美國安進 (AMGN) 2001 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to the Amgen first quarter year 2001 earnings conference call. During the presentation all participants will be in a listen only mode. Afterwards you will be invited to participate in the question & answer session. At that time, if you have a question, you will need to press the 1 followed by the 4 on your telephone. As a reminder, this conference is being recorded Thursday, April 26th, 2001. I would now like to turn the conference over to Mr. Kevin Sharer, Chairman and CEO of Amgen. Please go ahead sir.

女士們，先生們，謝謝你們的支持。歡迎參加 Amgen 2001 年第一季度收益電話會議。在演示過程中，所有參與者都將處於只聽模式。之後，您將被邀請參加問答環節。屆時，如果您有任何問題，您需要先按電話上的 1，然後再按 4。提醒一下，本次會議將於 2001 年 4 月 26 日星期四錄製。現在我想將會議轉交給 Amgen 董事長兼首席執行官 Kevin Sharer 先生。先生，請繼續。

Thank you. Good afternoon. I'm Kevin Sharer, Amgen's Chairman and Chief Executive Officer. I would like to welcome you to Amgen's first quarter 2001 conference call. With me today are George Morrow, Executive Vice President Sales And Marketing; Roger Perlmutter, Executive Vice President, Research and Development; Kate Falberg, Senior Vice President and Chief Financial Officer; George Morstyn, Senior Vice President, Development and Chief Medical Officer; and Cary Rosansky, Senior Director, Investor Relations. I will provide an overview of the quarter, then George Morrow will review more specifics on the commercial aspects of our business, and Roger Perlmutter and George Morstyn will review clinical progress. Then we'll take your questions. First I need to make some cautionary statements. When we estimate revenues, operating margins, capital expenditures, cash, and other financial metrics, and discuss expected legal arbitration, political, regulatory, or clinical results, such estimates and results are forward-looking statements, and of course no assurance can be given that the estimates will be accurate, and actual results could vary. Please refer to Amgen's most recent 10K report for additional information on the uncertainties and risk factors related to our business. If you have not received our press release, please call Denise [_______________] at 805-447-3433, and she will 00:02:0 resend it. If you have further questions after the conference call, please contact our investor relations group at 805-447-4634. This conference call is being web cast via the Amgen homepage and will be archived for 72 hours following the call. I'll begin with an update on the status of our worldwide regulatory approvals for ARANESP. In the United States, we're in label discussions with the FDA, and we are confident that ARANESP is close to approval. As we reported previously, we received a positive recommendation from the European Committee on Proprietary Medicinal Products, CPMP, for the approval of ARANESP, the treatment of anemia in patients with chronic renal failure. We expect that the European Commission will ratify this approval in the second quarter. George Morrow and I just returned from Europe where we reviewed the launch plans. In Germany, which is the largest EU market with erythropoietin sales in 2000 of $240 million, and the UK where 2000 erythropoietin sales were 65 million, we're ready to launch immediately following approval. Our pipeline continues to progress, and I'm pleased to announce that the BLA for Pegfilgrastim, our sustained duration form of Neupogen, was submitted to the FDA in March. Also, during the quarter, we started Phase III studies of KGF's and mucositis associated with chemotherapy, and we submitted the supplemental data to the FDA for IL-1ra to treat rheumatoid arthritis. Roger and George will speak in greater detail about these and other pipeline advancements, later. Now let's turn to the financial results. Total products sales were 798 million, an increase of 14% over the first quarter last year, and earnings per share for the first quarter was ¢28, an increase of 12% over the same period a year

