美國安進 (AMGN) 2019 Q1 法說會逐字稿

My name is Ian, and I will be your conference facilitator today for Amgen's First Quarter 2019 Financial Results Conference Call. (Operator Instructions)

我叫伊恩，今天我將擔任安進公司 2019 年第一季財務業績電話會議的主持人。（操作說明）

I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin.

現在我謹向大家介紹投資人關係副總裁 Arvind Sood。蘇德先生，您可以開始了。

Okay. Thanks, Ian. Good afternoon, everybody. Thanks for joining us today on our first quarter call. Special welcome to those who are new in their coverage of our company, including Jay Olson of Oppenheimer, Yaron Werber of Cowen and Do Kim of BMO.

好的。謝謝你，伊恩。大家下午好。感謝您今天參加我們第一季財報電話會議。特別歡迎那些首次報導我們公司的媒體，包括 Oppenheimer 的 Jay Olson、Cowen 的 Yaron Werber 和 BMO 的 Do Kim。

So we go into 2019 having put in place a strong track record of execution, and we are well prepared for the challenges and opportunities ahead. I am joined today by our Chairman and CEO, Bob Bradway, who will provide a strategic overview of our business and the environment we operate in. After Bob's comments, our CFO, David Meline, will review our financial results for the first quarter. Our Head of Global Commercial Operations, Murdo Gordon, will then review our product performance, followed by our Head of R&D, Dave Reese, who will provide a pipeline update.

因此，我們帶著良好的執行記錄進入 2019 年，並且我們已經為未來的挑戰和機會做好了充分的準備。今天，我們的董事長兼執行長鮑伯‧布拉德韋先生將與我一同為大家帶來我們業務及我們所處環境的策略概述。在鮑伯發言之後，我們的財務長大衛梅林將審查我們第一季的財務業績。接下來，我們的全球商業營運主管 Murdo Gordon 將回顧我們的產品表現，隨後是我們的研發主管 Dave Reese，他將提供產品線更新資訊。

We will use slides to guide our discussion today, and you should have received the link separately. Just a reminder that we will use non-GAAP financial measures in today's presentation, and some of the statements will be forward-looking statements. Our 10-K and subsequent filings identify factors that could cause our actual results to differ materially.

今天我們將使用幻燈片來引導討論，您應該已經單獨收到連結了。提醒各位，我們今天的演示將使用非GAAP財務指標，其中一些陳述屬於前瞻性陳述。我們的 10-K 及後續文件列出了可能導致我們實際業績與預期有重大差異的因素。

So with that, I would like to turn the call over to Bob. Bob?

那麼，接下來我將把電話交給鮑伯。鮑伯？

Okay. Thank you, Arvind, and let me add to Arvind's welcome to all of you joining the call today. We enter 2019 with a strong track record of execution and an improved ability to innovate, compete and grow over the long term. We feel now well positioned to capitalize on the growth opportunities presented by our newer products in our pipeline even as we effectively defend our mature products against emerging and expected new competition. As you know, drug prices are being challenged around the world, and we, therefore, have said for some time that we expect volume-driven growth to be important to our long-term success. And in Q1, we once again demonstrated our ability to grow unit volumes, especially for our newer products like Prolia, Repatha, Aimovig as well as for of our 6 hematology/oncology products that are in early phases of their life cycle.

好的。謝謝 Arvind，我也要代表 Arvind，歡迎今天所有參加電話會議的朋友們。進入 2019 年，我們擁有良好的執行記錄，並且具備更強的創新、競爭和長期發展能力。我們現在感覺已經做好了充分準備，能夠抓住我們研發管線中的新產品所帶來的成長機會，同時有效地保護我們的成熟產品免受新興和預期中的新競爭的影響。如您所知，世界各地的藥品價格都面臨著挑戰​​，因此，我們一直以來都表示，我們預計銷售驅動型成長對我們的長期成功至關重要。在第一季度，我們再次證明了我們提升銷售的能力，特別是對於我們的新產品，如 Prolia、Repatha、Aimovig，以及我們 6 款處於生命週期早期階段的血液/腫瘤產品。

I believe our performance outside of the U.S., where we have faced biosimilar competition for over a decade, is instructive. There, our business generated 15% unit volume growth in the first quarter as growth of our newer products more than offset the erosion of our mature brands and biosimilar competition. We remain confident in the life cycle management strategies we have in place to defend our mature brands, and we believe there is considerable upside potential with our newer products that will drive attractive long-term growth.

我認為我們在美國以外的地區（我們在那裡面臨生物相似藥競爭超過十年）的表現具有指導意義。在第一季度，我們的業務實現了 15% 的銷售成長，這主要得益於新產品的成長，其成長超過了成熟品牌銷售下滑和生物相似藥競爭的影響。我們對現有的生命週期管理策略充滿信心，這些策略能夠保護我們成熟的品牌，並且我們相信，我們的新產品具有相當大的成長潛力，能夠推動長期的良好成長。

As a leader in bone health with Prolia, we know that there's a need for additional innovative therapy for women who are at high risk for fracture from postmenopausal osteoporosis. In Q1, we added EVENITY to our portfolio of first-in-class innovative medicines with approvals in Japan and earlier this month in the U.S. Postmenopausal osteoporosis remains a highly underdiagnosed and undertreated disease, with potentially devastating consequences from fractures, many of which are predictable and preventable. And we're excited to be at the forefront of offering innovative products to the millions of women worldwide who may benefit from them.

身為骨骼健康領域的領導者，我們憑藉 Prolia 產品深知，對於患有停經後骨質疏鬆症、骨折風險較高的女性來說，還需要更多創新療法。第一季度，我們將 EVENITY 添加到我們的首創創新藥物組合中，該藥物已在日本獲得批准，並於本月初在美國獲得批准。停經後骨質疏鬆症仍然是一種診斷不足和治療不足的疾病，骨折可能造成毀滅性後果，其中許多骨折是可以預測和預防的。我們很高興能夠走在創新產品的前沿，為全球數百萬可能從中受益的女性提供這些產品。

I want to take a moment to highlight our biosimilars business, which, we think, represents a compelling opportunity to leverage our world-class biologics capabilities. This business is now annualizing at more than $200 million this year with KANJINTI and AMGEVITA off to strong starts in Europe and select other international markets. We expect other launches this year, and we see biosimilars making important contributions to our revenue profile moving forward, especially as pressure on drug pricing creates increased demand for lower cost treatment options. Murdo will discuss our full product portfolio in some detail shortly.

我想藉此機會重點介紹一下我們的生物相似藥業務，我們認為，這代表著一個利用我們世界一流的生物製劑能力的絕佳機會。今年，隨著 KANJINTI 和 AMGEVITA 在歐洲和其他一些國際市場取得強勁開局，該業務的年化收入已超過 2 億美元。我們預計今年還會推出其他產品，我們認為生物相似藥將在未來為我們的收入做出重要貢獻，尤其是在藥品定價壓力導致對低成本治療方案的需求增加的情況下。Murdo 稍後將詳細介紹我們的全部產品組合。

Looking to the future, we are rapidly advancing a robust pipeline of innovative medicines, many of which have the potential to be first-in-class or best-in-class therapies. In oncology alone, we're capitalizing on our industry-leading BiTE portfolio and targeted therapies across a number of important disease areas, including multiple myeloma, AML as well as various solid tumors. As you know, oncology programs can move very rapidly from proof-of-concept to registration and we're excited about what we're seeing. You'll hear more from Dave Reese on our pipeline in a moment.

展望未來，我們正在快速推動一系列創新藥物的研發，其中許多藥物有可能成為同類首創或同類最佳療法。僅在腫瘤學領域，我們就充分利用了我們行業領先的BiTE產品組合和針對多種重要疾病領域的標靶療法，包括多發性骨髓瘤、急性髓系白血病以及各種實體瘤。如您所知，腫瘤治療計畫從概念驗證到註冊審批的進展速度非常快，我們對目前所看到的進展感到興奮。稍後您將聽到戴夫·里斯 (Dave Reese) 就我們的管道項目發表更多評論。

Our strong balance sheet and cash flow has enabled us to provide significant returns to our shareholders through buybacks and dividends, even as we invest in long-term volume-driven growth opportunities around the world. Our financial strength also gives us the ability to consider a wide range of business development opportunities consistent with our areas of strategic focus, while remaining disciplined to ensure we earn a solid return for shareholders.

我們強勁的資產負債表和現金流使我們能夠透過股票回購和分紅為股東帶來豐厚的回報，同時我們也在全球範圍內投資於以銷售為導向的長期成長機會。我們的財務實力也使我們能夠考慮符合我們策略重點領域的各種業務發展機會，同時保持自律，以確保為股東獲得穩健的回報。

Let me just say a few words also about health care reform in drug pricing. Simply stated, we're in favor of policies that provide more patients with greater access to better health care. And we continue to work with the administration and Congress to advance policies that harness the competitive power of the marketplace, encourage innovation and improve access to new therapies for patients. For example, we're supportive of the administration's proposal to move from back-end rebates to upfront discounts in order to lower out-of-pocket costs for patients. Even in the face of net price declines, as we experienced last year, patients are not seeing the benefits of rebates. In fact, out-of-pocket costs for patients have been rising in recent years, which underscores the need for the administration to move forward with its final rule.

我也想就藥品定價方面的醫療改革談幾句。簡而言之，我們支持能夠讓更多患者更容易獲得更好醫療保健的政策。我們將繼續與政府和國會合作，推動各項政策，以發揮市場的競爭優勢，鼓勵創新，並改善患者獲得新療法的機會。例如，我們支持政府提出的從後端回扣轉向前期折扣的提議，以降低患者的自付費用。即使像去年淨價下降，患者也看不到折扣帶來的好處。事實上，近年來患者的自付費用一直在上升，凸顯了政府推動最終規定的必要性。

Let me just close with one final message, which is that we will build on our recent transformation successes, and have the resources and determination to take advantage of the many opportunities in front of us to meet our competitive challenges and to deliver long-term growth.

最後，我想傳達一個訊息：我們將鞏固近期轉型取得的成功，並擁有足夠的資源和決心，抓住擺在我們面前的眾多機遇，應對競爭挑戰，實現長期成長。

Now let me invite David to share his remarks in the first quarter.

現在，我邀請大衛分享他在第一季的演講。

Okay. Thanks, Bob. The first quarter marked another period of solid performance for the company as we delivered mid-single digit volume growth globally, while we increased investment in the business and delivered year-over-year non-GAAP EPS growth in the first quarter.

好的。謝謝你，鮑伯。第一季標誌著公司又一個穩健的業績時期，我們在全球範圍內實現了中等個位數的銷量增長，同時增加了對業務的投資，並在第一季度實現了同比增長的非GAAP每股收益。

Turning to the financial results on Page 6 of the slide deck. Worldwide revenues were $5.6 billion in the first quarter with worldwide product sales of $5.3 billion declining 1% year-over-year as strong unit demand for our newer products was offset by declines in our mature products, including small molecule generic competition against Sensipar. Other revenues at $271 million increased $60 million, driven by royalty income growth.

接下來請看投影片第6頁的財務表現。第一季全球營收為 56 億美元，全球產品銷售額為 53 億美元，年減 1%，因為新產品的強勁需求被成熟產品的下滑所抵消，其中包括 Sensipar 面臨的小分子仿製藥競爭。其他收入為 2.71 億美元，比上年增長 6,000 萬美元，主要得益於特許權使用費收入的成長。

As we continue to make incremental investments to rapidly advance our innovative pipeline and maximize the value of our marketed products, our non-GAAP operating expenses increased 11% year-over-year. This also contributed to our non-GAAP operating income result at 9% lower than previous year.

