comment on the question about SI&A and R&D expenses.

另外，我想請 Frank 對有關 SI&A 和研發費用的問題發表評論。

Yes.

是的。

So if you think about SI&A, just -- we've printed, what, $14.2 billion in 2018.

因此，如果您考慮 SI&A，我們在 2018 年印刷了 142 億美元。

We guided to $13.5 billion to $14.5 billion, so the midpoint is $14 billion, a couple hundred million lower than what we showed in 2018 on actuals.

我們的指導價為 135 億美元至 145 億美元，因此中點為 140 億美元，比我們 2018 年的實際數字低幾億美元。

And we actually swung a few hundred million from indirect SI&A to direct SI&A.

實際上，我們將幾億美元從間接 SI&A 轉為直接 SI&A。

So in SI&A is we're working our way through the Lyrica patent cliff, so think about that will take place in 2019, 2020.

所以在 SI&A 中，我們正在努力克服 Lyrica 專利懸崖，所以想想這將在 2019 年、2020 年發生。

We'll remain tough on SI&A.

我們將對 SI&A 保持強硬態度。

On R&D, as you look at R&D, we guided $7.8 billion to $8.3 billion.

在研發方面，就研發而言，我們指導了 78 億美元至 83 億美元。

We spent about $8 billion last year.

去年我們花費了大約 80 億美元。

We'll watch the R&D number.

我們將關注研發數字。

But given how our late-stage pipeline we expect to grow, we think R&D will continue to grow.

但考慮到我們預期的後期管道將如何增長，我們認為研發將繼續增長。

Once we get past the Lyrica LOE, beginning 2021 with 2020 as a base, we expect that top line to grow in the mid-single digits, and we will make sure we leverage that relative to the bottom line, get operating leverage, margin expansion so that the revenues are growing at a rate that's more than what the expenses are.

一旦我們超過 Lyrica LOE，從 2020 年開始，以 2020 年為基數，我們預計收入將以中等個位數增長，我們將確保我們將其與利潤相關聯，獲得運營槓桿，利潤率擴張這樣收入的增長速度就超過了支出的速度。

Thank you very much.

非常感謝。

And I see, Mikael, do you want to make a comment?

我明白了，Mikael，你想發表評論嗎？

I just wanted to make sure since you had this keen culmination interest rumor that the 61-milligram free asset formulation is equivalent to the 80-milligram top dose that we used in the clinical trial.

我只是想確定，因為你有這個強烈的高潮興趣謠言，61 毫克的自由資產配方相當於我們在臨床試驗中使用的 80 毫克的最高劑量。

So that would be a single tablet as an alternative and potential available latest for pending review.

因此，這將是一個單一的平板電腦作為替代品，並且可能是最新的待審。

So there is no difference in dose.

所以劑量沒有區別。

It is just the dosage form.

它只是劑型。

Perfect.

完美的。

Your next question comes from Chris Schott from JPMorgan.

你的下一個問題來自摩根大通的 Chris Schott。

So just 2 here.

所以這裡只有 2 個。

The first was on tanezumab.

第一個是 tanezumab。

Can you just talk about the profile that you see emerging from these first 2 studies, I guess, specifically on RPOA type 2 and this case of osteonecrosis.

你能談談你從前兩項研究中看到的概況嗎，我想，特別是關於 RPOA 2 型和這個骨壞死病例。

I just want to understand, you've had some dialogue as you're starting the studies on acceptable levels of these signals, can you just confirm that what you're seeing so far is below what you think's an acceptable threshold in terms of safety?

我只是想了解，當您開始研究這些信號的可接受水平時，您已經進行了一些對話，您能否確認您目前所看到的在安全方面低於您認為可接受的閾值？

And then my second question was about Xtandi and key drivers going forward.

然後我的第二個問題是關於 Xtandi 和未來的主要驅動因素。

And here, I guess, do you see the traction you'd hope to see with the label expansion and do you expect any impact as we think about generic ZYTIGA, Eliquis on 2019?

在這裡，我想，你是否看到了你希望通過標籤擴展看到的牽引力，你是否期望在我們考慮 2019 年通用 ZYTIGA 和 Eliquis 時產生任何影響？

Thank you, Chris.

謝謝你，克里斯。

Let's have John start the tanezumab -- answer the tanezumab question and then maybe Mikael can jump in.

讓 John 啟動 tanezumab——回答 tanezumab 問題，然後 Mikael 就可以加入了。

And then Angela, can you please take the Xtandi question?

然後 Angela，你能回答 Xtandi 的問題嗎？

Okay.

好的。

Thanks for the question, Chris.

謝謝你的問題，克里斯。

So let me just sort of context it just by saying from our review of the 2 studies that have read out today, we continue to believe that tanezumab has the potential to offer a new nanoguide treatment for sustained efficacy for moderate to severe OA, osteoarthritis, and chronic lower back pain patients who are not receiving adequate relief or can tolerate other analgesics and also for cancer pain patients, and those are the patient populations in our pivotal studies.

因此，讓我簡單介紹一下背景，從我們對今天讀出的 2 項研究的回顧來看，我們仍然相信 tanezumab 有潛力提供一種新的納米導向治療，以持續有效治療中度至重度 OA、骨關節炎、和慢性下背痛患者，他們沒有得到足夠的緩解或不能耐受其他鎮痛藥，也適用於癌症疼痛患者，這些是我們關鍵研究中的患者群體。

We also see that tanezumab has the potential to address serious high unmet need for those patients.

我們還看到，tanezumab 有可能解決這些患者嚴重未滿足的嚴重需求。

We estimate that there are around 27 million Americans living with osteoarthritis, 33 million patients living with chronic lower back pain.

我們估計大約有 2700 萬美國人患有骨關節炎，3300 萬患者患有慢性腰痛。

And many of those patients failed to achieve adequate pain relief despite treatment with various types of pain medications.

儘管使用了各種類型的止痛藥進行治療，但其中許多患者未能充分緩解疼痛。

Additionally, we also know that the misuse of an addiction to opioids leads to more than 115 deaths everyday in the United States.

此外，我們還知道，濫用阿片類藥物成癮在美國每天導致超過 115 人死亡。

And so it's estimated that 21% to 19% of patients prescribed with opioids for chronic pain misuse them and 8% to 12% development an opioid use disorder.

因此，據估計，有 21% 到 19% 的服用阿片類藥物治療慢性疼痛的患者會濫用藥物，而 8% 到 12% 的患者會發展為阿片類藥物使用障礙。

So we remain encouraged by the emerging clinical profile for tanezumab although we recognize that many questions still need to be answered.

因此，我們仍然對 tanezumab 的新興臨床資料感到鼓舞，儘管我們認識到仍有許多問題需要回答。

Last year, we saw data from 1 Phase 3 OA study, which was study 1056.

去年，我們看到了 1 項 3 期 OA 研究的數據，即研究 1056。

That population represented about 10% of the total number of patients in our Phase 3 program, which overall includes 6 Phase 3 studies and around 7,000 patients in osteoarthritis, chronic lower back pain and cancer pain.

該人群約占我們第 3 期計劃患者總數的 10%，該計劃總共包括 6 項第 3 期研究和約 7,000 名骨關節炎、慢性腰痛和癌症疼痛患者。

So today's study, we announced earlier on today, we shared top line results from our second Phase 3 OA study, which is 1057.

所以今天的研究，我們今天早些時候宣布，我們分享了我們第二階段 3 OA 研究的頂線結果，即 1057。

And that population represents another 12% of the total number of patients in our Phase 3 program.

該人群占我們第 3 階段計劃患者總數的另外 12%。

So in summary, I would say we continue to see data sets read out.

所以總而言之，我想說我們繼續看到數據集被讀出。

We have more than 3/4 of the total number of patients in our Phase 3 program still to read out although the profile is still emerging, and that's to say there are many questions that we still need to answer about the profile of the product.

在我們的第 3 階段計劃中，我們仍有超過 3/4 的患者總數有待宣讀，儘管概況仍在出現，這就是說，關於產品的概況，我們仍有許多問題需要回答。

But overall, we remain very positive.