謝謝你。下午好。我是安進公司的董事長兼首席執行官 Kevin Sharer。歡迎大家參加 Amgen 2001 年第一季度的電話會議。今天和我在一起的是銷售和營銷執行副總裁 George Morrow； Roger Perlmutter，研發執行副總裁；高級副總裁兼首席財務官 Kate Falberg； George Morstyn，高級副總裁、開發和首席醫療官；和投資者關係高級總監 Cary Rosansky。我將提供本季度的概述，然後 George Morrow 將回顧我們業務的商業方面的更多細節，Roger Perlmutter 和 George Morstyn 將回顧臨床進展。然後我們會回答你的問題。首先，我需要做一些警告性聲明。當我們估計收入、營業利潤率、資本支出、現金和其他財務指標，並討論預期的法律仲裁、政治、監管或臨床結果時，此類估計和結果是前瞻性陳述，當然不能提供任何保證估計是準確的，實際結果可能會有所不同。有關與我們業務相關的不確定性和風險因素的更多信息，請參閱安進公司最近的 10K 報告。如果您沒有收到我們的新聞稿，請致電 805-447-3433 致電 Denise [_____________]，她將在 00:02:0 重新發送。如果您在電話會議後還有其他問題，請致電 805-447-4634 聯繫我們的投資者關係小組。此電話會議通過安進主頁進行網絡直播，並將在電話會議後存檔 72 小時。我將首先更新我們對 ARANESP 的全球監管批准的狀態。在美國，我們正在與 FDA 進行標籤討論，我們相信 ARANESP 即將獲得批准。正如我們之前報導的那樣，我們收到了歐洲專利藥品委員會 CPMP 的積極建議，要求批准 ARANESP 治療慢性腎功能衰竭患者的貧血。我們預計歐盟委員會將在第二季度批准這一批准。 George Morrow 和我剛從歐洲回來，我們在那裡審查了發射計劃。德國是最大的歐盟市場，2000 年促紅細胞生成素的銷售額為 2.4 億美元，而英國 2000 年促紅細胞生成素的銷售額為 6500 萬美元，我們準備在獲得批准後立即推出。我們的管道繼續取得進展，我很高興地宣布 Pegfilgrastim 的 BLA 已於 3 月提交給 FDA。此外，在本季度，我們開始了 KGF 和與化療相關的粘膜炎的 III 期研究，我們向 FDA 提交了 IL-1ra 治療類風濕性關節炎的補充數據。稍後，Roger 和 George 將更詳細地介紹這些和其他管道改進。現在讓我們來看看財務結果。產品總銷售額7.98億，比去年一季度增長14%，一季度每股收益28美分，比去年同期增長12%

ago. Last fall, based on industry experience, our financial guidance for the year assumed that the FDA would approve ARANESP within a 15-month timeframe after filing. Today we are adjusting our financial guidance to reflect the second quarter approval, which lowers this year sales and earnings estimates, but has no effect on our long-term outlook. We now expect total product sales and earnings per share, excluding nonrecurring items, to grow at a low double-digit rate in 2001. Now George Morrow will speak about the commercial dynamics of our business and most importantly the pending ARANESP launch. George?

前。去年秋天，根據行業經驗，我們當年的財務指南假設 FDA 將在提交申請後的 15 個月內批准 ARANESP。今天我們正在調整我們的財務指導以反映第二季度的批准，這降低了今年的銷售和盈利預期，但對我們的長期前景沒有影響。我們現在預計 2001 年的產品總銷售額和每股收益（不包括非經常性項目）將以低兩位數的速度增長。現在喬治·莫羅將談論我們業務的商業動態，最重要的是即將推出的 ARANESP。喬治？

Thanks Kevin. One of the reasons I joined Amgen was the promise of our new products and the benefits they can provide to patients. The challenge to bring to market up to 4 new products over the next couple of years, I have to say, is a marketer's dream. I've launched a lot of products, and I think I know what it takes to get new therapeutics to market, described by physicians, and reimbursed by payers. Our sales and marketing teams around the world have been working diligently, long before Kevin ever approached me for this job. And I have to say I'm very impressed by the progress made, and I'm absolutely convinced that we're ready to meet the challenges and opportunities ahead of us. ARANESP in particular has all the markings of a blockbuster drug. We are entering a large, growing, and relatively under-penetrated anemia market with great potential to expand. I also believe this product has meaningful clinical benefits over erythropoietin. There is no question that Amgen is ready to launch ARANESP. The rate of uptake will depend on the timing of obtaining reimbursement in various segments and markets. As Kevin mentioned, we can launch in Germany and UK as soon as approval is ratified by the EC, while launch schedules in other EU markets will be staggered as reimbursement becomes available. Now I'll review our sales performance last quarter and our expectations