隨著我們不斷增加投資，以快速推進創新產品線並最大限度地提高已上市產品的價值，我們的非GAAP營運費用年增了11%。這也導致我們的非GAAP營業收入比前一年下降了9%。

On a non-GAAP basis, cost of sales as a percent of product sales increased by 2 points to 14.7%, driven by higher manufacturing costs and product mix, partially offset by lower royalty expense. As mentioned last quarter, for the full year, we continue to expect year-over-year cost of sales expense to be flat to up depending on sales volume.

以非GAAP準則計算，銷售成本佔產品銷售額的百分比上升了2個百分點，達到14.7%，主要原因是製造成本和產品組合的增加，部分被較低的特許權使用費所抵銷。正如上個季度所提到的，我們預計全年銷售成本將與上一年持平或上升，具體取決於銷售量。

First quarter research and development expenses of $859 million were 16% higher due to increased investments in support of our multiple differentiated early-stage oncology programs. Research and development expense as a percent of product sales was 16.3% for the quarter. For the full year, we currently expect R&D spend on an absolute basis to rise in single-digit percentage terms in 2019. SG&A expenses increased 5% on a year-over-year basis, primarily driven by support for our newly launched products, including Aimovig, EVENITY and our biosimilar, AMGEVITA and KANJINTI.

由於增加了對多個差異化早期腫瘤計畫的投入，第一季研發支出為 8.59 億美元，比上一季成長了 16%。本季研發費用佔產品銷售額的16.3%。我們目前預計，2019 年全年研發支出絕對值將以個位數百分比成長。銷售、一般及行政費用年增 5%，主要原因是對我們新推出的產品（包括 Aimovig、EVENITY 和我們的生物相似藥 AMGEVITA 和 KANJINTI）的支援。

For the full year, we continue to expect SG&A spend to decline as launch expenses normalize and we continue with our resource allocation discipline. We remain on track to meet our initial 2019 operating expense guidance of in line versus 2018 on an absolute basis. Our operating expense guidance anticipates several important factors, including: One, that we continue to benefit from our productivity program; two, that we make appropriate investments in support of our in-line portfolio; three, that we advance our innovative and biosimilar programs; and four, that we continue to increase our global presence where we are experiencing rapid volume growth.

預計全年銷售、管理及行政費用將隨著產品上市費用的正常化以及我們繼續堅持資源分配原則而下降。我們仍有望實現 2019 年營運費用的初步預期，即絕對值與 2018 年持平。我們的營運費用預期考慮了幾個重要因素，包括：第一，我們繼續受益於我們的生產力提升計劃；第二，我們進行適當的投資以支持我們的現有產品組合；第三，我們推進我們的創新藥和生物類似藥項目；第四，我們繼續擴大我們在全球快速增長地區的業務。

Other income and expenses were a net $158 million expense in Q1. This is favorable by $24 million on a year-over-year basis. The non-GAAP tax rate was 14.6% for the quarter, an increase of 0.9 percentage points, primarily due to prior year tax benefit associated with intercompany sales under U.S. corporate tax reform. Non-GAAP net income declined 10% and non-GAAP earnings per share increased 3% year-over-year for the first quarter to $3.56 per share.

第一季其他收入和支出淨額為 1.58 億美元。與上年同期相比，這節省了 2,400 萬美元。本季非GAAP稅率為14.6%，上升了0.9個百分點，主要是由於美國企業稅制改革下與公司間銷售相關的上一年稅收優惠。第一季非GAAP淨利年減10%，非GAAP每股盈餘較去年同期成長3%至每股3.56美元。

Turning next to cash flow and the balance sheet on Page 7. Free cash flow was $1.7 billion. This was lower than first quarter last year, driven by lower net income and an increase in sales deductions paid to customers following higher third and fourth quarter 2018 sales. I note that Q2 will be negatively impacted as we make onetime tax payments of approximately $1 billion, including our second annual repatriation tax payment. We continue to provide significant cash returns to shareholders consistent with our commitments as we deployed $3 billion in Q1 to repurchase 15.9 million shares at an average price of $191 per share. Given our attractive share price, we plan to repurchase an incremental $1.5 billion to $2 billion of our shares in Q2.

接下來請看第 7 頁的現金流量表和資產負債表。自由現金流為 17 億美元。由於淨收入下降以及 2018 年第三季和第四季銷售額成長後支付給客戶的銷售扣款增加，該季度業績低於去年第一季。我注意到，由於我們要一次支付約 10 億美元的稅款，包括我們的第二筆年度匯回稅款，第二季將受到負面影響。我們持續履行承諾，為股東提供豐厚的現金回報。第一季度，我們投入 30 億美元，以每股 191 美元的平均價格回購了 1,590 萬股股票。鑑於我們股價具有吸引力，我們計劃在第二季額外回購價值 15 億至 20 億美元的股票。

Additionally, our first quarter dividend increased to $1.45 per share, an increase of 10% over last year. Cash and investments totaled $26.3 billion, a decrease of approximately $5.9 billion from the first quarter of last year. Our debt balance stands at $33 billion as of March 31st, carrying a weighted average interest rate of 4% at an average maturity of 10.8 years.

此外，我們第一季的股息增加到每股 1.45 美元，比去年增長了 10%。現金及投資總額為 263 億美元，比去年第一季減少了約 59 億美元。截至 3 月 31 日，我們的債務餘額為 330 億美元，加權平均利率為 4%，平均期限為 10.8 年。

Turning to the outlook for the business for 2019 on Page 8. We remain on track with our plans to continue to invest to advance our pipeline, including our early oncology programs, build out our global presence and drive long-term volume growth. In light of our Q1 performance, we are raising our 2019 guidance. Our revised revenue guidance is $22.0 billion to $22.9 billion versus previous guidance of $21.8 billion to $22.9 billion. This continues to reflect a range of outcomes related to Sensipar generic competition as well as the evolving competitive dynamics associated with the rest of our in-line portfolio.

接下來請看第 8 頁關於 2019 年業務展望的內容。我們將繼續按計劃投資，推動我們的研發管線，包括我們的早期腫瘤項目，拓展我們的全球業務，並推動長期銷售成長。鑑於我們第一季的業績表現，我們上調了2019年的業績預期。我們修訂後的營收預期為 220 億美元至 229 億美元，而先前的預期為 218 億美元至 229 億美元。這繼續反映了與 Sensipar 仿製藥競爭相關的各種結果，以及與我們其他在售產品組合相關的不斷變化的競爭動態。

With regard to our non-GAAP earnings per share guidance, we are revising the outlook to $13.25 to $14.30 per share versus previous guidance of $13.10 to $14.30 per share. Further, we are maintaining our non-GAAP tax rate guidance of 14% to 15%, and we continue to expect capital expenditures of approximately $700 million this year.

關於我們的非GAAP每股盈餘預期，我們將預期從先前的每股13.10美元至14.30美元調整為每股13.25美元至14.30美元。此外，我們維持非GAAP稅率預期在14%至15%之間，並繼續預期今年的資本支出約為7億美元。

This concludes the financial update. I will now turn the call over to Murdo.

財務更新到此結束。現在我將把電話轉給默多。

Thanks, David, and good afternoon, everyone. You'll find product sales information starting on Slides 10 and 11. We're off to a solid start in 2019 with continued volume-driven growth across our portfolio of newer products, while we successfully execute life cycle management strategies in our more mature brands.

謝謝你，大衛，大家下午好。產品銷售資訊從第 10 頁和第 11 頁開始。2019 年，我們取得了穩健的開局，新產品組合持續實現銷售成長，同時，我們也成功地在成熟品牌中實施了生命週期管理策略。

Moving to first quarter results, let me start with Repatha on Slide 12. Given the dynamic nature of the PCSK9 class and our confidence in Repatha, I want to provide some detail on its performance and growth prospects. Q1 sales grew by 15% year-over-year as we hold leading share of the PCSK9 class. Worldwide unit growth was 81% year-over-year with 90% unit growth in the U.S. The growth is attributable to increasing prescribing depth by cardiologists, increasing prescribing breadth by primary care physicians and increasing patient fulfillment following the introduction of lower list price Repatha.

接下來來看第一季業績，讓我先從第 12 張投影片上的 Repatha 開始。鑑於 PCSK9 類藥物的動態特性以及我們對 Repatha 的信心，我想詳細介紹它的性能和成長前景。第一季銷售額年增 15%，我們在 PCSK9 類藥物市場佔有領先份額。全球銷量較去年同期成長 81%，美國銷量較去年同期成長 90%。成長主要歸功於心臟科醫生處方深度增加、初級保健醫生處方範圍擴大以及 Repatha 定價降低後患者滿意度提高。

In Medicare, lower list price Repatha is now available for more than 60% of seniors. The next step is to make the lower list price version available to a majority of Part D patients at a lower fixed co-pay versus the current coinsurance structure. While this is underway, it's expected to improve early next year as Part D plans update for 2020. Currently, only 6% of Medicare patients are at a low fixed co-pay level of above $50. For patients covered by commercial insurance, approval rates have improved by 11 points year-over-year as we continue to secure improved payer utilization management criteria through contracting. We'll continue to work with health plans, PBMs and the U.S. administration to get lower list price Repatha to patients more rapidly, and we remain committed to discontinue our original list price Repatha once we see sufficient coverage in the market, which could be between now and the beginning of 2020. With regard to pricing, the blended net price for Repatha in the U.S. declined in Q1 due to annual contracts that took effect in January. We're optimistic that we will see a positive impact on volume growth and reported net sales over the longer term. Outside of the U.S., we continue to work with country authorities to optimize access and are pleased with our first-ever launch in China. Overall, our priority remains to help the large underserved population of high-risk cardiovascular patients that can benefit from Repatha.

在聯邦醫療保險（Medicare）中，超過 60% 的老年人現在可以以較低的價格購買 Repatha。下一步是讓大多數 D 部分患者能夠以較低的固定自付額獲得價格較低的版本，而不是採用目前的共同保險結構。雖然這項工作正在進行中，但隨著2020年D部分計畫的更新，預計明年年初情況會有所改善。目前，只有 6% 的聯邦醫療保險患者享有 50 美元以上的低固定自付額。對於享有商業保險的患者，隨著我們透過合約不斷確保支付方使用管理標準的改進，審批率比去年同期提高了 11 個百分點。我們將繼續與健康計劃、藥品福利管理機構和美國政府合作，更快地將價格更低的瑞百安（Repatha）提供給患者，並且我們仍然致力於在市場上獲得足夠的覆蓋後停止原價瑞百安（Repatha）的銷售，這可能在現在到 2020 年初之間。就定價而言，由於 1 月生效的年度合同，Repatha 在美國的混合淨價在第一季有所下降。我們樂觀地認為，從長遠來看，這將對銷售成長和報告淨銷售額產生積極影響。在美國以外，我們繼續與各國​​政府合作，優化市場准入，並對我們在中國的首次產品發布感到滿意。總的來說，我們的首要任務仍然是幫助大量未充分服務的、高風險心血管疾病患者群體，他們可以從 Repatha 中受益。

Now on to Prolia, on Slide 13. Prolia delivered another strong quarter with sales increasing 20% year-over-year, driven by 17% volume growth. As a reminder, given at 6-month dosing interval, Prolia exhibits a seasonal sales pattern with Q1 and Q3 representing lower sales than Q2 and Q4. Overall, market penetration of the addressable patient population is only in the mid-20% range, indicating significant potential for improved diagnosis and treatment. With this unique profile and through increasing investment, we expect Prolia will remain a very consistent growth driver.