但總的來說，我們仍然非常樂觀。

Mikael, maybe you can add specific answer to Chris' question.

Mikael，也許你可以為 Chris 的問題添加具體的答案。

Thank you, John.

謝謝你，約翰。

That was a terrific overview of why we are excited about this new emerging potential pain drug class for patient in great need for new opportunities to treat difficult disease.

這是一個很好的概述，說明了為什麼我們對這種新出現的潛在止痛藥類別感到興奮，因為患者非常需要新的機會來治療疑難病症。

With the 1057 study, it was -- as we have projected and believe to expect RPOA in low single-digit percent.

通過 1057 研究，它是——正如我們所預測並相信預期 RPOA 處於低個位數百分比。

In 1057, it was just above 2%, versus 1056, above 1%.

1057 年略高於 2%，而 1056 年高於 1%。

This is the range that we have assumed will come out in these trials.

這是我們假設將在這些試驗中出現的範圍。

And across now 1,000 patients, we have RPOA at 1.7%.

在現在的 1,000 名患者中，我們的 RPOA 為 1.7%。

Within the RPOA, I just wanted to punctuate that the majority of them are of Type 1, the milder case, with only joint narrowing -- joint space narrowing and infrequent symptomatology, and only 1/3 of them about -- are tied with more significant radiological changes.

在 RPOA 中，我只是想指出，他們中的大多數屬於 1 型，較輕的病例，只有關節狹窄——關節間隙狹窄和不常見的症狀，其中只有 1/3——與更多相關顯著的放射學變化。

Finally, we had one case of osteonecrosis, which is in line with our expectations that it's going to be a rare event.

最後，我們有一個骨壞死病例，這符合我們的預期，即這將是一個罕見的事件。

We have now more than 1,000 patients in osteoarthritis treated with tanezumab, which gives us quite good opportunity to see an emerging drug profile with robust efficacy and as expected, adverse event profile, that for these patient type seems to me provide really favorable benefit risk, given the alternative treatments are few and would offer a way for us to treat difficult pain, avoiding abuse dependencies such as with opioid.

我們現在有超過 1,000 名骨關節炎患者接受了 tanezumab 治療，這讓我們有很好的機會看到具有強大療效的新興藥物概況，並且正如預期的那樣，不良事件概況，在我看來，對於這些患者類型提供了非常有利的獲益風險，考慮到替代療法很少，並且可以為我們提供一種治療困難疼痛的方法，避免濫用阿片類藥物等依賴性。

And let me just conclude and say please remember that the type of patients in 1057 and 56 have been through at least 3 different classes of analgesics and on average, had OA for more than 6 years and have reported OA with significant impact on their ability to function in everyday life.

讓我總結一下，請記住，1057 和 56 中的患者類型至少使用了 3 種不同類型的鎮痛藥，平均而言，OA 超過 6 年，並且報告 OA 對他們的能力有重大影響在日常生活中發揮作用。

So for them, it certainly is an important opportunity to treat their disease.

所以對於他們來說，這當然是治療他們疾病的一個重要契機。

And let me conclude with reminding you that total joint replacement was similar across placebo and tanezumab treated, again, an important finding for us.

最後，讓我提醒您，安慰劑和 tanezumab 治療的全關節置換術相似，這對我們來說也是一個重要發現。

Thank you very much, Mikael.

非常感謝你，米凱爾。

And Angela, key drivers of growth for Xtandi, please?

還有 Angela，請問是 Xtandi 增長的主要驅動力嗎？

Sure.

當然。

So let me begin by talking a little bit about how well Xtandi did in 2018 and how pleased we are with its performance but also very optimistic about its future.

因此，讓我首先談談 Xtandi 在 2018 年的表現以及我們對它的表現有多滿意，但也對它的未來非常樂觀。

As you heard Albert say, it is -- Xtandi is one of the pillars of our Oncology business.

正如你聽到阿爾伯特所說的那樣——Xtandi 是我們腫瘤業務的支柱之一。

So full year 2018, we grew 18%.

2018 年全年，我們增長了 18%。

Q4 versus Q4 '17, we grew 12%.

與 17 年第四季度相比，我們增長了 12%。

And then if you include royalty revenues, Xtandi actually achieved over $1 billion in 2018.

然後，如果包括版稅收入，Xtandi 在 2018 年實際上實現了超過 10 億美元。

But when we step back and take a look at its growth strategy, I would describe it as follows:

但當我們退一步看它的增長戰略時，我會這樣描述它：

First, it's our base business in metastatic castrate-resistant prostate cancer.

首先，這是我們在轉移性去勢抵抗性前列腺癌方面的基礎業務。

This was our first indication, and our growth strategy here has been focused on driving uptake around urologists, and we're really pleased with the progress that we've seen here.

這是我們的第一個跡象，我們在這裡的增長戰略一直專注於推動泌尿科醫生的吸收，我們對我們在這裡看到的進展感到非常滿意。

Today, more than 30% of our new scripts are written by urologists, and we're continuing to see market share growth in this segment.

今天，我們超過 30% 的新腳本是由泌尿科醫生編寫的，而且我們繼續看到這一領域的市場份額增長。

The second segment and growth segment is the non-metastatic castrate-resistant prostate cancer segment, and this is the PROSPER data.

第二段和生長段是非轉移性去勢抵抗性前列腺癌段，這是PROSPER數據。

And we've seen very positive trends here as well since the launch of PROSPER in July of 2018.

自 2018 年 7 月推出 PROSPER 以來，我們在這裡也看到了非常積極的趨勢。

Just in 6 months, our market share is quadruple that of ERLEADA or if you look at it a different way, it's equivalent to the combination of chemo use and ERLEADA combined.

僅僅在 6 個月內，我們的市場份額是 ERLEADA 的四倍，或者如果你換個角度看，它相當於化療使用和 ERLEADA 的結合。

You may not see it in total sales yet, but that's because the new patients are coming into therapy, new patients are coming every day.

你可能還沒有在總銷售額中看到它，但那是因為新患者正在接受治療，每天都有新患者來。

So you may not see the full impact of this pool of patients, which is still accumulating, so it will take time to realize.

所以你可能看不到這個仍在積累的患者群體的全部影響，所以需要時間來實現。

Finally and our last opportunity and the one that we're really excited about is in the hormone-sensitive prostate cancer patient population because this is where the duration of therapy would be the longest.

最後也是我們最後的機會，也是我們真正感到興奮的機會是在激素敏感的前列腺癌患者群體中，因為這是治療持續時間最長的地方。

And here, there are 2 patient segments.

在這裡，有 2 個患者部分。

The first is based off of our ARCHES data, is the metastatic hormone-sensitive patient and there are about 38,000 new patients coming in a year.

第一個是基於我們的 ARCHES 數據，是轉移性激素敏感患者，每年大約有 38,000 名新患者。

As you know, the results of ARCHES was announced in December and it will be presented at ASCO in February.

如您所知，ARCHES 的結果於 12 月公佈，並將於 2 月在 ASCO 上公佈。

We look forward to our discussions with the FDA to potentially support an expanded indication for Xtandi here.

我們期待著與 FDA 的討論，以潛在地支持擴大 Xtandi 的適應症。

The second segment of growth is going to be in the non-metastatic hormone-sensitive patients.

增長的第二部分將出現在非轉移性激素敏感患者中。

And here, there are about 30,000 new patients a year.

而在這裡，每年大約有 30,000 名新患者。

This is being studied in the EMBARK trial, which will read out next year.

EMBARK 試驗正在對此進行研究，該試驗將於明年宣讀。

So in totality, we believe that we have excellent data, and we also have the potential for new indications, and this will enable Pfizer to make significant impact on patients' lives but importantly, to change the standard of care for prostate cancer.

所以總的來說，我們相信我們擁有出色的數據，我們也有可能獲得新的適應症，這將使輝瑞能夠對患者的生活產生重大影響，但重要的是，改變前列腺癌的護理標準。

You also asked a question on the impact of generic ZYTIGA.

您還問了一個關於 ZYTIGA 仿製藥影響的問題。

And here, we expect the ZYTIGA generics to have a minimal impact on our business.