謝謝凱文。我加入安進的原因之一是我們新產品的承諾以及它們可以為患者提供的好處。在未來幾年內將多達 4 種新產品推向市場的挑戰，我不得不說，是營銷人員的夢想。我已經推出了很多產品，我想我知道如何將新療法推向市場，由醫生描述，並由付款人報銷。我們在世界各地的銷售和營銷團隊一直在努力工作，早在 Kevin 找我做這份工作之前很久。我不得不說，我對所取得的進展印象深刻，我絕對相信我們已經準備好迎接擺在我們面前的挑戰和機遇。特別是 ARANESP 具有重磅炸彈藥物的所有標記。我們正在進入一個龐大的、不斷增長的、相對滲透率較低的貧血市場，具有巨大的擴張潛力。我還相信該產品比促紅細胞生成素具有更有意義的臨床益處。毫無疑問，Amgen 已準備好推出 ARANESP。吸收率將取決於在各個細分市場和市場中獲得報銷的時間。正如 Kevin 提到的，我們可以在 EC 批准批准後立即在德國和英國推出，而在其他歐盟市場的推出時間表將隨著報銷的到來而錯開。現在我將回顧我們上個季度的銷售業績和我們的期望

going forward. Epogen sales of $503 million increased by 14% in the first quarter versus the prior year. We believe that growth in demand slowed somewhat to a high single to low double-digit growth rate and that reported growth rate benefited from a year-over-year wholesaler inventory change. According to our surveys, average weekly Epogen doses in hemoglobin levels have remained relatively constant. Also, recent USRDS and Amgen market research data suggest that the growth rate of dialysis patients may be slower than we previously estimated, in the 5%-6% range, instead of 6%-7%. Longer-term, patient growth, higher hemoglobins, and inflation related price increases are the key drivers to dialysis sales growth. We continue to pursue initiatives to improve ESRD patient longevity and to explore the potential clinical benefits of higher hemoglobins. Our new guidance for the combined Epogen and ARANESP sales growth rate in 2001 is low teens. There are 3 main components to this revision. First, our forecast for non-dialysis sales in the US is reduced due to the longer than planned FDA approval timeline. We now expect sales of ARANESP in new markets to be $100-150 million this year. Our prior guidance was 150-200 million. The second component is the expected delay in the ESRD uptake and related wholesaler stocking of ARANESP as a result of the longer than planned FDA approval. When factored in with the third component of lower than expected dialysis patient growth in 2001, our US dialysis business is now expected to grow at a mid to high single-digit rate. Our previous guidance was low double-digit growth. Neupogen

往前走。第一季度 Epogen 銷售額為 5.03 億美元，同比增長 14%。我們認為需求增長有所放緩，從高個位數到低兩位數增長率，報告的增長率得益於批發商庫存的同比變化。根據我們的調查，血紅蛋白水平的平均每週 Epogen 劑量一直保持相對穩定。此外，最近的 USRDS 和 Amgen 市場研究數據表明，透析患者的增長速度可能比我們之前估計的要慢，在 5%-6% 的範圍內，而不是 6%-7%。長期、患者增長、更高的血紅蛋白和與通貨膨脹相關的價格上漲是透析銷售增長的主要驅動力。我們繼續尋求改善 ESRD 患者壽命的舉措，並探索更高血紅蛋白的潛在臨床益處。我們對 2001 年 Epogen 和 ARANESP 合併銷售增長率的新指導是低十幾歲。本次修訂有 3 個主要組成部分。首先，由於 FDA 批准的時間比計劃的要長，我們下調了美國非透析藥物銷售額的預測。我們現在預計今年 ARANESP 在新市場的銷售額將達到 100-1.5 億美元。我們之前的指導是150-2億。第二個組成部分是由於 FDA 批准的時間比計劃的時間長，導致 ESRD 吸收和 ARANESP 的相關批發商庫存的預期延遲。當考慮到 2001 年透析患者增長低於預期的第三個組成部分時，我們的美國透析業務現在預計將以中高個位數的速度增長。我們之前的指導是兩位數的低增長。紐普生

sales for the first quarter were 294 million, an increase of 18% versus the prior year. We believe that demand continues to grow at a mid single-digit rate. The difference between reported sales growth and demand was primarily due to wholesaler inventory changes and to a lesser extent the negative impact of a stronger dollar on international sales. We continue to expect Neupogen sales to grow at a high single-digit rate in 2001. We are working with physicians to help them recognize patients who are at risk of febrile neutropenia to ensure that they receive Neupogen support from the first cycle of chemotherapy at the appropriate dose for their weight and until their neutrophil count has returned to normal levels. Longer term, we expect Pegfilgrastim will significantly grow the oncology franchise when approved, due to the important potential benefits of once per cycle dosing compared to daily dosing of Neupogen.