接下來是 Prolia，請看第 13 張投影片。Prolia 又迎來了一個強勁的季度，銷售額年增 20%，其中銷量成長 17%。提醒大家，Prolia 的給藥間隔為 6 個月，其銷售呈現季節性模式，第一季和第三季的銷售額低於第二季和第四季。總體而言，目標患者群體的市場滲透率僅為 20% 左右，這表明在診斷和治療方面有很大的改善空間。憑藉這一獨特的優勢和不斷增加的投資，我們預計 Prolia 將繼續保持穩定的成長動能。

I'd like to take the opportunity to comment on a recent approval and launches of EVENITY in the U.S. and Japan, in conjunction with our partners UCB and Astellas. The World Health Organization calls osteoporosis a global epidemic, as there are fewer diagnosed and treated patients in the U.S. than a decade ago. In the U.S. alone, osteoporosis is responsible for 2 million fractures. And given the aging population, annual direct costs of osteoporosis are expected to reach $25 billion by the year 2025.

我想藉此機會談談我們與合作夥伴 UCB 和 Astellas 共同在美國和日本獲得 EVENITY 批准並上市的情況。世界衛生組織稱骨質疏鬆症是一種全球性流行病，因為與十年前相比，美國確診和接受治療的患者人數減少。光是在美國，骨質疏鬆症就導致200萬例骨折。鑑於人口老化，預計到 2025 年，骨質疏鬆症的年度直接成本將達到 250 億美元。

EVENITY has convenient once-monthly physician administered dosing for 12 months and strengthens Amgen's leading position in bone health with 2 highly innovative molecules that are complementary. We are confident in our ability to continue to penetrate this market. Our U.S. sales force is trained and is already promoting the product. Meanwhile, our launch in Japan through our joint venture with Astellas is off to a strong start.

EVENITY 每月只需醫生給藥一次，療程為 12 個月，方便快速。它由兩種高度創新且互補的分子組成，鞏固了安進在骨骼健康領域的領先地位。我們有信心繼續打入這個市場。我們的美國銷售團隊已經接受過培訓，並已開始推廣該產品。同時，我們與安斯泰來製藥的合資企業在日本的業務也取得了強勁的開局。

Now on to Aimovig on Slide 14. To begin, the unmet need for migraine is substantial. There are approximately 4 million individuals in the U.S. alone who take preventative medications for migraines. However, compliance is low as 75% discontinue therapy after only a year. Approximately 200,000 new patients in the U.S. have now tried Aimovig since it launched less than a year ago, and there remains a significant opportunity for growth as CGRP penetration of the overall market is low. We expect this number to expand considerably, given the 26% sequential TRx market growth for CGRP inhibitors in Q1. Prescriber breadth is consistently increasing as over 22,000 physicians have now prescribed Aimovig since launch. We're particularly encouraged that primary care adoption is steadily rising with nearly 8,000 prescribers to date. We also have indicators that our recently launched direct-to-consumer program is increasing patient awareness for Aimovig.

接下來請看第 14 張投影片，內容是 Aimovig。首先，偏頭痛患者未被滿足的需求非常巨大。光在美國就有約 400 萬人服用預防偏頭痛的藥物。然而，依從性很低，75% 的患者在一年後就停止了治療。自 Aimovig 上市不到一年，美國已有約 20 萬名新患者嘗試過該產品，由於 CGRP 在整體市場的滲透率較低，因此仍有很大的成長機會。鑑於 CGRP 抑制劑在第一季 TRx 市場連續成長 26%，我們預計這一數字將大幅成長。自上市以來，已有超過 22,000 名醫生開立了 Aimovig 處方，處方醫生的範圍正在擴大。我們尤其感到鼓舞的是，初級保健的普及率正在穩步上升，迄今為止已有近 8,000 名醫生開立了處方。我們也有跡象表明，我們最近推出的直接面向消費者的計劃正在提高患者對 Aimovig 的認識。

Now let me take a few minutes to help you understand Aimovig's performance in Q1. First, Amgen is the market leader with 40% share of new-to-brand prescriptions and 60% share of the total prescriptions exiting Q1. Aimovig benefits from strong market access conditions with over 75% approval rates for new patients in both commercial and Medicare Part D plans. Regarding net selling prices, we experienced a decline that is the net result of 2 dynamics. Recall that during the early launch phase of the product, a majority of paid prescriptions were reimbursed at near list price. Currently, the proportion of our business under commercial contract and receiving discounts is near 70%. Meanwhile, the proportion of paid versus free prescriptions increased to 60% at the end of the first quarter. Looking forward, we expect to see strong CGRP market growth, while competing effectively for share.

現在讓我花幾分鐘時間幫助您了解Aimovig在第一季的表現。首先，安進是市場領導者，在第一季末的新品牌處方中佔 40% 的份額，在所有處方中佔 60% 的份額。Aimovig 受益於良好的市場准入條件，在商業保險和聯邦醫療保險 D 部分計劃中，新患者的批准率均超過 75%。關於淨售價，我們經歷了下降，這是兩個因素共同作用的結果。回想一下，在產品上市初期，大部分的付費處方都是以接近標價的價格報銷。目前，我們業務中享有商業合約和折扣的比例接近 70%。同時，第一季末，付費處方與免費處方的比例上升至 60%。展望未來，我們預期CGRP市場將強勁成長，同時在市場佔有率競爭中發揮重要作用。

Offsetting this, Aimovig patient persistence will continue to be dynamic, given competing free product offerings in the market. We expect net prices to stabilize in 2019 as a majority of coverage decisions have been made. Additionally, the proportion of free prescriptions should continue to decline over the remainder of 2019. We are confident in the potential for Aimovig to positively impact patient lives and the recent launch of the single 140-milligram autoinjector will further enhance the patient experience.

但同時，鑑於市場上有其他免費產品，Aimovig 的患者堅持使用情況仍將保持動態變化。我們預計2019年淨價將趨於穩定，因為大部分承保決定已經做出。此外，2019 年剩餘時間內，免費處方的比例應該會繼續下降。我們對 Aimovig 能夠對患者生活產生積極影響的潛力充滿信心，最近推出的單支 140 毫克自動注射器將進一步提升患者體驗。

Moving to our hematology and oncology business. The portfolio of XGEVA, KYPROLIS, Nplate, Vectibix, BLINCYTO and IMLYGIC collectively totaled $1.2 billion in the quarter growing 8% year-over-year. Looking at additional details for some of the larger brands within this portfolio, let's start with XGEVA on Slide 16. In Q1, XGEVA grew 6% year-over-year primarily from volume as we gradually see share increasing to just above 60% in the U.S. We recently received preferred status over zoledronic acid in castration-resistant prostate cancer in the recently revised NCCN guidelines, reinforcing XGEVA superiority in this indication.

接下來轉到我們的血液腫瘤業務。XGEVA、KYPROLIS、Nplate、Vectibix、BLINCYTO 和 IMLYGIC 的投資組合在本季總計達到 12 億美元，較去年同期成長 8%。接下來，讓我們來看看該投資組合中一些較大品牌的更多細節，首先來看第 16 頁的 XGEVA。第一季度，XGEVA 年增 6%，主要得益於銷售成長，我們在美國市佔率逐漸成長至略高於 60%。最近，在 NCCN 最新修訂的指南中，XGEVA 在去勢抵抗性前列腺癌方面優於唑來膦酸，進一步鞏固了 XGEVA 在該適應症中的優越性。

Moving to KYPROLIS, which grew 10% year-on-year, driven primarily by growth in key markets, including the U.S., which had 12% growth. Our team continues to emphasize KYPROLIS overall survival benefit, and we are pleased to see increased adoption of the once-weekly dose approaching close to 20% of share of KYPROLIS use in the U.S.

KYPROLIS 年成長 10%，主要得益於關鍵市場的成長，其中美國市場成長了 12%。我們的團隊繼續強調 KYPROLIS 的整體存活獲益，我們很高興看到每週一次的劑量方案在美國的使用率接近 KYPROLIS 的 20%。

On to Enbrel, sales increased 4% year-over-year of which 2% was nonrecurring, which included a positive 10 point impact from changes in accounting estimates, offset partially by 8 points from unfavorable inventory changes. During Q1, rheumatology market growth accelerated by 12% versus the 6% on average over the last 8 quarters. Share trends continued and we recognized a limited benefit from net selling price in the quarter, which we expect to persist for the full year. We continue to invest in Enbrel, including the ENBREL Mini with AutoTouch, a multiuse device, which continues to receive positive feedback from physicians and patients.

恩利（Enbrel）的銷售額同比增長 4%，其中 2% 為非經常性增長，包括會計估計變化帶來的 10 個百分點的積極影響，但部分被不利的庫存變化帶來的 8 個百分點的影響所抵消。第一季度，風濕病市場成長速度加快至 12%，而過去 8 個季度的平均成長率為 6%。股價走勢持續，本季淨售價帶來的收益有限，我們預期這種情況將持續全年。我們繼續投資恩利（Enbrel），包括具有 AutoTouch 功能的恩利迷你型（ENBREL Mini），這是一款多用途設備，並持續獲得醫生和患者的正面回饋。

Next to our filgrastim brands, starting on Slide 19. In Q1, Neulasta sales declined 12% year-on-year, which included a $98 million purchase from BARDA. We exited Q1 with approximately 90% share of the long-acting segment, with Onpro holding share at close to 60% of the segment. Insurance coverage of Neulasta also remained strong in the U.S. with close to 90% of commercial lives and 99% of Medicare lives covered. Currently, we are seeing increased competition in medium-size clinics and small non-340B hospitals and are prepared for additional U.S. entrants in 2019 should they receive approval. Outside of the U.S., Q1 year-over-year sales declined 12%. We now face 3 long-acting biosimilar competitors in a number of countries in Europe and expect additional entrants during 2019, which will likely accelerate the pace of decline. More broadly, we remain confident that our experience, established record of quality, dependable supply and innovative solutions, such as Onpro, will serve us well as we compete account by account.

接下來是我們的 filgrastim 品牌，從第 19 張投影片開始。第一季度，Neulasta 的銷售額年減了 12%，其中包括從 BARDA 收購的 9,800 萬美元。第一季末，我們在長效製劑市場佔有約 90% 的份額，其中 Onpro 在該市場佔有近 60% 的份額。Neulasta 在美國的保險覆蓋率也保持強勁，商業保險覆蓋率接近 90%，醫療保險覆蓋率達到 99%。目前，我們看到中型診所和小型非 340B 醫院的競爭日益激烈，如果其他美國企業獲得批准，我們已準備好迎接 2019 年的更多美國企業進入市場。除美國以外，第一季銷售額年減 12%。目前，我們在歐洲多個國家面臨 3 個長效生物相似藥競爭對手，預計 2019 年還會有更多競爭者，這可能會加速市場下滑的腳步。更廣泛地說，我們仍然相信，憑藉我們的經驗、良好的品質記錄、可靠的供應和創新的解決方案（例如 Onpro），我們將在逐個客戶競爭中取得良好成績。

Turning to Slide 20. NEUPOGEN sales were $73 million in Q1 '19. Sequentially, U.S. Q1 results benefited from $7 million of accounting adjustments and NEUPOGEN exited the first quarter with roughly 30% share of the short-acting segment. Since the introduction of NEUPOGEN biosimilars in the U.S., cost to the health care system for short-acting filgrastim have come down meaningfully.

翻到第20張投影片。2019 年第一季度，NEUPOGEN 的銷售額為 7,300 萬美元。從季度來看，美國第一季的業績受益於 700 萬美元的會計調整，NEUPOGEN 在第一季末佔據了短效藥市場約 30% 的份額。自從 NEUPOGEN 生物相似藥在美國上市以來，短效非格司亭的醫療保健系統成本已顯著下降。

Switching to nephrology, starting on Slide 21. Q1 EPOGEN sales declined 10% due to lower net selling price. The first quarter benefited from approximately $20 million of large end customer purchases. Given our contractual pricing commitments with DaVita, net price will continue to decline for EPOGEN in 2019.