在這裡，我們希望 ZYTIGA 仿製藥對我們的業務影響最小。

Typically, generic impact is greatest with the originator brand.

通常，仿製藥對原創品牌的影響最大。

In this instance, Xtandi also has indications that are different from ZYTIGA.

在這種情況下，Xtandi 也有不同於 ZYTIGA 的適應症。

And in addition to that, our dosing frequency is different.

除此之外，我們的給藥頻率也不同。

We also are -- we also don't have the requirement for steroid co-administration, and we also have differences in our monitoring requirements.

我們也是——我們也沒有類固醇聯合給藥的要求，我們在監測要求方面也有差異。

So I think that all of these will stand well in terms of making switching less likely and for the impact on Xtandi to be minimal as we expect.

因此，我認為所有這些在降低轉換的可能性以及對 Xtandi 的影響如我們預期的那樣最小方面都將站得住腳。

Thank you, Angela.

謝謝你，安吉拉。

And as I said before, for the BAVENCIO-Inlyta and tafamidis products equally excited about tanezumab and the Xtandi, particularly with the new indications that are coming.

正如我之前所說，對於 BAVENCIO-Inlyta 和 tafamidis 產品，tanezumab 和 Xtandi 同樣令人興奮，尤其是在即將出現新適應症的情況下。

Your next question comes from Alex Arfaei from BMO Capital Markets.

您的下一個問題來自 BMO Capital Markets 的 Alex Arfaei。

Great.

偉大的。

First on Xeljanz, you obviously have strong momentum there.

首先在 Xeljanz 上，你顯然在那裡有很強的動力。

You have a formidable competitor coming expected this year.

預計今年你會有一個強大的競爭對手。

They have a lot of rebates leverage.

他們有很多回扣槓桿。

You have more JAKs coming, TNF biosimilars, TYK2, obviously a lot of activity in this market so I'm just wondering how you're thinking about the commercial dynamics in major immunology markets.

你有更多的 JAKs，TNF 生物仿製藥，TYK2，顯然在這個市場上有很多活動，所以我只是想知道你如何看待主要免疫學市場的商業動態。

And then a follow-up in emerging markets.

然後是新興市場的跟進。

Obviously, very strong performance for your legacy products like in cardiovascular disease, Lipitor and so on.

顯然，您的遺留產品（如心血管疾病、立普妥等）的表現非常強勁。

Just wondering how sustainable is that in your view.

只是想知道在您看來這有多可持續。

Yes.

是的。

On Xeljanz, I will ask Angela to comment, but just to make an initial comment about -- Xeljanz already has, this year, has $1.8 billion.

關於 Xeljanz，我會請 Angela 發表評論，但只是初步評論 - Xeljanz 今年已經擁有 18 億美元。

So Xeljanz already have crossed the threshold, but it is quite important to be able to be stopped by exclusionary practices that maybe leaders can have in contracting.

所以 Xeljanz 已經跨過了門檻，但能夠被領導者可能在合同中可能擁有的排他性做法所阻止是非常重要的。

But I will ask Angela to comment on the growth prospects of Xeljanz in '19 and beyond.

但我會請 Angela 對 Xeljanz 在 19 年及以後的增長前景發表評論。

Sure.

當然。

So first of all, just beginning with '18, as Albert said, I mean, tremendous growth that we've seen in Xeljanz.

所以首先，正如阿爾伯特所說，從 18 年開始，我的意思是，我們在 Xeljanz 看到了巨大的增長。

37% growth Q4, over last year Q4 and particularly in the U.S., really strong double-digit growth, about 26%.

與去年第四季度相比，尤其是在美國，第四季度增長了 37%，兩位數的增長率非常強勁，約為 26%。

What we're seeing here in Xeljanz, and I'll start with the U.S., is really the mobilization of all of the indications for Xeljanz.

我們在 Xeljanz 看到的，我將從美國開始，實際上是 Xeljanz 的所有適應症的動員。

We see strong uptake for Xeljanz in rheumatoid arthritis and really great experience, and I think in comfort by rheumatologist in prescribing Xeljanz.

我們看到類風濕性關節炎患者對 Xeljanz 的強烈接受和非常好的經驗，我認為風濕病學家在開 Xeljanz 處方時感到安慰。

So just as an example, about 53% of U.S. patients now are using Xeljanz without methotrexate, so as monotherapy, which is just great progress in terms of, I think, demonstrating the confidence that rheumatologists have with Xeljanz.

因此，舉個例子，現在約有 53% 的美國患者正在使用不含甲氨蝶呤的 Xeljanz，作為單一療法，我認為這只是一個巨大的進步，證明了風濕病學家對 Xeljanz 的信心。

But what we also saw towards the end of last year was the launches of PsA and UC and another example here of the growth that we've experienced in terms of the Q4 volume growth, 1/3 of that volume growth came from these 2 new indications.

但我們在去年年底也看到了 PsA 和 UC 的推出，這是我們在第四季度銷量增長方面經歷的增長的另一個例子，1/3 的銷量增長來自這 2 個新產品適應症。

And just as another example of why we're excited about these new indications, in UC, specifically, our early data shows that we've also recently surpassed SIMPONI in terms of new patient market share.

作為我們為什麼對這些新適應症感到興奮的另一個例子，特別是在 UC 中，我們的早期數據顯示，我們最近在新患者市場份額方面也超過了 SIMPONI。

So I think in the U.S., we continue to see our tremendous growth possible across all of these indications.

所以我認為在美國，我們繼續看到我們在所有這些跡像中的巨大增長。

And as you know, we have other indications that are part of our life cycle management that we will be continuing to work on.

如您所知，我們還有其他跡象表明我們將繼續努力，這些跡像是我們生命週期管理的一部分。

Globally, we have launched RA, UC as well as PsA, but what we are in the middle of is gaining reimbursement for these new indications.

在全球範圍內，我們已經推出了 RA、UC 和 PsA，但我們正在為這些新適應症獲得報銷。

We're encouraged by recent signs from payers of their acceptance of Xeljanz in these new indications such as the NICE approval that we've got in 2018 for both UC and the PsA indications.

我們對付款人最近在這些新適應症中接受 Xeljanz 的跡象感到鼓舞，例如我們在 2018 年獲得 NICE 批准的 UC 和 PsA 適應症。

But net-net, when we sort of bring together all of these indications, RA, which is our base business, but now tagging on UC and PsA, we see between both of these 2 new indications a market that's approximately $10 billion large.

但是淨網，當我們將所有這些適應症，RA，這是我們的基礎業務，但現在標記在 UC 和 PsA 上時，我們看到在這兩個新適應症之間有一個大約 100 億美元的市場。

And I think, over time, with reimbursement, but also the increased comfort level and experience that rheumatologists, gastroenterologists will have with prescribing Xeljanz, we expect to see continued and strong growth from this franchise.

而且我認為，隨著時間的推移，隨著報銷，以及風濕病學家、胃腸病學家在開 Xeljanz 處方時的舒適度和經驗的增加，我們預計該特許經營權將持續強勁增長。

I think you also questioned about competitors as well, and certainly, this is a class that is hugely competitive.

我想你也質疑過競爭對手，當然，這是一個競爭非常激烈的課程。

But I think that Pfizer's long experience, and I think our track record of success in JAK science as well as our deeply entrenched in commercial footprint in rheumatology and now in gastroenterology will stand as well as we deal with this increased competition.

但我認為，輝瑞的長期經驗，我認為我們在 JAK 科學方面的成功記錄，以及我們在風濕病學和現在胃腸病學領域的商業足跡根深蒂固，將在我們應對日益激烈的競爭時站得住腳。

Thank you, Angela.

謝謝你，安吉拉。

And I will ask Frank to give us some numbers and comment on Emerging Markets.

我會請弗蘭克給我們一些數字並對新興市場發表評論。

Just an initial comment from my side, but the Emerging Markets is and will continue to be a key strength for us and a key pillar of growth and particularly, in the context of the new organization.

這只是我的初步評論，但新興市場現在並將繼續成為我們的關鍵力量和增長的關鍵支柱，特別是在新組織的背景下。

Let's not forget that a very big part of the Emerging Markets business has become part of the Upjohn Group.