第一季度銷售額為2.94億美元，同比增長18%。我們認為需求將繼續以中等個位數的速度增長。報告的銷售增長與需求之間的差異主要是由於批發商庫存變化以及美元走強對國際銷售的負面影響。我們繼續預計 2001 年 Neupogen 的銷售額將以個位數的高增長率增長。我們正在與醫生合作，幫助他們識別有發熱性中性粒細胞減少症風險的患者，以確保他們從第一個化療週期開始就獲得 Neupogen 支持根據他們的體重給予適當的劑量，直到他們的中性粒細胞計數恢復到正常水平。從長遠來看，我們預計 Pegfilgrastim 在獲得批准後將顯著增加腫瘤特許經營權，因為與 Neupogen 的每日給藥相比，每週期給藥一次的重要潛在益處。

Thanks George. Now Roger will provide an update on our progress with regulatory filings. Roger?

謝謝喬治。現在羅傑將提供我們在監管備案方面的最新進展。羅傑？

Thanks Kevin. Let me begin by stating that the FDA review of ARANESP for nephrology indications is unquestionably on track. We've had productive discussions with senior representatives of the FDA, have a good process, and as Kevin mentioned, we're actively discussing the ARANESP label. I believe that ARANESP is close to approval in the United States for the treatment of anemia in patients with chronic renal failure. We expect to file for a label extension in the US for the use of ARANESP in oncology this year. Significant data were recently published in a supplement to the April 17 issue of the British Journal of Cancer, including a comprehensive review of the preclinical and clinical data regarding the use of ARANESP to treat anemia in the oncology setting. On March 19th, we announced that the European CPMP unanimously recommended approval of ARANESP for the treatment of anemia associated with chronic renal failure in adult and pediatric patients, 11 years old and older. The product label is expected to allow for treatment with ARANESP by subcutaneous or intravenous administration for patients in 2

謝謝凱文。首先讓我聲明，FDA 對 ARANESP 腎病適應症的審查毫無疑問正在進行中。我們與 FDA 的高級代表進行了富有成效的討論，有一個很好的過程，正如凱文提到的，我們正在積極討論 ARANESP 標籤。我相信 ARANESP 在美國接近批准用於治療慢性腎功能衰竭患者的貧血。我們預計今年將在美國申請將 ARANESP 用於腫瘤學的標籤延期。重要數據最近發表在英國癌症雜誌 4 月 17 日的增刊中，包括對關於使用 ARANESP 治療腫瘤學貧血的臨床前和臨床數據的全面審查。 3 月 19 日，我們宣佈歐洲 CPMP 一致建議批准 ARANESP 用於治療成人和 11 歲及以上兒童慢性腎功能衰竭相關貧血。產品標籤預計允許 2 歲以下患者通過皮下或靜脈內給藥進行 ARANESP 治療

circumstances, the correction of anemia and the maintenance of hemoglobin levels. Patients who ordinarily receive recombinant human erythropoietin, 2 or 3 times weekly, may change to ARANESP once weekly, and those maintained on recombinant human erythropoietin once weekly may change to ARANESP once every 2 weeks. Upon ratification of the CPMP's recommendation, the EMEA will issue a single license for marketing throughout the European Union. During the first quarter, the BLA for the use of Anakinra IL-1ra, to treat patients with rheumatoid arthritis, was supplemented with additional data, including analyses of two ongoing studies on nearly 1900 patients. As we reported last quarter, these analyses confirm the results seen in earlier studies of high level of statistical significance. We expect regulatory response from the FDA in the second half of this year. As Kevin announced earlier, the BLA for Pegfilgrastim was submitted to the FDA at the end of the first quarter. This license application included two Phase III clinical trials and was our first fully electronic submission. We expect to file in Europe in the second quarter. We believe Pegfilgrastim provides an important potential benefit of once per cycle dosing compared to daily dosing, which may improve dosing compliance by minimizing missed doses over weekend; reduce the burden on patients, care givers, and healthcare providers due to fewer clinic visits; and improve quality of life due to a major reduction in the number of injections. In addition, there may be less requirement for physician monitoring with Pegfilgrastim due to self regulation of the circulating levels of the drug. As was mentioned on the last earnings call, the NDA for abarelix, trade name Plenaxis, has been accepted for priority review by the FDA, indicating a 6-month review process through an action letter. We expect to receive FDA approval by yearend.