接下來轉到腎臟病學部分，從第 21 張投影片開始。由於淨售價下降，EPOGEN 第一季銷售額下降了 10%。第一季受惠於約 2,000 萬美元的大額終端客戶採購。鑑於我們與 DaVita 簽訂的合約定價承諾，EPOGEN 的淨價將在 2019 年繼續下降。

Aranesp declined 9% year-over-year in Q1 driven by lower volume due to increased competition. We expect Aranesp's sales to continue to decline at a faster rate in 2019 versus 2018 with both long-acting and short-acting competition in the U.S.

由於競爭加劇導致銷售量下降，Aranesp 在第一季年減 9%。我們預計，由於美國市場存在長效和短效藥物的競爭，Aranesp 的銷售額在 2019 年將繼續以比 2018 年更快的速度下降。

Parsabiv continues to experience solid growth. Independent and midsize dialysis providers utilize Parsabiv for a majority of their calcimimetic patients, while FMC and DaVita are gradually increasing adoption.

Parsabiv 持續保持穩健成長。獨立和中型透析服務提供者大多使用 Parsabiv 治療其鈣敏感受體激動劑患者，而 FMC 和 DaVita 正在逐步增加其採用率。

Turning to Sensipar. As a result of some at-risk small molecule generic launches, you can see on Slide 24, that our U.S. Q1 sales of $135 million are significantly lower than recent quarters. Given the intrusion of these at-risk launches that have now occurred, we expect U.S. sales in Q2 to be lower than Q1. Going forward, performance will be dependent on the outcome of legal proceedings and the rates of consumption of generic inventory across periods.

改用Sensipar。由於一些風險較高的小分子仿製藥上市，如幻燈片 24 所示，我們第一季在美國的銷售額為 1.35 億美元，遠低於最近幾季。鑑於目前已經發生的這些高風險產品上市活動的影響，我們預計第二季美國銷售額將低於第一季。展望未來，業績將取決於法律訴訟的結果以及各時期通用庫存的消耗速度。

I'd like to close by highlighting the strong performance of our biosimilars, where uptake of our European launches for KANJINTI and AMGEVITA is progressing as we anticipated. We're planning for multiple new launches from this portfolio over the next few years and look forward to bringing the value of these assets to patients and the health care system.

最後，我想重點介紹我們生物相似藥的強勁表現，KANJINTI 和 AMGEVITA 在歐洲的上市進展正如我們預期的那樣順利。我們計劃在未來幾年內推出該產品組合中的多個新產品，並期待將這些資產的價值帶給患者和醫療保健系統。

In summary, I am pleased with the solid execution and dedication of our team as our portfolio evolves in 2019. We're successfully launching new products, driving volume growth and demonstrating the value of our mature brands. We're also now establishing a strong presence in the biosimilars market with customers who appreciate the high-quality of Amgen services and product supply. I'm confident that we are prepared to maximize the opportunities to bring Amgen's products to a greater number of patients.

總而言之，我對我們團隊在 2019 年產品組合發展過程中展現出的紮實執行力和敬業精神感到滿意。我們正在成功推出新產品，推動銷售成長，並展現我們成熟品牌的價值。我們現在也在生物相似藥市場建立了強大的影響力，客戶們非常欣賞安進的高品質服務和產品供應。我相信我們已經做好充分準備，最大限度地抓住機遇，將安進的產品帶給更多病患。

And let me turn it over to Dave Reese.

現在讓我把麥克風交給戴夫·里斯。

Thanks, Murdo, and good afternoon, everyone. We are off to a rapid and exciting start to 2019 in R&D with progress across our pipeline. I'll begin with our oncology portfolio. We continue to advance our BiTE platform with approximately a dozen molecules now in or close to the clinic. In hematologic malignancies, at ASCO, we will provide an update on the dose escalation trial of our first-generation BCMA BiTE molecule, AMG 420. We are now enrolling patients in a dose expansion study. We also expect some of the first clinical data from our new generation BiTE platform by the end of the year with AMG 701 and extended half-life BCMA BiTE molecule. Our enthusiasm is high for our BCMA BiTE molecules as well as our CD38 bispecific and MCL-1 programs as we pursue our commitment to develop therapies that can make a meaningful impact in the treatment of multiple myeloma.

謝謝你，默多，大家下午好。2019 年伊始，我們的研發工作就取得了快速而令人振奮的進展，我們所有產品線都取得了進展。我先從我們的腫瘤產品組合開始介紹。我們持續推動 BiTE 平台的發展，目前已有約十幾種分子進入或接近臨床試驗階段。在血液惡性腫瘤方面，我們將在 ASCO 會議上提供我們第一代 BCMA BiTE 分子 AMG 420 劑量遞增試驗的最新進展。我們目前正在招募患者參與劑量擴展研究。我們也預計到今年年底，我們將獲得新一代 BiTE 平台的首批臨床數據，包括 AMG 701 和半衰期延長的 BCMA BiTE 分子。我們對BCMA BiTE分子以及CD38雙特異性抗體和MCL-1計畫充滿熱情，因為我們致力於開發能夠對多發性骨髓瘤治療產生重大影響的療法。

Other presentations at ASCO will include the first-in-human dose escalation study of AMG 212, a BiTE molecule directed against prostate-specific membrane antigen, or PSMA, which is highly and specifically expressed in a majority of human prostate tumors. This clinical study was conducted by Bayer through a license they had with Micromet prior to our acquisition. We believe the data from this trial provides proof-of-concept for the target and bispecific T-cell engager approach in solid tumors. And we have introduced a new half-life extended BiTE molecule, AMG 160, into clinical testing for prostate cancer. AMG 160 is now progressing briskly through dose escalation.

ASCO 的其他報告將包括 AMG 212 的首次人體劑量遞增研究，AMG 212 是一種針對前列腺特異性膜抗原 (PSMA) 的 BiTE 分子，PSMA 在大多數人類前列腺腫瘤中高度特異性表達。這項臨床研究是由拜耳公司透過其在被我們收購之前與Micromet公司簽訂的授權協議進行的。我們相信，這項試驗的數據為標靶和雙特異性 T 細胞銜接器方法在實體腫瘤治療的應用提供了概念驗證。我們已將一種新型的半衰期延長的 BiTE 分子 AMG 160 引入前列腺癌的臨床試驗中。AMG 160 目前正快速推進劑量遞增試驗。

As with all of the targets for which we have both first-generation and half-life extended BiTE molecules in clinical development, we will preferentially advance the half-life extended molecule if we observe comparable safety and efficacy between the 2 formats.

對於我們所有同時擁有第一代和半衰期延長型 BiTE 分子進行臨床開發的靶點，如果觀察到兩種形式的安全性和有效性相當，我們將優先推進半衰期延長型分子。

One final note on our BiTE programs. Recently, we have seen intriguing early clinical evidence of potentially enhanced activity of a BiTE molecule, in this case BLINCYTO, when given in combination with a PD-1 inhibitor. We anticipate sharing a larger dataset within a year or so. There's substantial evidence that T-cell activation leads to of upregulation of the PD-1 access providing a rationale for this combination. Based on these biologic and clinical insights, we are incorporating early checkpoint inhibitors combinations into many of our BiTE programs and I'll have more to say on this as studies initiate and we accrue data.

關於我們的BiTE項目，最後還有一點要補充。最近，我們看到了一些有趣的早期臨床證據，顯示 BiTE 分子（在本例中為 BLINCYTO）與 PD-1 抑制劑聯合使用時，其活性可能會增強。我們預計將在一年左右的時間內分享更大的數據集。有大量證據表明，T 細胞活化會導致 PD-1 通道上調，這為這種聯合療法提供了理論基礎。基於這些生物學和臨床見解，我們將早期檢查點抑制劑組合納入我們的許多 BiTE 計畫中，隨著研究的開始和數據的積累，我將對此發表更多看法。

I'd like to turn now to program of great interest, our KRAS G12C program, AMG 510. By way of background, RAS mutations occur in about 25% of all human cancers and the specific KRAS G12C mutation occurs in about 14% of lung adenocarcinomas and most common form of non-small cell lung cancer, but also occurs in about 4% of the colon cancers, a couple of percent of pancreatic tumors and at low frequency in various other cancers. RAS has been a target of active exploration since it was identified as one of the first oncogene, but it remained undruggable due to lack of traditional small molecule binding pockets on the protein. The G12C mutation produces a very shallow groove, which allowed us through elegant medicinal chemistry to design an irreversible small molecule inhibitor that locks KRAS into its inactive state.

現在我想談談大家非常感興趣的項目，我們的 KRAS G12C 項目，AMG 510。作為背景訊息，RAS 突變發生在約 25% 的人類癌症中，而特定的 KRAS G12C 突變發生在約 14% 的肺腺癌和最常見的非小細胞肺癌中，但也發生在約 4% 的結腸癌中，幾個百分點的胰腺腫瘤中，並在其他各種癌症中低頻發生。自 RAS 被確定為最早的癌基因之一以來，它一直是積極探索的目標，但由於蛋白質上缺乏傳統的小分子結合口袋，因此它一直無法成藥。G12C 突變產生了一個非常淺的溝槽，這使我們能夠透過巧妙的藥物化學設計出一種不可逆的小分子抑制劑，將 KRAS 鎖定在其非活性狀態。

I've spoken in the past on how we are improving productivity and accelerating the time line for drug development here at Amgen, and AMG 510 is an excellent example. When we knew that we could generate an inhibitor to a key oncogene that has been undruggable for over 30 years, we accelerated preclinical development and advanced the program from discovery to first-in-human trials in well under a year. Our presentations at AACR demonstrated that we have a highly specific molecule with good drug-like characteristics that can be dosed orally once a day. We also showed in preclinical models that AMG 510 may act synergistically with other agents. A particular interest were the preclinical data that AMG 510 inflamed tumors in part by upregulating Class I in MHC expression and enhanced sensitivity to checkpoint inhibition. We look forward to the opportunity to share the initial data from our first-in-human dose escalation study in patients with solid tumors containing KRAS G12C mutations at the upcoming ASCO meeting in Chicago, where we will also be hosting an Investor event. There's been a lot of questions on the extent of the data that will be available. And what I would say here is that -- you should expect basic exposure data and the cumulative efficacy and safety data we've got to date. While we've been in the clinic for only about 8 months, we have completed dose escalation and are expanding enrollment at the target dose.

我之前曾談到安進公司是如何提高生產力並加快藥物研發進度的，AMG 510 就是一個很好的例子。當我們得知可以針對一個30多年來一直無法成藥的關鍵癌基因開發出抑制劑時，我們加快了臨床前開發，並在不到一年的時間內將該計畫從發現推進到首次人體試驗。我們在 AACR 上的報告表明，我們擁有一種具有良好藥物特性的高度特異性分子，可以每天口服一次。我們也透過臨床前模型證明，AMG 510 可能與其他藥物產生協同作用。特別值得關注的是臨床前數據，這些數據表明 AMG 510 透過上調 MHC I 類表達和增強對檢查點抑制的敏感性來部分促進腫瘤發炎。我們期待有機會在即將於芝加哥舉行的 ASCO 會議上分享我們首次在攜帶 KRAS G12C 突變的實體瘤患者中進行的人體劑量遞增研究的初步數據，屆時我們還將舉辦一場投資者活動。關於將提供多少數據，大家有很多疑問。我想說的是——你們應該期待我們目前掌握的基本暴露數據以及累積療效和安全性數據。雖然我們進入臨床階段只有大約 8 個月，但我們已經完成了劑量遞增，並且正在擴大目標劑量組的招募範圍。

Moving forward, we will also be exploring AMG 510 in combination with checkpoint inhibitors based on the preclinical work I have described in various targeted therapies. And we are currently moving ahead to include a combination with a PD-1 inhibitor in our expansion study. Based on the early clinical data and feedback from our investigators, we are very optimistic on the potential for AMG 510 to address unmet medical need, and look forward to seeing many of you at ASCO.