我們不要忘記，新興市場業務的很大一部分已成為 Upjohn Group 的一部分。

And this is -- and this was exactly engineered so that we will be able to maximize the growth, and particularly in areas like Asia and particularly China where they have the biggest potential.

這是 - 這是經過精心設計的，以便我們能夠實現增長最大化，特別是在亞洲，尤其是中國等具有最大潛力的地區。

But Frank, why don't you give us some numbers to color the picture?

但是弗蘭克，你為什麼不給我們一些數字來給圖片上色呢？

Sure.

當然。

So Alex, Emerging Markets for the quarter, $3.3 billion in sales for the year, $12.65 billion in sales, each up 13% on an operational basis, strong performance.

因此，亞歷克斯，本季度新興市場銷售額為 33 億美元，銷售額為 126.5 億美元，在運營基礎上均增長 13%，表現強勁。

China, for the quarter and the year, more than 20% growth.

中國，本季度和全年增長超過 20%。

So you asked what to expect going forward?

所以你問未來會發生什麼？

We believe we can continue to grow Emerging Markets in the low double digits on going forward basis.

我們相信我們可以在未來的基礎上繼續以低兩位數的速度增長新興市場。

Your next question comes from Vamil Divan from Crédit Suisse.

你的下一個問題來自 Crédit Suisse 的 Vamil Divan。

So a couple if I could.

如果可以的話，一對夫婦。

So one, just around 2019 guidance, can you just elaborate a little bit more what you're assuming in terms of net price increases in the U.S. into that guidance and maybe just with all the discussions on a DC, what -- are there any significant changes that you're assuming may take place in the 2019 time frame?

所以，就在 2019 年左右的指導方針中，你能否再詳細說明一下你在美國淨價格上漲方面的假設，並將其納入該指導方針，也許只是關於 DC 的所有討論，有什麼 - 有什麼您假設在 2019 年的時間範圍內可能會發生重大變化？

And then just the second one is more on the oncology side, any update around when we might see some of the adjuvant breast cancer data from Ibrance?

然後只有第二個更多是關於腫瘤學方面的，關於我們什麼時候可以看到來自 Ibrance 的一些輔助乳腺癌數據的任何更新？

I know that's a key part of the next sort of part of the growth story for that franchise.

我知道這是該系列增長故事的下一個部分的關鍵部分。

So maybe you can share anything there.

所以也許你可以在那里分享任何東西。

And then similarly with BAVENCIO, which is more around the immuno-oncology adjuvant opportunity, it doesn't look like there's a lot of work being done with BAVENCIO there.

然後與 BAVENCIO 類似，它更多地圍繞免疫腫瘤佐劑機會，看起來那裡沒有用 BAVENCIO 做很多工作。

Maybe you can just comment on any adjuvant opportunity for that product.

也許您可以對該產品的任何輔助機會發表評論。

Right.

正確的。

On 2019 guidance and the pricing, I will ask again, Frank, to run some of the numbers.

關於 2019 年的指導和定價，弗蘭克，我會再次要求運行一些數字。

Sure.

當然。

So Vamil, in terms of price in the U.S. for 2019, we assume that price will be flat.

所以 Vamil，就 2019 年美國的價格而言，我們假設價格將持平。

And worldwide, we're assuming price that's in the negative low single digits.

在全球範圍內，我們假設價格處於負低個位數。

So minus low single digits and U.S, flat.

所以減去低個位數和美國，持平。

And I just want to make a comment here about it's very clear that pricing is not going to be a growth driver for us now and, I think, in the future.

我只想在這裡發表評論，很明顯定價不會成為我們現在和未來的增長動力。

It's very clear.

這很清楚。

So this is all included in our guidance and is also included in our projections for mid-single-digit growth post Lyrica LOE for the 5 years.

因此，這都包含在我們的指導中，也包含在我們對 Lyrica LOE 後 5 年中個位數增長的預測中。

And that will come from breakthrough medicines and based on volume rather than in price increases.

而這將來自突破性藥物，並基於數量而不是價格上漲。

And with that, the oncology question about Ibrance, let me pass it to Angela, please.

然後，關於 Ibrance 的腫瘤學問題，請讓我將其傳遞給 Angela。

Sure.

當然。

So we're really excited about the adjuvant opportunity.

所以我們對佐劑的機會感到非常興奮。

And as you said, it is the third part of our growth strategy, so a very important part of our growth story for Ibrance but also for oncology, in general.

正如你所說，這是我們增長戰略的第三部分，因此對於 Ibrance 和腫瘤學來說，這是我們增長故事中非常重要的一部分。

The 2 studies, PENELOPE and PALLAS, are the studies that we are looking forward to.

PENELOPE 和 PALLAS 這兩項研究是我們期待的研究。

Both of them are going well and have recruited faster than expected.

他們倆都進展順利，招聘速度比預期的要快。

And these studies are important because they give us the potential to double the number of patients that are eligible for Ibrance.

這些研究很重要，因為它們使我們有可能將符合 Ibrance 條件的患者數量增加一倍。

But we have to remember that these studies are event-driven and based on our projections, should read out some time next year.

但我們必須記住，這些研究是事件驅動的，並且基於我們的預測，應該在明年某個時候宣讀出來。

So I think more to come on that as we progress through the clinical trials.

因此，隨著我們在臨床試驗中取得進展，我認為還有更多的事情要做。

And then I think you had a second question on...

然後我想你有第二個問題......

BAVENCIO.

巴文西奧。

I think John maybe can take it, and then you can add, Angela.

我想 John 或許可以接受，然後 Angela，你可以補充。

Yes.

是的。

Thanks for the question, Vamil.

謝謝你的問題，瓦米爾。

So we are obviously continuing our effort with the execution of the avelumab development program.

因此，我們顯然正在繼續努力執行 avelumab 開發計劃。

It includes 30 ongoing studies, 7 of which are potentially registration enabling, involving more than 9,000 patients across 15 tumor types.

它包括 30 項正在進行的研究，其中 7 項有可能進行註冊，涉及 15 種腫瘤類型的 9,000 多名患者。

I think it's always important when we talk about IO to say that we have always recognized, believe that the real value of IO is expected to be in effective combinations.

我認為，當我們談論 IO 時，我們始終認識到並相信 IO 的真正價值在於有效的組合，這一點始終很重要。

And we believe that solid pre-clinical science, where we're in a good position to be competitive in a number of tumor types, it really underpins our development strategy.

我們相信，紮實的臨床前科學，使我們在多種腫瘤類型中處於有利地位，可以真正鞏固我們的發展戰略。

One example of that, I think Albert's already commented on is the JAVELIN Renal 101 trial combined, BAVENCIO with Inlyta in previously untreated advanced renal cell carcinoma patients and the combination provide a superior progression-free survival compared to SUTENT.

其中一個例子，我認為 Albert 已經評論過 JAVELIN Renal 101 試驗，BAVENCIO 與 Inlyta 在先前未治療的晚期腎細胞癌患者中聯合使用，與 SUTENT 相比，該組合提供了更好的無進展生存期。

There are 2 additional immunotherapy Phase 3 studies ongoing, including axitinib with pembrolizumab in first line renal cell carcinoma, which is a study sponsored by MSD and, also enzalutamide and atezolizumab and CRPC, which is sponsored by Genentech and Roche.

還有 2 項額外的免疫療法 3 期研究正在進行中，包括阿昔替尼聯合帕博利珠單抗治療一線腎細胞癌，這是一項由默沙東贊助的研究，還有恩雜魯胺和阿特珠單抗以及 CRPC，由基因泰克和羅氏贊助。

But I think in terms of the wider development program, which is kind of where you're driving, we're currently testing up to 10 Pfizer combinations with checkpoint inhibitors, including 5 targeted Pfizer therapies.

但我認為就更廣泛的開發計劃而言，這是你正在駕駛的地方，我們目前正在測試多達 10 種輝瑞與檢查點抑製劑的組合，包括 5 種靶向輝瑞療法。

We also have a number of studies combining avelumab and talazoparib across a range of indications.