情況下，糾正貧血和維持血紅蛋白水平。通常每週接受 2 次或 3 次重組人促紅細胞生成素的患者可以每週一次換用 ARANESP，而每週一次接受重組人促紅細胞生成素的患者可以每 2 週換用一次 ARANESP。在批准 CPMP 的建議後，EMEA 將頒發單一許可證，在整個歐盟進行營銷。在第一季度，使用 Anakinra IL-1ra 治療類風濕性關節炎患者的 BLA 補充了額外的數據，包括對近 1900 名患者進行的兩項正在進行的研究的分析。正如我們上個季度報告的那樣，這些分析證實了早期研究中的結果具有高度統計意義。我們預計 FDA 將在今年下半年做出監管回應。正如 Kevin 早些時候宣布的那樣，Pegfilgrastim 的 BLA 已於第一季度末提交給 FDA。該許可申請包括兩項 III 期臨床試驗，是我們首次提交完全電子化的申請。我們預計將在第二季度在歐洲提交申請。我們認為，與每日給藥相比，Pegfilgrastim 提供了每週期給藥一次的重要潛在益處，這可以通過最大限度地減少週末錯過的劑量來提高給藥依從性；由於門診次數減少，減輕了患者、護理人員和醫療保健提供者的負擔；並由於注射次數的大幅減少而提高生活質量。此外，由於藥物循環水平的自我調節，對醫生監測 Pegfilgrastim 的要求可能較低。正如在上一次財報電話會議上提到的，abarelix 的 NDA（商品名 Plenaxis）已被 FDA 接受優先審查，通過行動函表明需要 6 個月的審查過程。我們希望在年底前獲得 FDA 的批准。

Now George will provide you with an update on some of Amgen's clinical development programs and data to be presented at ASCO next month. George?

現在，George 將為您提供有關 Amgen 的一些臨床開發計劃和數據的最新信息，這些計劃和數據將在下個月的 ASCO 上展示。喬治？

Thanks Kevin. In the first quarter KGF progressed to a Phase III clinical trial following the successful completion of Phase II studies. The Phase III clinical trial will evaluate the effectiveness of

謝謝凱文。在第一季度，KGF 在成功完成 II 期研究後進入了 III 期臨床試驗。 III期臨床試驗將評估其有效性

KGF to reduce oral mucositis in patients with hematological malignancies, undergoing transplantation. Mucositis is a serious side effect of cancer treatments such as high-dose chemotherapy and/or radiotherapy that patients undergoing transplantation receive. These treatments are often toxic to the mucosal cells lining the mouth and the gastrointestinal tract, resulting in ulceration of the mucosal lining. Oral mucositis results in painful sores in the mouth that may prevent patients from eating. Patients frequently require pain medication and have reduced quality of life. Also, during the quarter, data was presented at the first international workshop on lipoatrophic diabetes on the use of mainly leptin to treat patients with congenital lipodystrophy. There are several forms of lipodystrophy, including congenital and acquired forms. Lipodystrophy is characterized by generalized or partial loss of body fat. In severe cases, it is associated with metabolic disorders such as insulin resistance, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia. Although the study was conducted on a small patient sample, preliminary data from the study show that leptin may be safe and effective in reversing the diabetes and elevated triglycerides observed in these patients. Early in the first quarter, it was reported that the trials of BDNF in ALS had not demonstrated any therapeutic benefit. All clinical development of BDNF has been discontinued. Now I'd like to turn to the Annual Meeting of the American Society of Clinical Oncology to be held in San Francisco in the first part of May, which will be a major meeting for Amgen. Abstracts from a number of Amgen's product candidates have been accepted for presentation. Phase III data will be presented for the first time for ARANESP in the oncology setting and for Pegfilgrastim, the sustained duration form of Neupogen. The first presentation of Phase II data for KGF will also be made. Five abstracts on ARANESP have been accepted as posters to be presented at ASCO.