接下來，我們將根據我在各種標靶療法中描述的臨床前研究，探索 AMG 510 與檢查點抑制劑的聯合應用。目前，我們正在推進將 PD-1 抑制劑納入我們的擴展研究。根據早期臨床數據和研究人員的回饋，我們對 AMG 510 解決未滿足的醫療需求的潛力非常樂觀，並期待在 ASCO 上見到你們中的許多人。

Finally, on oncology, we recently began recruiting patients in a combination study of venetoclax plus AMG 176, our intravenous MCL-1 inhibitor in non-Hodgkin's lymphoma and AML after seeing strong preclinical evidence of synergy. We're also rapidly advancing our oral MCL-1 inhibitor, AMG 397, through dose escalation in patients with hematologic malignancies. We expect initial clinical data from these programs later this year along with several other programs. In our accompanying presentation, you can find an overview of our hematology/oncology clinical portfolio.

最後，在腫瘤學方面，我們最近開始招募患者參與一項聯合研究，該研究將維奈托克與我們的靜脈注射 MCL-1 抑製劑 AMG 176 聯合用於治療非霍奇金淋巴瘤和急性髓系白血病，此前我們看到了強有力的臨床前協同作用證據。我們也正在快速推進口服 MCL-1 抑制劑 AMG 397 的研發，透過在血液惡性腫瘤患者中進行劑量遞增試驗來實現。我們預計將於今年稍後獲得這些項目以及其他幾個項目的初步臨床數據。在我們的配套簡報中，您可以找到我們血液腫瘤臨床產品組合的概述。

Moving to our other therapeutic areas. As a leader in bone health, we are pleased to receive approval of EVENITY, as Murdo noted, in the U.S. for the treatment of osteoporosis in postmenopausal women at high risk for fracture based on their disease characteristics or history of fracture. Postmenopausal osteoporosis, a silent epidemic that affects women in societies around the world, leads to approximately 2 million fragility fractures per year in United States alone. Despite this, it remains an underdiagnosed and undertreated disease with only 20% of these women receiving any type of osteoporosis treatment post fracture. EVENITY is the first and only anabolic therapy with a unique dual effect that both increases bone formation and to a lesser extent reduces bone resorption. The patients who need to rapidly increase bone mineral density in 12 months, EVENITY can reduce the risk of a first or subsequent fracture and in particular clinical fractures with symptomatic breaks that often lead to disability.

接下來，我們來看看其他治療領域。作為骨骼健康領域的領導者，我們很高興 EVENITY 獲得美國批准，正如 Murdo 所指出的那樣，用於治療停經後婦女的骨質疏鬆症，這些婦女根據其疾病特徵或骨折史判斷，骨折風險較高。停經後骨質疏鬆症是一種影響世界各地女性的隱形流行病，光是在美國每年就導致約 200 萬例脆性骨折。儘管如此，骨質疏鬆症仍然是一種診斷不足且治療不足的疾病，只有 20% 的骨質疏鬆症女性在骨折後接受任何類型的骨質疏鬆症治療。EVENITY 是首個也是唯一一個具有獨特雙重功效的合成代謝療法，既能增加骨形成，又能在一定程度上減少骨吸收。對於需要在 12 個月內快速增加骨礦物質密度的患者，EVENITY 可以降低首次或後續骨折的風險，特別是伴隨症狀性骨折的臨床骨折，這些骨折往往會導致殘疾。

In cardiovascular disease, we expect to complete enrollment of our omecamtiv mecarbil Phase III cardiovascular outcome study by mid-year, and recently passed an interim futility analysis with no recommended changes to the study. AMG 890, our Lp(a) siRNA also continues to progress, and we anticipate sharing data later this year or early next year. We recently received a pediatric indication for Corlanor for the treatment of stable symptomatic heart failure due to dilated cardiomyopathy in patients aged 6 months and older who are in sinus rhythm with an elevated heart rate.

在心血管疾病方面，我們預計將在年中完成 omecamtiv mecarbil III 期心血管結果研究的入組，並且最近通過了中期無效性分析，沒有建議對研究進行任何更改。我們的 Lp(a) siRNA AMG 890 也持續取得進展，我們預計今年稍晚或明年年初分享數據。我們最近收到了一份兒科適應症，Corlanor 可用於治療 6 個月及以上、竇性心律且心率升高的擴張型心肌病變引起的穩定症狀性心臟衰竭患者。

And finally, in migraine, as Murdo noted, we received approval for our single 140-milligram Aimovig autoinjector, our prefilled syringe in the U.S. For inflammation, we began enrolling a Phase II atopic dermatitis study with tezepelumab. I'm also pleased to report that our Phase III study for ABP 959, our biosimilar Soliris, is enrolling patients.

最後，正如 Murdo 所指出的那樣，在偏頭痛方面，我們的單支 140 毫克 Aimovig 自動注射器（預填充注射器）已在美國獲得批准。在發炎方面，我們開始招募患者參與 tezepelumab 治療異位性皮膚炎的 II 期研究。我很高興地報告，我們的生物相似藥 Soliris（ABP 959）的 III 期研究正在招募患者。

I'll close by thanking our staff for advancing our exciting pipeline and continuing to deliver for our patients. Bob?

最後，我要感謝我們的員工，感謝他們推動我們令人興奮的研發管線，並繼續為我們的患者提供優質服務。鮑伯？

Okay. Thank you. Let's open the line up now for questions, and perhaps I can ask our operator to remind you what the procedures are for submitting your questions. Thanks.

好的。謝謝。現在我們開放提問環節，或許我可以請我們的接線生提醒您提交問題的具體流程。謝謝。

(Operator Instructions) Our first question is from the line of Matthew Harrison from Morgan Stanley.

（操作員說明）我們的第一個問題來自摩根士丹利的馬修·哈里森。

Dave, I was hoping to ask a 2-part on KRAS. So I guess, the first thing is, it seems like you've progressed through the dose escalation period fairly rapidly. Is that because you hit the MTD faster than you were expecting or are there other factors, such as faster enrollment in play? And then how should we view the fact that you're pushing forward here with combinations with PD-1. Is part of that, the monotherapy efficacy that you've seen is below what you were expecting or you think you can drive efficacy substantially higher with those combinations?

Dave，我原本想問一個關於 KRAS 的兩部分問題。所以我想，首先，你似乎已經相當迅速地度過了劑量遞增期。這是因為你比預期更快達到了 MTD，還是有其他因素，例如更快的註冊參與率？那麼，我們該如何看待你在這裡推進與 PD-1 聯合用藥這一事實呢？部分原因是否在於，您觀察到的單藥治療療效低於預期，或者您認為透過合併用藥可以大幅提高療效？

Thanks, Matt, for the questions around the KRAS program. Let me take them in order. In terms of the dose escalation, I think, we'll present the clinical data at ASCO. We had a planned escalation -- dose escalation in the Phase I trial. We were able to move through that very quickly based on tolerability. We had quite brisk enrollment based on pre-identification of patients at most of our centers, and we're pleased to have been able to move along in 8 months in a population that is a fraction of lung cancers and other tumors. In terms of the combination, as I have indicated before, I think, based on the clinical setting, these molecules may find a home as either monotherapy or in combination. It's early days and we're moving quickly to investigate both of these approaches as we move forward. And the combinations will be not only with PDL-1 inhibitors based on some of the preclinical data that I described in terms of KRAS inhibitor inflaming tumors and upregulation MHC I expression, but also data we've generated on other components of the pathway. So I think, all of those will be pieces of what we explore going forward. This program is moving as quickly as almost any I have ever seen here at Amgen.

謝謝 Matt 提出關於 KRAS 程序的問題。讓我按順序來。關於劑量遞增的問題，我認為我們會在 ASCO 會議上公佈臨床數據。我們在 I 期試驗中計劃進行劑量遞增。基於耐受程度，我們能夠很快地克服這個問題。我們大多數中心都根據預先確定的患者招募情況迅速完成了招募工作，我們很高興能夠在 8 個月內在一個僅佔肺癌和其他腫瘤患者一小部分的群體中取得進展。至於聯合用藥，正如我之前所指出的，我認為，根據臨床情況，這些分子既可以作為單一療法，也可以作為聯合療法。現在還處於早期階段，我們將迅速推進，對這兩種方法進行研究。這些組合不僅包括基於我先前描述的KRAS抑制劑可抑制腫瘤發炎和上調MHC I表達的臨床前數據而與PDL-1抑制劑的組合，還包括我們針對該通路其他成分產生的數據。所以我認為，所有這些都將是我們未來探索的方向的一部分。這個專案的進度幾乎是我在安進公司見過的最快專案之一。

And our next question is from line of Terence Flynn from Goldman Sachs.

下一個問題來自高盛的 Terence Flynn。

Maybe Bob, would love your perspective just on the proposed Part B demonstration project? In particular, do you anticipate that the IPI proposal could remain here or do you expect there could be any changes?

鮑勃，或許我很想聽聽你對擬議的B部分示範計畫的看法？具體來說，您認為 IPI 的提案會保留下來，還是可能會有所改變？

Well, it's a proposed rule, as your question implies, Terence. And that enabled quite a bit of commentary and the administration has received something like 4,000 comments from different groups, including quite a wide range of physician groups and patient groups that were concerned about the proposal. It won't surprise you to know that we're concerned about it. We've expressed our concern as well. We're not interested in seeing patient access to innovative new medicines and physician choice impaired by a potential rule like this. So we and others in the innovative industry have expressed that to the administration. And I think if you compare the situation in United States where patients have access to innovative medicines very rapidly, in fact, if we just look at cancer, 95% of new cancer medicines are available to Medicare patients here in the U.S., and that compares to about 65% of the same medicines being available in France. And by the way, in France, they are available some 21 months later. So to a cancer patient, that can mean the difference between life and death. So we're not in favor of a rule like this that might have the effect of diminishing access to innovation and impairing investment in innovation over the long term. Having said that, we have been working with the administration around other proposals, that, we think, can help address the concerns of the administration and we'd like to continue to do that. So we think there are some things that the administration could pursue that would enable the government to get access to the market prices and still enable physicians and patients to use the medicines that they think are appropriate for these diseases.

正如你的問題所暗示的那樣，特倫斯，這只是一項擬議規則。這引發了大量的評論，政府收到了來自不同團體的約 4000 條評論，其中包括對該提案表示關注的眾多醫生團體和患者團體。你肯定不會驚訝地發現我們對此感到擔憂。我們也表達了我們的擔憂。我們不希望看到病人獲得創新藥物的機會和醫生的選擇權因這樣的潛在規則而受到損害。因此，我們和其他創新產業人士已經向政府表達了這項訴求。我認為，如果將美國的情況與法國的情況進行比較，就會發現美國的患者可以非常迅速地獲得創新藥物。事實上，如果我們只看癌症，95% 的新癌症藥物都可供美國聯邦醫療保險 (Medicare) 患者使用，而法國祇有大約 65% 的同類藥物可供使用。順便一提，在法國，它們大約21個月後才上市。所以對癌症患者來說，這可能意味著生死之別。因此，我們不贊成這樣的規則，因為它可能會減少創新機會，並從長遠來看損害對創新的投資。儘管如此，我們一直在與政府就其他提案進行合作，我們認為這些提案可以幫助解決政府的擔憂，我們希望繼續這樣做。因此，我們認為政府可以採取一些措施，使政府能夠獲得市場價格，同時仍能讓醫生和患者使用他們認為適合這些疾病的藥物。

And our next question from the line of Ying Huang from Bank of America Merrill Lynch.