我們還有許多研究將 avelumab 和 talazoparib 結合用於一系列適應症。

So that really speaks to just the way that we see BAVENCIO as being potentially valuable therapy in some important areas of high unmet need for patients where we believe combinations could really advance standard of care.

因此，這確實說明了我們認為 BAVENCIO 在一些重要的未滿足患者需求的重要領域具有潛在價值的治療方法，我們相信組合可以真正提高護理標準。

Your next question comes from Tim Anderson from Wolfe Research.

您的下一個問題來自 Wolfe Research 的 Tim Anderson。

I have a few questions.

我有幾個問題。

I don't want to put your cart before the horse on this but 2020 consensus has earnings growth being nearly flat.

我不想在這件事上本末倒置，但 2020 年的共識是收益增長幾乎持平。

There are a variety of pushes and pulls.

有多種推拉方式。

You're launching new products.

您正在推出新產品。

You have some strong growing in-line brands, but you still have Lyrica, LOE spilling over into 2020.

你有一些增長強勁的在線品牌，但你仍然有 Lyrica 和 LOE 溢出到 2020 年。

I'm wondering if you can comment on how you kind of view where consensus sits on the earnings line.

我想知道你是否可以評論一下你如何看待共識在收益線上的位置。

Is 2020 likely to be a flattish year as well?

2020 年也可能是平淡的一年嗎？

Second question is on this other income deductions line.

第二個問題是關於其他收入扣除額。

Just wondering why the change in heart in how you account for the impact of unrealized and realized gains and losses, why different in 2019 versus 2018?

只是想知道為什麼您對未實現和已實現損益的影響的解釋方式發生了變化，為什麼 2019 年與 2018 年有所不同？

Was that at the advice of your accountants or the IRS or someone else?

那是你的會計師或美國國稅局或其他人的建議嗎？

And then last question, on the JAK1 inhibitor for atopic derm, you have a Phase 3 reading out 2019.

然後是最後一個問題，關於特應性皮膚的 JAK1 抑製劑，您有 2019 年的第 3 階段讀數。

Can we assume you'll need 2 Phase 3s for approval in that indication, and when will the second one read out if it does require 2?

我們是否可以假設您需要 2 個 Phase 3s 才能獲得該適應症的批准，如果第二個階段確實需要 2 個，什麼時候會讀出？

Thank you.

謝謝。

Frank, why don't you deal with the question about the consensus and the OID, and then Mikael can discuss the JAK1 Phase 3 study.

Frank，你為什麼不處理關於共識和 OID 的問題，然後 Mikael 可以討論 JAK1 3 期研究。

Sure.

當然。

So first, Tim, on the OID question, now that was my decision in terms of taking the gain or loss on equity securities, equity investments out of adjusted income.

因此，首先，蒂姆，關於 OID 問題，現在這是我的決定，即從調整後的收入中扣除股權證券、股權投資的收益或損失。

New accounting was put in place on this on the beginning of 2018 in terms of realizing or booking gains and unrealized gains into results.

2018 年初，在實現或記賬收益和未實現收益方面，新會計已到位。

The amount of -- the size of the gains in 2018 surprised us quite frankly, introduced a lot of volatility into our numbers.

坦率地說，2018 年的收益規模讓我們感到驚訝，給我們的數字帶來了很大的波動。

So I decided at the beginning of 1/1/19, we'll take that out.

所以我決定在 2019 年 1 月 1 日開始，我們將把它去掉。

And by the way, please note, I actually think that if we left it in, that the probability of that being a good guy is much higher than if it were a bad guy to our 2019 results, but I thought the best thing to do was just take it out because it was introducing a level of volatility that isn't part of our core business.

順便說一句，請注意，我實際上認為，如果我們保留它，那麼對於我們 2019 年的結果來說，它成為好人的可能性要比它成為壞人的可能性高得多，但我認為最好的辦法只是把它去掉，因為它引入了不屬於我們核心業務一部分的波動性。

So we removed it for that reason.

所以我們出於這個原因刪除了它。

But we tried to show that on the guidance figures that we've provided to you all in our release at the bottom of Page #2.

但我們試圖在我們在第 2 頁底部的新聞稿中向大家提供的指導數據中證明這一點。

Then in terms of the 2020 numbers, and I won't comment on consensus, obviously, but in terms of our rhythm of the numbers.

然後就 2020 年的數字而言，顯然我不會對共識發表評論，但就我們的數字節奏而言。

For job one is we got to deliver on what we've just said for 2019.

對於工作之一，我們必須兌現我們剛剛所說的 2019 年目標。

2020, we will still have the challenge of Lyrica LOE.

2020年，我們依然有Lyrica LOE的挑戰。

We get the full year effect of that in 2000 -- in 2020, so we'll have to work our way through that relative to the business, and obviously, we do everything we can to work our way through that relative to earnings.

我們在 2000 年 - 2020 年得到了全年的影響，所以我們必須努力解決與業務相關的問題，顯然，我們會盡一切努力解決與收益相關的問題。

Thank you, Frank.

謝謝你，弗蘭克。

Mikael, what about the JAK1, how many Phase 3 studies do we need?

Mikael，JAK1 怎麼樣，我們需要多少個 Phase 3 研究？

So I would say it like this.

所以我會這樣說。

We think it's very large opportunity for the JAK1 in atopic dermatitis, and we're very excited about the profile as you remember from our Phase 2 studies that this drug class seems to have real rapid activity, both in clearing skin eczema and in pruritus itching.

我們認為 JAK1 在特應性皮炎中有很大的機會，我們對您從我們的 2 期研究中記得的概況感到非常興奮，這種藥物類別似乎在清除皮膚濕疹和瘙癢方面具有真正的快速活性.

We have actually 2 trials reading out in 2019, one in May and one in September range, give or take, with some time as these trials conclude.

實際上，我們在 2019 年有 2 項試驗宣讀，一項在 5 月，一項在 9 月範圍內，或多或少，這些試驗結束時還有一段時間。

And we actually have a significant program here to potentially establish these as a very significant product with also trials reading out in 2020, including a comparator trial to the [peak's end] and I think particular there is to look at the rapid onset of JAK versus biologicals.

實際上，我們這裡有一個重要的計劃，有可能將這些確定為一個非常重要的產品，並在 2020 年進行試驗，包括對 [峰值結束] 的比較試驗，我認為特別要看看 JAK 與生物製品。

There is a mechanism of action started to provide additional insight and also a 52 weeks longer-term studies.

有一種行動機制開始提供額外的見解，還有一項為期 52 週的長期研究。

So it's a very comprehensive data package.

所以這是一個非常全面的數據包。

But please look out for our 2019 data readout that would tell us the initial outcome of this exciting new drug class.

但請注意我們 2019 年的數據讀數，它將告訴我們這一令人興奮的新藥類別的初步結果。

The strength of the profile as it will emerge.

個人資料的強度，因為它將出現。

Your next question comes from Louise Chen from Cantor Fitzgerald.

你的下一個問題來自 Cantor Fitzgerald 的 Louise Chen。

So first question I had was on tanezumab.

所以我的第一個問題是關於 tanezumab。

Do you think the RPOA and the other safety imbalances are result of the drug or the patient population?

您認為 RPOA 和其他安全失衡是藥物還是患者群體的結果？

And then second question I had was if you could provide any sort of efficacy data with respect to the 2 arms?

然後我的第二個問題是你是否可以提供關於這兩個手臂的任何類型的療效數據？

Or if you can't, how does it compare to what we saw on 16-week data?

或者如果你不能，它與我們在 16 週數據中看到的相比如何？

And then last question I had was just on your leverage as you move past these LOEs, what kind of leverage can we assume to the bottom line?

然後我的最後一個問題只是關於你在超越這些 LOE 時的槓桿作用，我們可以假設什麼樣的槓桿作用到底線？

And how much better will it be than what we see now?

它會比我們現在看到的好多少？

Mikael, can you please deal with the tanezumab question, please?

Mikael，你能解決一下 tanezumab 問題嗎？

Yes.