KGF 可減少接受移植的惡性血液病患者的口腔粘膜炎。粘膜炎是癌症治療的嚴重副作用，例如接受移植的患者接受的高劑量化學療法和/或放射療法。這些治療通常對口腔和胃腸道內層的粘膜細胞有毒，導致粘膜內層潰瘍。口腔粘膜炎會導致口腔疼痛，患者可能無法進食。患者經常需要止痛藥並且生活質量下降。此外，在本季度，關於主要使用瘦素治療先天性脂肪代謝障礙患者的第一屆脂肪萎縮性糖尿病國際研討會上公佈了數據。脂肪代謝障礙有多種形式，包括先天性和後天性。脂肪代謝障礙的特徵是身體脂肪的普遍或部分減少。嚴重者與胰島素抵抗、高血糖、高膽固醇血症、高甘油三酯血症等代謝紊亂有關。儘管該研究是針對小樣本患者進行的，但該研究的初步數據表明，瘦素可能安全有效地逆轉在這些患者中觀察到的糖尿病和甘油三酯升高。第一季度初，據報導 BDNF 在 ALS 中的試驗未顯示出任何治療益處。 BDNF 的所有臨床開發都已停止。現在我想談談將於 5 月上旬在舊金山舉行的美國臨床腫瘤學會年會，這將是 Amgen 的一次重要會議。來自 Amgen 的許多候選產品的摘要已被接受進行展示。 III 期數據將首次在腫瘤學環境中呈現 ARANESP 和 Neupogen 的持續持續時間形式 Pegfilgrastim。還將首次展示 KGF 的 II 期數據。五篇關於 ARANESP 的摘要已被接受為將在 ASCO 上展示的海報。

These abstracts demonstrate the broad program Amgen is pursuing in oncology. Data will be presented from studies in patients with solid tumors and hematologic malignancies, and the treatment of anemia of both chronic cancer without chemotherapy and in patients receiving chemotherapy. Studies include pharmacokinetic data demonstrating the predictability of ARANESP given every 3 weeks. Data will also be presented demonstrating ability of ARANESP to be dosed every 2 weeks without loss of dose efficiency compared to weekly ARANESP. The results of a pivotal Phase III clinical trial, evaluating the efficacy of ARANESP in 320 patients with lung cancer receiving chemotherapy, will also be presented. The data suggests that ARANESP may be safely and effectively administered less frequently than recombinant human erythropoietin. Data from two pivotal Phase III clinical trials that evaluated Pegfilgrastim support for chemotherapy treatment of patients with breast cancer will also be presented at ASCO. In one study, the safety and efficacy of once per cycle administration of Pegfilgrastim dosed at 100 mcg/kg of bodyweight were evaluated in one of the studies in 310 patients with stage II-IV breast cancer. A second Phase III study in 157 patients with Stage II-IV breast cancer compared a fixed dose of 6 mg of Pegfilgrastim delivered once per chemotherapy cycle with Neupogen administered daily at 5 mcg/kg of body weight. These studies demonstrated that once per cycle Pegfilgrastim was comparable to daily Neupogen in reducing the duration of severe neutropenia following myelosuppressive chemotherapy and that the tolerability of Pegfilgrastim was similar to daily Neupogen. A single fixed dose of Pegfilgrastim was comparable to a median of 10 daily injections of Neupogen. Once-per-cycle administration of Pegfilgrastim has the potential to simplify the management of chemotherapy-induced neutropenia and may improve dosing compliance and convenience for patients