接下來，我們向美國銀行美林證券的黃穎提問。

My first question had to do with the Neulasta trend. So year-over-year, sales came down by 12%, units went up by 1%, inventory went down 3%. So by my math, the net price is probably coming down by roughly 10%. Can you comment on the pricing trend for the rest of the year for Neulasta? And then can you quickly provide an update on the Enbrel panel ruling against Sandoz?

我的第一個問題與 Neulasta 的趨勢有關。因此，與去年同期相比，銷售額下降了 12%，銷量上升了 1%，庫存下降了 3%。根據我的計算，淨價可能會下降約 10%。您能否談談Neulasta今年剩餘時間的價格走勢？那麼，您能否簡要介紹一下恩利（Enbrel）專家小組對山德士（Sandoz）的裁決的最新進展？

So Ying, I'll take the first one and then I'll ask Bob perhaps to talk about the other question regarding Sandoz and Enbrel. I think overall we're pleased with how we're performing in the market despite 2 biosimilar competitors against Neulasta. In particular, we see good durability of our Onpro business, which is holding at around 60% share of the long-acting filgrastim franchise. We also continue to compete at an account by account level, and we defend, as you point out, significant volumes. What will drive further price erosion or potentially share erosion is the number of new competitive entrants and we're following that very closely going forward.

那麼，瑩，我先回答第一個問題，然後我可能會請鮑伯談談關於山德士和恩利（Enbrel）的另一個問題。儘管面臨兩款生物相似藥的競爭，但我認為我們總體上對Neulasta在市場上的表現感到滿意。尤其值得一提的是，我們的 Onpro 業務表現出良好的持久性，目前在長效非格司亭產品線中佔據約 60% 的市場份額。我們也繼續逐個客戶展開競爭，正如你所指出的那樣，我們捍衛著大量的市場份額。未來價格進一步下跌或市場份額可能進一步縮水的因素是新競爭者的進入數量，我們將密切關注這一趨勢。

On the court case, nothing new to report. As you know, we're waiting for the judge to rule and nothing new to report there.

關於這起訴訟案件，目前沒有什麼新的進展。如您所知，我們正在等待法官的裁決，目前還沒有新的進展可以報告。

And our next question is from the line of Geoffrey Porges from Leerink Partners.

下一個問題來自 Leerink Partners 的 Geoffrey Porges。

First question, David, just on the KRAS. Could you help us understand how -- in terms of expectations, how treatment response to this particular intervention should compared to other mutations in lung cancer that we're accustomed to seeing, for example, ALK or EGFR? Just is it likely to be as canonical, if you like, as those mutations? And then secondly, Murdo, could you just give us a little bit more color on Aimovig, in particular? It does focus though -- you've come out of some pressure in terms of share of new prescriptions. Is that a onetime event in the first quarter that we're seeing in the prescription data or has there been a step down because of a contract, and is this the new baseline?

大衛，第一個問題，就問KRAS而言。您能否幫助我們了解一下，就預期而言，這種特定乾預措施的治療反應與我們通常看到的肺癌突變（例如 ALK 或 EGFR）相比應該如何？它是否有可能像那些突變一樣具有代表性呢？其次，Murdo，您能否再詳細介紹Aimovig的情況？不過，它的確能起到聚焦作用——你在新處方份額方面已經擺脫了一些壓力。這是我們在第一季處方數據中看到的一次性事件，還是由於合約原因導致的下降，而這是否是新的基準線？

Sure. I'll go ahead and start with the question regarding KRAS biology. I think there is probably no specific answer for that, Jeff. In some tumors, this mutation will be a trunk mutation, a driver mutation and we may well expect monotherapy activity in other tumors based on the other suite of molecular alterations that are present, you may need combinations or another approach. I think these are all things we'll sort out. We'll be doing extensive molecular profiling on the tumors as we move forward to try to sort out the best predictors of response and resistance.

當然。我先從關於KRAS生物學的問題開始。傑夫，我覺得這個問題可能沒有確切的答案。在某些腫瘤中，這種突變將是主幹突變、驅動突變，我們可能會預期單藥治療對其他腫瘤有效，因為有其他一系列分子改變，您可能需要合併用藥或其他方法。我認為這些都是我們可以解決的問題。接下來，我們將對腫瘤進行廣泛的分子分析，以找出預測療效和抗藥性的最佳指標。

And Jeff, considering the huge unmet need in migraine, we continue to feel good about the opportunity to grow new prescription base and to continue to compete effectively for share. As you know, we're still the market leader with 60% TRx share, around 40% NBRx share. We have nice coverage across commercial and Medicare Part D payers. And we continue to drive good increases in the percent of patients that have -- that are paying for Aimovig, through commercial insurance benefit. So what we are seeing in our trends in our total prescriptions is some effect of the bolus of patients that we secured when we first launched into the market and working then through the free drug to paid transition. We're also trying to understand what the persistence is in the CGRP category. We saw that it was between 20% and 30% in clinical trials will be looking to see how that shapes up in the real world as we move forward.

傑夫，考慮到偏頭痛領域巨大的未滿足需求，我們仍然對拓展新處方基礎和繼續有效爭奪市場份額的機會感到樂觀。如您所知，我們仍然是市場領導者，擁有 60% 的交易份額和約 40% 的淨交易份額。我們在商業保險和聯邦醫療保險D部分支付方方面面都有良好的保障。我們持續推動透過商業保險福利支付 Aimovig 費用的患者比例穩定成長。因此，我們在處方總量趨勢中看到的是，我們最初進入市場時獲得的大量患者，以及隨後從免費藥物過渡到付費藥物所帶來的影響。我們也在嘗試了解 CGRP 類別中的持久性是什麼。我們在臨床試驗中發現，有效率在 20% 到 30% 之間，我們將密切關注它在現實世界中的表現。

And our next question is from the line of Kennen MacKay from RBC Capital Markets.

下一個問題來自加拿大皇家銀行資本市場的 Kennen MacKay。

A quick R&D question. You've mentioned tezepelumab Phase II moving forward in atopic derm. Hasn't tezepelumab missed a primary endpoint in the prior Phase IIa in AD? And what's sort of the difference in how you're thinking about this in AD or how has this evolved?

一個研發方面的問題。您提到 tezepelumab 在異位性皮膚炎的 II 期臨床試驗正在進行中。tezepelumab 在先前的 AD IIa 期臨床試驗中是否未達到主要終點？那麼，在AD中，你對這個問題的看法有何不同？或者說，這個問題是如何演變的？

I think we've gained a greater understanding of the approach to the disease, the variance in background medications. This is the disease that also has a waxing and waning natural history. And so we have, with our partners, designed a subsequent Phase II study, that, we think, will vigorously evaluate the utility of tezepelumab in AD.

我認為我們對這種疾病的治療方法以及背景藥物的差異有了更深入的了解。這種疾病的自然病程也呈現出時好時壞的趨勢。因此，我們與合作夥伴一起設計了一項後續的 II 期研究，我們認為該研究將有力地評估 tezepelumab 在 AD 中的應用價值。

And our next question is from line of Carter Gould from UBS Equities.

下一個問題來自瑞銀證券的卡特古爾德。

More of a change of pace for a second. Ask one on the omecamtiv progress you've been making. Specifically, if there are any additional planned interim analyses either for futility or stopping early for efficacy? And then just maybe your initial thoughts on how this -- you think this may be positioned in HF maybe alongside ENTRESTO?

稍微換個節奏。詢問一下你使用 omecamtiv 的進展。具體而言，是否有任何額外的計劃中期分析，無論是評估療效無效還是因療效而提前終止？那麼，您最初的想法是什麼？您認為它在對沖基金中的定位，或許可以和 ENTRESTO 一起？

Sure, this is Dave. I'll take that question. So typically, in these trials, there are interim analyses for efficacy. They are event-driven and we'll communicate at the appropriate time as we might expect those data. I think one of the things that excites us about omecamtiv is that its mechanism of action is novel. We think it's orthogonal to many of the existing therapies and should be able to be added to existing background therapies. To me, that's one of the potential great attractions of the drug for advanced heart failure.

當然，這是戴夫。我來回答這個問題。因此，在這些試驗中，通常會進行療效中期分析。它們由事件驅動，我們會在預期獲得這些數據時，在適當的時候進行溝通。我認為omecamtiv最讓我們興奮的地方之一是它的作用機制是全新的。我們認為它與許多現有療法正交，應該可以添加到現有的基礎療法中。對我來說，這是該藥物對晚期心臟衰竭患者俱有的巨大潛在吸引力之一。

And our next question is from the line of Yaron Werber from Cowen & Company.

我們的下一個問題來自 Cowen & Company 的 Yaron Werber。

So David, I've also a follow up on KRAS. Can you give us a little bit of sense, was this a typical 3 x 3 dose escalation or are you doing interpatient escalation? And would you breakout the results by tumor type as well? And then I have a quick question on Sensipar.

所以大衛，我還有關於 KRAS 的後續問題。能簡單說明一下嗎？這是典型的 3 x 3 劑量遞增方案，還是病人間劑量遞增方案？您能否也依腫瘤類型細分一下結果？然後我還有一個關於Sensipar的問題。

Yes, what I'll say is all those questions will be answered at ASCO. I don't want to get out in front of our investigators and steal their thunder. But we will provide great detail in the Phase I presentation.

是的，我可以說，所有這些問題都將在ASCO會議上得到解答。我不想搶在調查人員前面，搶了他們的風頭。但我們將在第一階段的報告中提供詳細資訊。

What was your second question, Yaron?

亞倫，你的第二個問題是什麼？

Sensipar. Wanted to ask a second question about Sensipar?

Sensipar。想再問一個關於Sensipar的問題嗎？

Can you hear me?

你聽得到我嗎？

Sorry. Go ahead, Yaron.

對不起。請繼續，亞倫。

Can you give us a sense or the launchers for Sensipar. Are they Zydus and Piramal? And are they still subject to the litigation coming up in June?

能為我們介紹一下Sensipar的上市計畫嗎？他們是 Zydus 和 Piramal 嗎？他們是否仍將受到六月即將開庭的訴訟的影響？

Yes, so what I'd say -- this is Meline. So first point is if you look at the guidance that we offered this afternoon, what we've given you is while it's a bit narrower, it's still quite broad, and the reason for that is the uncertainty around will we have additional launches this year or not. And of course, that is driven by the fact that we do have litigation that's still going on, and we expect that to conclude here sometime in the coming months. So hence, the breadth of the guidance.

是的，所以我想說的是——這是梅琳。首先，如果你看一下我們今天下午提供的指導意見，雖然範圍有所縮小，但仍然相當廣泛，原因是今年是否會有額外的發射存在不確定性。當然，這是因為我們目前還有訴訟正在進行中，我們預計訴訟將在未來幾個月內結束。因此，指導意見涵蓋範圍很廣。

And our next question is from the line of Do Kim from BMO Capital Markets.

下一個問題來自 BMO 資本市場的 Do Kim。

I wanted to ask about the Humira biosimilar market in Europe. We know that biosimilars in the European landscape is fairly mature. But with so many competitors out there, how are you seeing how the market for Humira will shape out, and how do you position your biosimilar with so many competitors?

我想了解歐洲的阿達木單抗生物相似藥市場狀況。我們知道，歐洲的生物相似藥市場已經相當成熟。但是，面對如此多的競爭對手，您如何看待 Humira 的市場格局？面對如此多的競爭對手，您又將如何定位您的生物相似藥？

Thank you, Do, for the questions. This is Murdo. What we're seeing in Europe, in general, in the biosimilars market is more rapid penetration of the biosimilars of the innovator compounds. So higher biosimilar penetration in general across a number of different categories. Our shares are more or less in line with what we had anticipated and price is a little lower. So we are seeing higher volume due to that penetration offsetting somewhat lower prices. And the prices you have to be a little bit careful. Most of the interest and news that we read about on pricing, particularly in the case of the Humira biosimilar, were related to tender prices in some smaller European markets. And those were pretty significant winner takes all price reductions. What you're seeing in the broader marketplace at the national formulary level and at regional formularies are better prices holding up quite well, and we foresee the biosimilar business to be a significant revenue driver for some time to come.