是的。

I mean, certainly, we known from historical trials that patients with advanced OA are more likely to develop RPOA than patients with chronic lower back pain that, in general, have healthier joints.

我的意思是，當然，我們從歷史試驗中得知，患有晚期 OA 的患者比患有慢性腰痛的患者更有可能患上 RPOA，而慢性腰痛患者的關節通常更健康。

That's #1.

那是#1。

#2, about tanezumab relationship to this, I think we will get a better understanding as we see this year the comparator trial with NSAIDs for OA and with opioids in chronic lower back pain.

#2，關於 tanezumab 與此的關係，我認為我們會更好地理解，因為我們今年看到了 NSAIDs 治療 OA 和阿片類藥物治療慢性腰痛的比較試驗。

That will allow us to understand the incidence of RPOA on different treatment, but please let me just underline each drug class has its profile.

這將使我們能夠了解 RPOA 在不同治療中的發生率，但請讓我強調每種藥物類別都有其概況。

And of course, opioid, as you know, which is the major comparator for us in chronic lower back pain are associated with a range of very difficult side effects, including fatal outcome for tens of thousands Americans every year, very different from low single-digit orthopedic injury that we have discussed.

當然，如您所知，阿片類藥物是我們治療慢性腰痛的主要對照藥物，它與一系列非常困難的副作用相關，包括每年導致數万美國人死亡的後果，這與低單-我們已經討論過的手指骨科損傷。

And let me even remind you that NSAIDs which, in general, has been not very effective on advanced OA are, of course, associated with gastrointestinal risks of bleeding and also been associated with cardiovascular risk.

讓我什至提醒您，一般而言，非甾體抗炎藥對晚期 OA 不是很有效，當然，它與胃腸道出血風險相關，也與心血管風險相關。

So overall, we think that tanezumab represent a new emerging drug class with a very interesting efficacy, and we'll learn more about the exact tolerability safety profile later this year, but we remain very positive about this offering for patient pending of course finalization of studies and potential regulatory process.

因此，總的來說，我們認為 tanezumab 代表了一種具有非常有趣療效的新興藥物類別，我們將在今年晚些時候了解更多關於確切的耐受性安全概況的信息，但我們對這種為患者提供的產品仍然非常樂觀，當然還有待最終確定研究和潛在的監管程序。

Thank you, Mikael.

謝謝你，米凱爾。

And as regards to the levers of the bottom line, let me ask the master of levers, Frank D'Amelio, to comment.

至於底線的槓桿，讓我請槓桿大師Frank D'Amelio發表評論。

So Louise, here's how I think about this and to kind of connect back to Tim's question, we need to work our way through 2019.

所以 Louise，我是這樣想的，為了回到 Tim 的問題，我們需要努力度過 2019 年。

We need to work our way through 2020, work our way through the Lyrica LOE and the major impact of the Lyrica LOE in those 2 periods.

我們需要努力度過 2020 年，努力度過 Lyrica LOE 以及 Lyrica LOE 在這兩個時期的主要影響。

We get to 2021, LOEs decline materially.

到了 2021 年，LOE 大幅下降。

Our pipelines kicking in, our in-line products are kicking in, our emerging markets are continuing to grow, that's where we see this inflection point in terms of the rhythm of the business, the rhythm of the numbers.

我們的管道投入使用，我們的在線產品投入使用，我們的新興市場正在繼續增長，這就是我們在業務節奏和數字節奏方面看到這個拐點的地方。

We think we can grow that top line mid-single digits.

我們認為我們可以將收入增長到中個位數。

So approximately 5%.

所以大約5%。

We think, clearly, we can grow the top line when we grow the top line mid-single digits.

我們認為，很明顯，當我們將收入增長到中個位數時，我們就可以增長收入。

We can clearly grow the bottom line more than mid-single digits.

我們顯然可以將底線增長超過中個位數。

And hopefully, our actions over the years have demonstrated our ability to do that.

希望我們多年來的行動已經證明我們有能力做到這一點。

So that's how I think about this in terms of rhythm of the business.

所以這就是我在業務節奏方面的想法。

Well said, Frank.

說得好，弗蘭克。

Your next question comes from David Risinger from Morgan Stanley.

你的下一個問題來自摩根士丹利的 David Risinger。

Just a follow-up on 2020.

只是 2020 年的後續行動。

So obviously, the patent expiration of Lyrica annualizes in June of 2020, so do you think that Pfizer can return to revenue growth in the second half of 2020 after that annualizes, Frank?

很明顯，Lyrica 的專利在 2020 年 6 月年化後到期，那麼您認為輝瑞（Pfizer）在年化後能否在 2020 年下半年恢復收入增長，弗蘭克？

Or are there other factors that could preclude or return to growth in that second half period?

還是有其他因素可以阻止或恢復下半年的增長？

And then with respect to Ibrance, I was just hoping for some perspective on what we should expect for U.S. sales in 2019 relative to 2018.

然後關於 Ibrance，我只是希望就我們對 2019 年美國銷售額相對於 2018 年的預期有一些看法。

Obviously, sales have been flattening out according to the IMS data.

顯然，根據 IMS 數據，銷售額一直在趨於平穩。

But should we be expecting U.S. sales to be flat in '19 versus '18?

但我們是否應該期望美國 19 年的銷售額與 18 年持平？

Or could they be down slightly due to competition gaining share?

或者他們會因為競爭獲得份額而略有下降嗎？

Any color would be helpful.

任何顏色都會有幫助。

Thank you.

謝謝。

And obviously, we do not provide guidance for the year after.

顯然，我們不會為後一年提供指導。

And also, we do not comment, provide guidance on individual products, particularly on individual reason of an individual product.

而且，我們不對個別產品發表評論，提供指導，特別是針對個別產品的個別原因。

But I'll ask Frank to give some color on the 2020 and what happens after the second quarter, and then, of course, Angela, to give at least the dynamics of the market.

但我會請 Frank 對 2020 年以及第二季度之後發生的事情給出一些看法，然後，當然，Angela，至少要給出市場的動態。

So Dave, I'll do my best to try to answer this, but to Albert's point, trying to provide 2020 guidance and breaking it down into quarters and halves is extremely difficult.

所以戴夫，我會盡力回答這個問題，但就阿爾伯特的觀點而言，試圖提供 2020 年指導並將其分解為四分之一和兩半是極其困難的。

What I would say is this, there will still be material LOE impacts from Lyrica in 2020.

我要說的是，2020 年 Lyrica 仍將對 LOE 產生重大影響。

And so we still view 2020 as a challenging year.

因此，我們仍然將 2020 年視為充滿挑戰的一年。

I think the real pivot point, the real inflection point becomes 2021 using 2020 as the base year.

我認為真正的支點，真正的拐點是 2021 年，以 2020 年為基準年。

And that's where I think we can really show some major-league progress on the top line and then dropping that to the bottom.

這就是我認為我們真正可以在頂線展示一些大聯盟進步然後將其降至底部的地方。

I'm going into quarter-after-quarter, of course.

當然，我將逐季進行。

It's just something that we don't want to speculate on.

這只是我們不想推測的事情。

And Angela?

還有安吉拉？

So I think as we think about Ibrance in the U.S. certainly, we have been very pleased with the performance of Ibrance to date.

所以我認為，當我們考慮美國的 Ibrance 時，我們對 Ibrance 迄今為止的表現非常滿意。

I mean, just really strong growth quarter-over-quarter or even full year over full year, but the way we look at it, in the 3 phases of growth is how we think about its growth prospects.

我的意思是，季度環比增長甚至全年增長都非常強勁，但我們看待它的方式是，在三個增長階段，我們是如何看待它的增長前景的。

So Phase 1 is this U.S. launch in metastatic breast cancer, which includes our growth of the CDK class as well as our own leadership of that class.

因此，第 1 階段是在美國推出的轉移性乳腺癌，其中包括我們 CDK 類的增長以及我們自己在該類中的領導地位。

And in this regard, being that we had such rapid uptake initially, we have now reached a 50% class share, which we're very pleased with though we know that this is the point that we will need to continue to expand on in order to generate the growth.