這些摘要展示了安進在腫瘤學領域所追求的廣泛計劃。將提供來自實體瘤和血液系統惡性腫瘤患者的研究數據，以及未經化療和接受化療的慢性癌症患者貧血治療的數據。研究包括藥代動力學數據，證明每 3 週給予一次 ARANESP 的可預測性。還將提供數據，證明與每週 ARANESP 相比，ARANESP 每 2 週給藥一次而不會損失劑量效率。還將公佈一項關鍵的 III 期臨床試驗的結果，該試驗評估了 ARANESP 在 320 名接受化療的肺癌患者中的療效。數據表明，與重組人促紅細胞生成素相比，ARANESP 的給藥頻率可能較低且安全有效。兩項評估 Pegfilgrastim 對乳腺癌患者化療的支持的關鍵 III 期臨床試驗的數據也將在 ASCO 上公佈。在一項研究中，在 310 名 II-IV 期乳腺癌患者中的一項研究中評估了每週期一次給予 Pegfilgrastim 劑量為 100 μg/kg 體重的安全性和有效性。在 157 名 II-IV 期乳腺癌患者中進行的第二項 III 期研究比較了固定劑量的 Pegfilgrastim（每個化療週期給藥一次）與每天以 5 mcg/kg 體重給藥的 Neupogen。這些研究表明，每週期一次 Pegfilgrastim 在減少骨髓抑制化療後嚴重中性粒細胞減少的持續時間方面與每日 Neupogen 相當，並且 Pegfilgrastim 的耐受性與每日 Neupogen 相似。單次固定劑量的 Pegfilgrastim 與每天注射 10 次 Neupogen 的中位數相當。每週期一次的 Pegfilgrastim 給藥有可能簡化化療引起的中性粒細胞減少症的管理，並可能改善患者的給藥依從性和便利性

and healthcare providers. These studies form the basis of that BLA submission. Results of two Phase II clinical trials evaluating KGF will also be presented. The first study was a double-blind, placebo controlled trial of 129 patients and evaluated the efficacy of KGF in reducing mucositis in patients with hematologic malignancies, undergoing Autologous Peripheral Progenitor Cell Transplantation after radiation-based conditioning and high-dose chemotherapy. KGF effectively reduced the duration of severe oral mucositis, improved patient-reported mouth and throat soreness, and reduced the amount of narcotic analgesia that was used. Results from this study support the further evaluation of KGF in a Phase III clinical trial that commenced in the first quarter, as announced earlier on this call. A second double-blind, placebo controlled study evaluated the efficacy of KGF in preventing chemotherapy-induced mucositis in 64 patients with advanced colorectal cancer. The results are consistent with previous clinical observations of the efficacy and safety profile of KGF to reduce the incidence and duration of chemotherapy-induced mucositis.

和醫療保健提供者。這些研究構成了 BLA 提交的基礎。還將介紹評估 KGF 的兩項 II 期臨床試驗的結果。第一項研究是一項對 129 名患者進行的雙盲、安慰劑對照試驗，評估了 KGF 在減少血液系統惡性腫瘤患者粘膜炎方面的療效，這些患者在基於輻射的調節和高劑量化療後接受了自體外周祖細胞移植。 KGF 有效地縮短了嚴重口腔粘膜炎的持續時間，改善了患者報告的口腔和喉嚨酸痛，並減少了使用的麻醉鎮痛劑的量。正如本次電話會議早些時候宣布的那樣，這項研究的結果支持在第一季度開始的 III 期臨床試驗中對 KGF 進行進一步評估。第二項雙盲、安慰劑對照研究評估了 KGF 在 64 名晚期結直腸癌患者中預防化療引起的粘膜炎的功效。結果與之前關於 KGF 減少化療引起的粘膜炎的發生率和持續時間的有效性和安全性的臨床觀察結果一致。

Thanks George. I'm enthusiastic about our new products, and I believe we have the right people in place to achieve our plans of generating 8-9 billion in sales in 2005 and growing our earnings per share at a low 20s compound annual growth rate. We hope you share our confidence and excitement about our future. Now we'll take your questions.

謝謝喬治。我對我們的新產品充滿熱情，我相信我們有合適的人選來實現我們在 2005 年實現 8-90 億美元銷售額並以 20 多歲的低複合年增長率增長每股收益的計劃。我們希望您能分享我們對未來的信心和興奮。現在我們將回答您的問題。

Ladies and gentlemen we will now begin the question and answer session. If you do have a question please press the 1 followed by the 4 on your pushbutton phone. You will hear a 3-tone prompt acknowledging your request. If your question has been answered and you would like to withdraw your polling request, you may do so by pressing the 1 followed by the 3. If you are using a speakerphone please pick up your handset before pressing the numbers. One moment please for the first question. Elise

女士們，先生們，我們現在開始問答環節。如果您有任何疑問，請按按鍵電話上的 1，然後按 4。您將聽到 3 聲提示音，確認您的請求。如果您的問題已得到回答並且您想撤回您的投票請求，您可以按 1，然後按 3。如果您使用免提電話，請在按數字之前拿起您的聽筒。請稍等一下第一個問題。愛麗絲

Wang, with Salomon Smith Barney, please go ahead.