謝謝Do的提問。這是默多。總的來說，我們在歐洲生物相似藥市場看到的是，創新藥的生物相似藥滲透速度更快。因此，生物相似藥在許多不同類別中的滲透率總體較高。我們的股票表現基本上符合預期，價格略低於預期。因此，由於市場滲透率的提高，銷量有所增加，抵消了價格略微下降的影響。價格方面需要稍微注意一下。我們所了解到的關於定價的大部分信息和新聞，特別是關於阿達木單抗生物類似藥的定價信息，都與一些較小的歐洲市場的招標價格有關。而且這些都是力度相當大的贏家通吃的全額降價。在國家藥品目錄和地區藥品目錄等更廣泛的市場中，我們看到的是價格更加優惠且保持良好，我們預計生物相似藥業務將在未來一段時間內成為重要的收入驅動因素。

And our next question is from the line of Jay Olson from Oppenheimer.

我們的下一個問題來自奧本海默公司的傑伊·奧爾森。

Thanks for the warm welcome. I'm curious about the VESALIUS-CV outcomes trial for Repatha. Can you comment on the key differences between this outcomes trial and the FOURIER trial, and how that study may impact the long-term commercial potential for Repatha? And then separately, any thing we should be looking out for at AAN next week in terms of data for Aimovig?

謝謝大家的熱情歡迎。我對 Repatha 的 VESALIUS-CV 結果試驗很感興趣。您能否評論一下這項結果試驗與 FOURIER 試驗之間的主要區別，以及該研究可能會如何影響 Repatha 的長期商業潛力？另外，關於Aimovig的數據，下週在AAN大會上我們該關注哪些面向？

Dave, do you want to get both of those?

戴夫，你兩個都要嗎？

Yes, let me -- well, I'll get half of the Repatha question and then Murdo will take the other one, and I can address Aimovig at AAN. So in terms of VESALIUS, these are patients with known -- essentially known coronary artery disease, but who have not had an event. So they are very high risk. It's a population that numbers in the millions beyond what we were -- the target population studied in the FOURIER trial. We think it should add to the substantial body of evidence that we have with Repatha in another high risk population. Murdo, you may want to comment on the commercial component?

是的，讓我——好吧，我會回答 Repatha 問題的一半，然後 Murdo 會回答另一半，然後我可以在 AAN 上向 Aimovig 提問。因此，就 VESALIUS 而言，這些患者患有已知的——基本上是已知的冠狀動脈疾病，但尚未發生事件。所以他們的風險非常高。這是一個比我們——FOURIER 試驗中研究的目標群體——人數多出數百萬的群體。我們認為這應該能為我們在另一個高危險群中使用 Repatha 所獲得的充分證據錦上添花。Murdo，你或許想對商業部分發表一下看法？

Yes. We're continuing to work hard to penetrate that high-risk cardiovascular patient population and compete in that category. We are seeing the data are more similar than different to what we've already had in the public domain. And we're really pleased with the 80% -- 81% volume evolution, and we continue to believe that more and more physicians are understanding the value of treating these higher-risk cardiovascular patients.

是的。我們正持續努力打入高風險心血管疾病患者群體，並在該領域競爭。我們發現這些數據與我們已公開的數據相似之處多於不同之處。我們對 80% 至 81% 的病例量增長非常滿意，我們繼續相信越來越多的醫生正在認識到治療這些高風險心血管疾病患者的價值。

And then in terms of the Aimovig data at the American Academy of Neurology meeting, which is starting in 4 or 5 days, we do have what I think are some very interesting data, long-term safety and efficacy data in both chronic and episodic migraine. The abstracts for those who are interested are up now. In chronic migraine, for example, we were able to show that roughly 2/3 of patients were able to convert to episodic migraine, meaning fewer than 15 migraine days per month. And on average depending on the population and the dose, the number of migraine headache days per month was reduced by 8 to 12 days per month. That's a very substantial clinical impact for these patients as you can imagine. So those data are coming out within the next week or so.

至於 Aimovig 在美國神經病學會會議上的數據（該會議將在 4 或 5 天後開始），我們確實有一些我認為非常有趣的數據，包括慢性偏頭痛和發作性偏頭痛的長期安全性和有效性數據。有興趣的讀者可以查看摘要。例如，在慢性偏頭痛中，我們能夠證明大約 2/3 的患者能夠轉化為發作性偏頭痛，這意味著每月偏頭痛發作天數少於 15 天。平均而言，根據人群和劑量，每月偏頭痛天數減少了 8 至 12 天。您可以想像，這對這些患者來說是一個非常重大的臨床影響。所以這些數據將在接下來的一週左右公佈。

Those data also support the launch of the new single 140-milligram dose of Aimovig, given that patients who got to the higher dose tends to do even better on conversion.

這些數據也支持推出新的單次 140 毫克劑量的 Aimovig，因為服用較高劑量的患者在轉換劑量時往往效果更好。

Right. And there are, in those patients, complete responders, which is remarkable in this disease.

正確的。而且，在這些患者中，有完全緩解的患者，這在這種疾病中是相當了不起的。

And our next question is from the line of Michael Yee from Jefferies.

下一個問題來自傑富瑞集團的麥可葉。

I guess, I wanted to ask a question related to 2 ongoing litigation issues, some are with the same company. One is, if, for some reason, the IP does not go in your favor, for some reason, on Enbrel, what are the implications and what are the scenarios that we should know or for shareholders to know? And then maybe you can just comment on the separate litigation related to Aimovig? I think, it was a bit surprising to people, so maybe just comment on what the implications are there?

我想問一個與兩起正在進行的訴訟案件相關的問題，其中一些案件涉及同一家公司。一是，如果由於某種原因，Enbrel 的智慧財產權對您不利，那麼會產生哪些影響？我們或股東應該了解哪些情況？然後，您或許可以就與 Aimovig 相關的另一起訴訟發表一些評論？我覺得這有點出乎大家的意料，所以或許可以評論一下這其中的意思？

Yes, sure, Mike. I can understand that. On the first one, we feel pretty strongly about the IP case that was presented. And so obviously, if the judgment were to go against us, we would immediately appeal. But on the Aimovig partnership, look, the first thing to underscore is that the teams in the field are committed to doing what's right for patients here. And it's unfortunate that we have a dispute with our partner about this matter, but that's why we have a dispute resolution option specified in a contract like this. So we feel that our partner is enabling a competitor product, and so we want to pursue that matter in court and that's where we are. But as I said, that will probably play out over a period of time. And in the meanwhile, both teams are committed to continuing to pursue this therapy for those patients who benefit from it.

好的，當然可以，麥克。我能理解。對於第一個問題，我們對提出的智慧財產權案例感到非常認同。因此，很顯然，如果判決對我們不利，我們將立即提起上訴。但是關於 Aimovig 的合作關係，首先要強調的是，現場團隊致力於為患者做正確的事情。很遺憾我們與合作夥伴就此事存在爭議，但這就是為什麼我們在合約中規定了爭議解決選項的原因。因此，我們認為我們的合作夥伴正在支持競爭對手的產品，所以我們想透過法律途徑解決這個問題，這就是我們目前的情況。但正如我所說，這可能需要一段時間才能顯現出來。同時，兩支團隊都致力於繼續為那些能從中受益的患者探索這種療法。

And our next question is from the line of Alethia Young from Cantor Fitzgerald.

我們的下一個問題來自坎托·菲茨杰拉德的阿萊西亞·楊的詩句。

I just wanted to talk a little bit about the biosimilars there because I know you had put out kind of a longer term guidance of some sort around the $3 billion number. But I just wanted -- now that we have some biosimilars in the market, how do you guys are thinking about the prospects? Do you think it's a more attractive business, less attractive, about the same? Just wanted you to kind of frame some of the puts and takes that you think about essential longer term value of that business?

我只是想稍微談談生物相似藥的情況，因為我知道你們曾經發布過一個關於 30 億美元左右的長期指導意見。但我只是想問——既然現在市面上已經有一些生物類似藥，你們覺得前景如何？你認為這是一個更有魅力的生意、吸引力下降的生意，還是吸引力差不多？我只是想請您大致談談您認為對這家企業長期價值至關重要的幾個買入和賣出點是什麼？

Alethia, obviously, it's still very early days in the U.S. Based on our European experience, and what we continue to believe the market outlook is in the U.S. wouldn't change the long-range comments we've made historically. I think they still hold up and we continue to pursue a number of really interesting and solid molecules, and we continue to prepare for launches in the U.S. in the not-too-distant future.

Alethia，顯然，現在進入美國市場還處於非常早期的階段。根據我們在歐洲的經驗，以及我們持續認為的美國市場前景，我們不會改變我們過去所做的長期評論。我認為它們仍然有效，我們將繼續研究一些非常有趣且可靠的分子，並繼續為在不久的將來在美國推出這些分子做準備。

And our next question is from the line of Cory Kasimov from JPMorgan.

下一個問題來自摩根大通的科里·卡西莫夫。

Wanted to ask on Aimovig, and wondering if you could provide some color on the constipation issues that some docs and your competitors talk about with the drug. I guess, I am wondering how frequently this leads to discontinuations and what you might be doing to alleviate this assuming this is even, in fact, an issue?

我想問一下關於Aimovig的問題，想知道您能否就一些醫生和您的競爭對手提到的該藥物引起的便秘問題提供一些資訊。我想知道這種情況導致停產的頻率有多高，以及如果這確實是一個問題，你們可能會採取哪些措施來緩解這種情況？

Thanks for the question. We do hear about this issue, and obviously we're always making sure that we provide necessary patient support and physician support around the safety and efficacy of our product. But we also think on this one, there's quite a large amount of rhetoric that's has been created around this issue, given how the product performed in clinical trials and the stated incidence of constipation in our label, it will even be reported in the long-term follow-up data at AAN. So I think it's been well characterized in good, well designed open-label and continuous clinical trials. We're also pleased that many physicians, particularly the prescribers in the large-scale headache centers are telling us that it's a relatively low incidence and that they have very little trouble having patients started on Aimovig and persisting. I think some of the other things we're seeing in persistence, and I mentioned it in response to an earlier question, just as we -- given that we were in the entire market for many months without competition, we are seeing some persistence effects in our continuing patient population that are different than what you might have concluded from looking at the clinical trials. And that's a function of both people who are moving from one free trial offer to another and it's a function of people who are perhaps not pursuing commercial insurance, and obviously there's a small component of that, that is switch away to other agents. So there's still an evolving understanding of how persistent patients are, to your question, on discontinuation of Aimovig. So -- and it will take many months to understand that you need at least a 12-month look back period, that puts us in the 18- to 24-month time frame before we'll be able to actually ascertain durability.