在這方面，由於我們最初的吸收速度如此之快，我們現在已經達到了 50% 的班級份額，我們對此感到非常高興，儘管我們知道這是我們需要繼續擴展的重點，以便產生增長。

But certainly, the fact that we've been able to treat 95,000 patients in the U.S. with metastatic breast cancer is very positive for us.

但可以肯定的是，我們已經能夠在美國治療 95,000 名轉移性乳腺癌患者這一事實對我們來說是非常積極的。

And then in the other phase of our growth is our international launches, which really began in 2018.

然後在我們增長的另一個階段是我們的國際發布，它真正開始於 2018 年。

And here, we've exceeded our expectations as well.

在這裡，我們也超出了我們的預期。

We have treated more than 85,000 patients ex U.S. through the launches in Japan, in the EU, in China and Brazil towards the end of last year.

截至去年年底，通過在日本、歐盟、中國和巴西的上市，我們已經治療了美國以外的 85,000 多名患者。

So I think in 2019, that's going to be another focus area of growth for us.

所以我認為在 2019 年，這將成為我們增長的另一個重點領域。

And then Phase 3, we talked about already a little bit earlier, which is our adjuvant population, which is coming up.

然後是第 3 階段，我們之前已經談過，即將到來的是我們的佐劑人群。

But maybe sort of coming back to the U.S. and specifically where the growth is coming from, we do see the class growth at 50% as one that -- as one where additional opportunities can be found.

但也許有點回到美國，特別是增長來自哪裡，我們確實看到 50% 的班級增長——作為一個可以找到更多機會的地方。

And I think that what we are now focused on is breaking the entrenchment with the single agent endocrine therapy, which will then allow us to grow the CDK class.

我認為我們現在關注的是打破單一藥物內分泌治療的壁壘，這將使我們能夠發展 CDK 類。

But we're also clear about what it is that we need to do here.

但我們也很清楚我們需要在這裡做什麼。

So just as an example, we know that 25% of our key accounts have more than 40% share in the single-agent endocrine therapy.

因此，舉個例子，我們知道我們 25% 的主要客戶在單劑內分泌治療中佔有超過 40% 的份額。

So we're really focused on targeting our HCP education very carefully in this area.

因此，我們真正專注於在這一領域非常謹慎地針對我們的 HCP 教育。

We also know that educating a newly diagnosed HR+/ HER2- patients about the significant clinical benefits of adding Ibrance to -- in first line therapy is an important aspect of our work.

我們還知道，教育新診斷的 HR+/HER2-患者了解將 Ibrance 添加到一線治療中的顯著臨床益處是我們工作的一個重要方面。

And here, we know that the data show that in the first line setting, when you add Ibrance to endocrine therapy, you achieve a longer progression-free survival of about 12 months.

在這裡，我們知道數據顯示，在一線設置中，當您將 Ibrance 加入內分泌治療時，您可以實現約 12 個月的更長無進展生存期。

So we think that this is really important information for patients to have.

所以我們認為這對患者來說是非常重要的信息。

So when you look at the totality of our data, our access, our strong leadership position, but also the strategy that we have, we believe that we can really make a difference from a patient impact perspective, and we see great potential for growth for Ibrance.

因此，當您查看我們的全部數據、我們的訪問權限、我們強大的領導地位以及我們擁有的戰略時，我們相信我們可以從患者影響的角度真正發揮作用，並且我們看到了巨大的增長潛力Ibrance。

Your next question comes from Jason Gerberry from Bank of America.

你的下一個問題來自美國銀行的 Jason Gerberry。

I guess, just -- I'm not sure that you'll be able to answer this, but just on tanezumab.

我想，只是 - 我不確定你是否能夠回答這個問題，但只是關於 tanezumab。

Was there any sort of dose response with respect to the RPOA rate?

關於 RPOA 率是否存在任何類型的劑量反應？

I believe in the prior study at ACR, there was a bit of a dose-related response.

我相信在 ACR 之前的研究中，有一些與劑量相關的反應。

So I was just curious to what extent you can comment on that.

所以我很好奇你可以在多大程度上對此發表評論。

And then also just with the RPOA, did -- I know there's an additional dose that was provided in this trial versus prior trials, so just sort of curious if the inclusion of an additional dose if events were skewed early or late in the treatment period.

然後還有 RPOA，確實 - 我知道在這個試驗中提供了額外的劑量與之前的試驗相比，所以有點好奇如果事件在治療期的早期或晚期出現偏差，是否包括額外的劑量.

And then one housecleaning item.

然後是一件大掃除物品。

Do you expect to be in the market for Rituxan at time of market formation, which is, I think, the Street's thinking around mid to second half of 2019?

您是否期望在市場形成時進入 Rituxan 市場，我認為這是華爾街在 2019 年中下半年左右的想法？

Mikael, do you want to take the tanezumab question?

Mikael，你想回答 tanezumab 的問題嗎？

Thank you for the interest in the product.

感謝您對產品的關注。

And as we have said previously, we were very pleased with the readout of 1057 and 1056.

正如我們之前所說，我們對 1057 和 1056 的讀數非常滿意。

More than 1,000 patients with robust efficacy we reported on the 5-milligram plus across 3 primary endpoint and on 2 of them on 2.5-milligram.

我們報告了超過 1,000 名患者在 5 毫克以上的 3 個主要終點和其中 2 名患者的 2.5 毫克劑量方面具有強大療效。

We have not seen on these 2 doses any difference in the tolerability or safety profile and feel that we understand the profile very well.

我們沒有發現這 2 種劑量在耐受性或安全性方面有任何差異，並且認為我們非常了解這些情況。

And we're also pleased to report that total joint replacement was similar versus placebo.

我們也很高興地報告，全關節置換與安慰劑相似。

So I think that speaks to the strength of the data set we have.

所以我認為這說明了我們擁有的數據集的實力。

And we look forward to share data in more details at upcoming conference and report out additional studies this year.

我們期待在即將召開的會議上更詳細地分享數據，並在今年報告更多研究。

Yes, very nice interest on tanezumab over here.

是的，對這裡的 tanezumab 非常感興趣。

Angela, about the biosimilar, Rituxan?

Angela，關於生物仿製藥，Rituxan？

So our plans are on track, and we are planning to launch Rituxan in 2019, and we look forward to receiving the approvals and then planning for our launch.

所以我們的計劃正在按計劃進行，我們計劃在 2019 年推出 Rituxan，我們期待獲得批准，然後計劃我們的推出。

Your next question comes from Geoff Meacham from Barclays.

你的下一個問題來自巴克萊銀行的 Geoff Meacham。

Sorry to ask another one on the 2019, 2020 growth profile.

抱歉再問一個關於 2019 年、2020 年增長概況的問題。

But Albert, is there a willingness to be more active on commercial stage M&A just to change the growth profile until 2021 or even divesting lower growth franchises?

但是艾伯特，是否願意在商業階段的併購中更加活躍，只是為了改變 2021 年之前的增長狀況，甚至剝離增長較低的特許經營權？

I'm just trying to see how proactive Pfizer will be versus just waiting until after the Lyrica LOE.

我只是想看看輝瑞公司將如何積極主動，而不是等到 Lyrica LOE 之後。

And then another one on biosimilars, there's obviously lots of launches coming up, including Rituxan.

然後是另一個關於生物仿製藥的產品，顯然有很多產品即將推出，包括 Rituxan。

How will the strategy evolve from a pricing and access perspective and what are the main lessons you guys have learned so far from Inflectra just of late that could help accelerate the launches?

從定價和訪問的角度來看，該戰略將如何演變？你們最近從 Inflectra 中學到的有助於加速發布的主要經驗教訓是什麼？

Angela will answer in a moment with biosimilars question about our -- that you asked, pricing and what is our strategy there.

安吉拉馬上會回答關於我們的生物仿製藥問題——你問過的，定價以及我們在那裡的戰略是什麼。

But look, on '19 and '20, as I said, we will be proactive, but proactive doesn't mean that our focus it is how to change the profile of '19.