謝謝你的提問。我們確實聽到了這個問題，而且顯然我們一直在確保為患者和醫生提供必要的支持，以確保我們產品的安全性和有效性。但我們也認為，鑑於該產品在臨床試驗中的表現以及我們在標籤中聲明的便秘發生率，圍繞這個問題已經產生了大量的言論，甚至在AAN的長期隨訪數據中也會報告這一點。所以我認為，在設計良好的開放標籤和持續的臨床試驗中，它已經得到了充分的表徵。我們也很欣慰地看到，許多醫生，特別是大型頭痛中心的處方醫生告訴我們，這種情況發生率相對較低，而且他們讓患者開始服用 Aimovig 並堅持服用幾乎沒有任何困難。我認為我們在患者持續性方面也看到了一些其他現象，我在回答先前的問題時也提到過，正如我們——鑑於我們在整個市場中連續幾個月沒有競爭對手，我們在持續的患者群體中看到了一些持續性效應，這與你從臨床試驗中得出的結論有所不同。這不僅與人們從一個免費試用優惠轉向另一個免費試用優惠有關，也與人們可能不打算購買商業保險有關，顯然，其中有一小部分人轉而選擇其他代理人。所以對於您提出的「病人對停用 Aimovig 的堅持程度」這個問題，我們仍然在不斷發展理解。所以——而且需要好幾個月的時間才能明白，至少需要 12 個月的回顧期，這意味著我們需要 18 到 24 個月的時間才能真正確定其耐用性。

And Cory, from a clinical perspective, I would reiterate what Murdo said. What we hear from physicians, experts is that they see it at a low incidence. It's clinically quite manageable. They don't really view it as any sort of barrier at all.

科里，從臨床角度來看，我同意默多的說法。我們從醫生和專家那裡了解到，他們認為這種情況發生率很低。臨床上很容易處理。他們根本不認為這是一種障礙。

And our next question is from the line of Geoffrey Meacham from Barclays.

下一個問題來自巴克萊銀行的傑弗裡·米查姆。

I just had a pipeline question for Dave, broadly on the earlier pipeline. You're still in dose escalation for BCMA, for PSMA, for KRAS, et cetera. But presumably, you've had some evidence of efficacy, and I know it's data-dependent, but is there a path to moving rapidly into pivotal studies, even if it's a registration phase to it? Just wasn't sure if this was even an option or if there have been discussion with regulators on this?

我剛才有個關於早期管道的問題想問戴夫。您目前仍在進行 BCMA、PSMA、KRAS 等標靶藥物的劑量遞增治療。但想必你們已經獲得了一些療效證據，我知道這取決於數據，但是否有辦法快速進入關鍵性研究階段，即使只是註冊階段？我只是不確定這是否是一個可行的方案，或者是否已經與監管機構討論過這個問題？

Yes, of course, that will vary program by program. But I would say in general is that our goal in these programs will be to move as quickly as we can through dose escalation and then move into expansion and potentially pivotal phases of the program. I think given the target diseases and the potential regulatory paths, that's a realistic expectation and that's how we've planned many of the clinical development programs.

當然，具體情況會因項目而異。但總的來說，我認為這些項目的目標是盡快完成劑量遞增階段，然後進入計畫的擴展階段和可能的關鍵階段。我認為，考慮到目標疾病和潛在的監管途徑，這是一個現實的預期，這也是我們規劃許多臨床開發項目的方式。

And our next question is from the line of Umer Raffat from Evercore ISI.

我們的下一個問題來自 Evercore ISI 的 Umer Raffat。

I wanted to go back to KRAS again for a quick second. And basically ask, based on everything you saw in the preclinical data, would you have expected to hit MTD by this third or fourth dose? And also you mentioned seeing cumulative efficacy at ASCO is what you intend to show. Should we be expecting a dose response? And then separately on Enbrel, was curious what the net price trend was in the first quarter year-over-year adjusting for the accounting treatment?

我想再快速地回到 KRAS。基本上，根據你在臨床前數據中看到的一切，你預期在第三劑或第四劑時就能達到最大耐受劑量嗎？而且您也提到，您打算在 ASCO 上展示累積療效。我們是否應該預期會出現劑量反應？另外，關於恩利（Enbrel），我想了解經會計處理調整後，第一季同比淨價趨勢如何？

Okay. I think there were several questions there.

好的。我認為那裡有好幾個問題。

In relation to KRAS, again, the clinical data, we'll present, so I won't comment on the specifics of dose response. I will say that this is an irreversible inhibitor and our anticipation is that achieving adequate exposure for a period of time, probably a few hours over the course of the dosing interval a day, is adequate to poison the target and inhibit signaling. And so our dose escalation was planned with that goal in mind. And we'll prevent -- present complete details in about a month at ASCO.

關於 KRAS，我們將展示臨床數據，因此我不會評論劑量反應的具體細節。我要說明的是，這是一種不可逆抑制劑，我們預計，在一天給藥間隔期間，達到足夠的暴露時間（可能為幾個小時）就足以毒害標靶並抑制訊號傳導。因此，我們的劑量遞增計畫就是以這個目標為導向的。我們將採取措施防止這種情況發生—將在大約一個月後的ASCO會議上公佈完整細節。

And Umer, on your question regarding Enbrel, we did have a strong quarter on Enbrel. It was primarily driven by a strong market across rheumatology. And we did see some net price benefit based on that price increase as well as improved contracts in the new year.

Umer，關於你問的Enbrel的問題，我們本季Enbrel的表現確實很強勁。這主要是由風濕病學領域的強勁市場需求所驅動的。我們確實從價格上漲以及新年合約的改善中看到了一些淨價格收益。

Okay. We have time for 1 or 2 questions, so we...

好的。我們只有時間回答一兩個問題，所以…

Yes, Ian. Let's -- since it's past 6 p.m. on the east cost, let's take 2 more questions.

是的，伊恩。既然已經過了下午6點，那就…關於東岸，我們再來回答兩個問題。

Our next question is from the line of Ronny Gal from Bernstein.

我們的下一個問題來自伯恩斯坦的 Ronny Gal 的系列。

Two, if I may. First, if you can break for us the relative sales of KANJINTI and AMGEVITA, just trying to keep track on those molecules individually? And second on Aimovig, Murdo, you've mentioned that you're expecting net price stabilization of this molecule. And I was kind of wondering about this comment. It seems like the payers have not really selected their preferred agency yet, even if I just added Teva back in, so I was wondering there wouldn't be another step down in pricing expected when they choose to prefer agents. And then with orals coming about a year out, wouldn't that cause another step down in pricing at that point. So I'm just -- can you put that comment in context?

如果可以的話，我想說兩個。首先，您能否為我們詳細列出 KANJINTI 和 AMGEVITA 的相對銷售情況，以便我們分別追蹤這些分子的銷售情況？其次，關於 Aimovig，Murdo，你提到你預期這種分子的淨價格會趨於穩定。我有點好奇這則評論是什麼意思。即使我重新添加了 Teva，付款方似乎還沒有真正選擇他們偏好的代理商，所以我想知道，當他們選擇偏好的代理商時，價格是否會進一步下降。而口試還有大約一年時間，那屆時價格豈不是會再次下降嗎？所以，我只是──你能解釋一下這句話的上下文嗎？

Thanks, Ronny. We're not breaking out the biosimilars sales by brand yet, still a volatile market. But we are happy with both trends on both products going forward. We're also -- as you look at Aimovig, my comment, if you'll recall, has 2 components to it; one is the net price reduction based on additional contracts that could occur throughout the course of the year plus a rising percentage of prescriptions that are paid, and the two offsetting one another leading to a stable price, at least for this year. And I think that would be my clarification to your question.

謝謝你，羅尼。我們目前還沒有按品牌細分生物相似藥的銷售額，因為市場仍然波動較大。但我們對這兩款產品未來的發展趨勢都感到滿意。我們——正如你看到的 Aimovig，如果你還記得的話，我的評論有兩個部分；一是基於全年可能達成的額外合同以及處方藥支付比例的上升而實現的淨價格降低，這兩者相互抵消，至少在今年內將價格穩定下來。我想這就是我對你問題的解答了。

Ian, let's take one last question, after which Bob will make some closing comments.

伊恩，我們再問最後一個問題，之後鮑伯將作總結發言。

And our last question is from the line of Salim Syed from Mizuho Securities.

最後一個問題來自瑞穗證券的 Salim Syed。

I guess, one for me, a multipart one, on Repatha, on the new CVOT trial. I guess, maybe if you could just give us some color on what the genesis of the design of that trial was, given it seems to mimic Medicines' companies align for almost like line for line. And should we be thinking of that as a validation of inclisiran's value proposition in the marketplace as we think about long-term Repatha sales?

我想，對我來說，有一篇是關於 Repatha 的，一篇是關於新的 CVOT 試驗的多部分文章。我想，如果您能給我們介紹一下該試驗的設計緣起，那就太好了，因為它似乎與製藥公司幾乎逐一進行的試驗如出一轍。我們是否應該將此視為 Inclisiran 在市場上的價值主張的驗證，尤其是在考慮 Repatha 的長期銷售情況時？

Yes, I'd be happy to address that question. I mean, that's -- we designed that study from a technical perspective just the way we design any study based on expected magnitude of effect, target population, all of the typical statistical calculations that go -- in clinical perspectives that go into study design. We weren't using anyone else's trial as a template for that study, and I wouldn't call it validation of anything, but the internally consistent results from that trial alone.

是的，我很樂意回答這個問題。我的意思是，我們從技術角度設計了這項研究，就像我們根據預期效果的大小、目標人群以及所有典型的統計計算來設計任何研究一樣——從臨床角度來看，這些計算都會納入研究設計中。我們沒有以其他任何人的試驗為模板進行這項研究，我也不會稱之為對任何事情的驗證，而僅僅是該試驗內部一致的結果。

Bob, would you like to make some closing comments?

鮑勃，你還有什麼要補充的嗎？

Okay. Thank you. Well, in closing, we're off to a good start in 2019, and I hope you share our team's enthusiasm for our long-term prospects. We have a number of medicines that are in-line portfolio that can and we expect will benefit significantly more patients as we grow longer term. We have an emerging portfolio of branded biosimilars, which we've talked about, and we think would be a new source of growth for us. We're advancing a record number of potential new medicines in our pipeline targeted at some of the most prevalent, costly and serious diseases facing society today. Our financial strength, I think, is evident, again, this quarter, and our durable cash flows will allow us to continue to invest in the business, but also provide meaningful returns to our shareholders and deliver transformational innovation for patients. Most importantly, I want to just end by thanking our staff who are fully engaged and behind our mission and thank them for the work they did to get us off to a solid start in 2019. We look forward to talking to all of you at the ASCO Investor meeting, and then at the second quarter call in July. Thank you.

好的。謝謝。最後，我們2019年開局良好，希望你們和我們團隊一樣對公司的長期前景充滿熱情。我們擁有一系列在研藥物，這些藥物能夠並且我們預計隨著公司長期發展，將會使更多患者受益。我們正在開發一系列新興的品牌生物相似藥，我們已經討論過這些產品，我們認為這將是我們新的成長來源。我們正在推動研發管線中數量創紀錄的潛在新藥，這些藥物針對的是當今社會面臨的一些最普遍、最昂貴和最嚴重的疾病。我認為，本季我們的財務實力再次得到體現，我們穩定的現金流將使我們能夠繼續投資於業務，同時也能為股東帶來有意義的回報，並為患者帶來變革性的創新。最後，我要感謝我們全體員工，他們全心投入我們的使命中，感謝他們為我們2019年所取得的良好開端所做的工作。我們期待在 ASCO 投資者會議上與各位交流，然後在 7 月的第二季電話會議上與大家見面。謝謝。

Great. Thanks, everybody. If you have any follow-on questions, if we didn't get to your question or if you have comments you would like to discuss, feel free to reach out to me or other members of my team. Thanks, again.

偉大的。謝謝大家。如果您有任何後續問題，或者我們沒有解答您的問題，或者您有任何意見想要討論，請隨時與我或我的團隊其他成員聯繫。再次感謝。

Ladies and gentlemen, this does conclude Amgen's First Quarter 2019 Financial Results Conference Call. We thank you greatly for your participation. You may now disconnect.

女士們、先生們，安進公司2019年第一季財務業績電話會議到此結束。非常感謝您的參與。您現在可以斷開連線了。