但是，正如我所說，在 19 和 20 年，我們會積極主動，但主動並不意味著我們的重點是如何改變 19 年的形象。

Proactive means how we're going to enhance the growth profile of Pfizer in the pivotal moment that is happening after the June-July of 2020, or in '21, we will see this a full year.

積極主動意味著我們將如何在 2020 年 6 月至 7 月或 21 年之後的關鍵時刻增強輝瑞的增長狀況，我們將看到這一整年。

So in the commercial space, again, we are looking for opportunities with our -- to deploy capital that will help, but the direction right now, it is to enhance our growth profile and not to dilute it.

因此，在商業領域，我們再次尋找機會 - 部署有幫助的資本，但目前的方向是提高我們的增長狀況，而不是稀釋它。

And the direction right now, it is not to disturb operationally the business in this very critical phase that we are trying to get the pipeline through the finish line, prepare the markets commercially and then launch the products.

而現在的方向是，在這個非常關鍵的階段，我們正在努力讓管道通過終點線，在商業上準備市場，然後推出產品，而不是在運營上乾擾業務。

And this is the focus, really.

這才是重點，真的。

Angela, what about biosimilars?

安吉拉，生物仿製藥怎麼樣？

So we are looking forward to the launch of 3 additional oncology biosimilars in our portfolio in 2019.

因此，我們期待 2019 年在我們的產品組合中推出 3 種額外的腫瘤生物仿製藥。

And I think that what we've learned about the biosimilar market is that there, it is a -- we believe in it and -- from a potential perspective and from a growth perspective.

而且我認為我們對生物仿製藥市場的了解是，它是一個 - 我們相信它 - 從潛在的角度和增長的角度來看。

What we're also seeing are differences in the EU and in the U.S. So in the EU, we see a very rapid uptake and actually great acceptance of biosimilars.

我們還看到了歐盟和美國的差異。因此，在歐盟，我們看到生物仿製藥的採用非常迅速，實際上也得到了極大的接受。

And if I just use infliximab molecule as an example, the infliximab biosimilars are about 65% of the total molecule.

如果我僅以英夫利昔單抗分子為例，英夫利昔單抗生物仿製藥約佔總分子的 65%。

And we've seen rapid uptake and great acceptance by customers, by payers.

我們已經看到客戶和付款人的快速採用和高度接受。

We see a market that, I think, is evolving and developing in the U.S. and I think that our experience with infliximab in the U.S. really is not a great analogy for what might be to come with our new oncology biosimilars.

我們看到一個市場，我認為，在美國正在發展和發展，我認為我們在美國使用英夫利昔單抗的經驗確實不能很好地類比我們新的腫瘤生物仿製藥可能帶來的結果。

Just because they're very different dynamics in the I&I space compared to the oncology space.

只是因為與腫瘤學領域相比，它們在 I&I 領域的動態非常不同。

The big difference in the I&I space in the U.S. is the exclusionary contracting from J&J, which has really prevented and been a great impediment to our ability to grow the I&I biosimilar.

美國 I&I 領域的最大差異是強生的排他性合同，這確實阻礙了我們發展 I&I 生物仿製藥的能力，並且是一個很大的障礙。

Rebates, rather than net price has really driven, I think, formulary access, and that has been a great barrier to our ability to grow.

回扣，而不是淨價，我認為真正推動了處方准入，這一直是我們發展能力的巨大障礙。

However, we see different dynamics in the oncology space, and that is because oncology drugs are shorter in duration of therapy.

然而，我們在腫瘤領域看到了不同的動態，這是因為腫瘤藥物的治療持續時間較短。

So that allows new patients to turn over faster.

這樣可以讓新患者更快地轉身。

And it will make it easier for the physicians to initiate new patients on oncology biosimilars.

這將使醫生更容易讓新患者接受腫瘤生物仿製藥。

And we believe that this will enable customers to benefit from the cost savings that they can derive from biosimilars much more quickly than what you might see in the I&I space where the duration of therapy is very long.

我們相信，這將使客戶能夠從生物仿製藥中節省的成本中受益，這比您在治療持續時間很長的 I&I 領域看到的要快得多。

It's a long chronic disease.

這是一種長期的慢性疾病。

So we are excited about the upcoming launches of our oncology biosimilars, and we expect our entire biosimilar portfolio to be a strong contributor to growth to Pfizer in 2019.

因此，我們對即將推出的腫瘤生物仿製藥感到興奮，我們預計我們的整個生物仿製藥產品組合將在 2019 年為輝瑞的增長做出強大貢獻。

Thank you, Angela.

謝謝你，安吉拉。

Thanks for the insights.

感謝您的見解。

And we'll take your last question please, operator.

接線員，我們將回答您的最後一個問題。

Your final question comes from Seamus Fernandez from Guggenheim.

你的最後一個問題來自古根海姆的 Seamus Fernandez。

So my question really was on tanezumab.

所以我的問題真的是關於 tanezumab。

I know there's been a lot of questions around the safety side, but the low dose didn't separate from placebo on one of the co-primary endpoints.

我知道圍繞安全方面存在很多問題，但低劑量並沒有在共同主要終點之一上與安慰劑區分開來。

And just wanted to understand a little bit better how you guys are feeling about the differences in this particular patient population to really give you strong convictions that the assumed benefit of efficacy of this novel mechanism are going to be sustained.

只是想更好地了解你們對這個特定患者群體的差異有何看法，以真正讓你們堅信這種新機制的假定功效效益將得以持續。

Mikael?

米凱爾？

Thank you.

謝謝。

First, let me point out that the 5-milligram dose in 1056 and 1057 performed very well, consistent, robust on all 3 primary endpoints in both the studies.

首先，讓我指出，1056 和 1057 中的 5 毫克劑量在兩項研究的所有 3 個主要終點上表現非常好、一致、穩健。

The 2.5-milligram performed with statistical significance in 1056 on all 3 primary endpoint.

2.5 毫克在 1056 年的所有 3 個主要終點上均具有統計學意義。

And on the 2 most important, it was positive, pain and physical function.

在最重要的兩個方面，它是積極的，疼痛和身體機能。

It was positive on overall assessment of OA at several time points, but narrowly missed at the 24 week.

在幾個時間點對 OA 的總體評估呈陽性，但在第 24 週時差一點。

Often what happens in this type of trials in pain is that you may have variability in placebo response at various time points that is likely to influence.

通常在這種類型的疼痛試驗中發生的情況是，您可能會在不同時間點對安慰劑反應產生差異，這可能會產生影響。

But please note that numerically, we are still pleased with the response to 2.5 milligram at all time points.

但請注意，在數字上，我們仍然對所有時間點對 2.5 毫克的反應感到滿意。

And we think we have 2 doses that offer, so far, robust consistent efficacy and very advanced patient populations.

我們認為，到目前為止，我們有 2 種劑量可提供穩健一致的療效和非常先進的患者群體。

And we feel that we consistently have reported the tolerability and safety profile.

我們覺得我們一直在報告耐受性和安全性。

So we look forward to conclude the trials with another osteoarthritis later this spring and a chronic lower back pain and so far, we are very pleased with tanezumab.

因此，我們期待在今年春天晚些時候結束對另一種骨關節炎和慢性腰痛的試驗，到目前為止，我們對 tanezumab 非常滿意。

Thank you, Mikael, and just thank you, everyone, for your great questions.

謝謝 Mikael，也謝謝大家提出的重要問題。

I was very pleased to see that the majority of the focus right now is on our pipeline.

我很高興看到現在大部分注意力都集中在我們的管道上。

And I think you're right.

我認為你是對的。

This is where it should be.

這是它應該在的地方。

And we are looking forward for equally great '19 as we had in 2018.

我們期待與 2018 年一樣出色的 19 年。

Chuck?

查克？

Great.

偉大的。

Thank you, everybody, for your attention this morning.

謝謝大家今天早上的關注。

This will end the call.

這將結束通話。

Ladies and gentlemen, this does conclude Pfizer's fourth quarter 2018 earnings conference call.

女士們，先生們，輝瑞公司 2018 年第四季度財報電話會議到此結束。

Thank you for your participation.

感謝您的參與。

You may now disconnect.

您現在可以斷開連接。