王先生，所羅門美邦，請繼續。

Thank you. I had a couple of questions. One, this is addressed to George Morrow, if you could perhaps talk about the approach to reimbursement for ARANESP with HCFA, and what you expect, and how much time do you expect to take to achieve that? Two, just a quick question on whether or not there was a price increase and if so what it was for EPO, and then three, if you could elaborate on the regulatory timeframe for abarelix? I had thought that the PDUFA action date was actually in June.

謝謝你。我有幾個問題。第一，這是給 George Morrow 的，如果你能談談用 HCFA 報銷 ARANESP 的方法，你的期望是什麼，你希望花多少時間來實現這個目標？第二，只是一個關於是否有價格上漲的快速問題，如果是，那麼 EPO 的價格是多少，然後第三，你是否可以詳細說明 abarelix 的監管時間表？我原以為 PDUFA 行動日期實際上是在六月。

Okay. I'll take the first question. The HCFA reimbursement, I think you're talking about dialysis here, and we will initiate our formal discussions with HCFA once we get approval, and that will probably take the best of 6 months to conclude. The second question is do we have a price increase for Epogen, and yes we did last year, 3.9% in February.

好的。我先回答第一個問題。 HCFA 報銷，我想你在這裡談論的是透析，一旦獲得批准，我們將與 HCFA 進行正式討論，這可能需要 6 個月的時間才能完成。第二個問題是 Epogen 的價格是否上漲，是的，去年 2 月份上漲了 3.9%。

George you want to talk about abarelix time frame?

George 你想談談 abarelix 的時間框架嗎？

Sure. Abarelix was granted priority review by the FDA, and we're projecting that it'll be approved by year-end, which takes into account what you said.

當然。 Abarelix 獲得了 FDA 的優先審查，我們預計它會在年底前獲得批准，這會考慮到您所說的內容。

Matthew Geller with CIBC World Market. Please go ahead with your question.

Matthew Geller 與 CIBC 世界市場。請繼續你的問題。

Hi. Yes, a few more timing questions here too. Can you talk a little bit more about the process with abarelix? What's going on with it, also for endometriosis? Also what's going on with calcimimetics? And any more detail on the filing process for ARANESP for oncology and timing with the date, etc.?

你好。是的，這裡還有一些時間問題。你能多談談使用 abarelix 的過程嗎？這是怎麼回事，也是子宮內膜異位症？還有擬鈣劑是怎麼回事？還有關於 ARANESP 腫瘤學申請流程和日期時間等的更多詳細信息嗎？

Roger Perlmutter here. With respect to abarelix, I think George has indicated where we stand with respect to the review process. The issue of other potential indications for abarelix is still under review

羅傑·珀爾馬特在這裡。關於 abarelix，我認為 George 已經表明了我們在審查過程中的立場。阿巴瑞克的其他潛在適應症問題仍在審查中

within our organization. I think that that's, we are very interested, of course, in the product, and a lot of discussions are going on, and in addition, we are evaluating other clinical data. With respect to the calcimimetics program, the calcimimetics program continues in clinical trials, Phase II clinical study, and we're looking forward to having the opportunity to review these data in more detail. I think what's available has already been discussed in prior calls. And with respect to ARANESP oncology, I think George sort of reviewed the data, much of which is going to be presented at ASCO. We're awaiting the completion of these studies and then naturally we will pursue our regulatory filings very, very soon.

在我們的組織內。我認為那是，我們當然對產品非常感興趣，並且正在進行很多討論，此外，我們正在評估其他臨床數據。關於擬鈣劑項目，擬鈣劑項目繼續進行臨床試驗，II 期臨床研究，我們期待有機會更詳細地審查這些數據。我認為在之前的電話會議中已經討論過可用的內容。關於 ARANESP 腫瘤學，我認為 George 有點審查了數據，其中大部分數據將在 ASCO 上展示。我們正在等待這些研究的完成，然後我們自然會很快、很快地提交我們的監管文件。

I think Matt, it's Kevin, the timing of ARANESP in dialysis, chronic renal insufficiency, we said in comments, and I think in the press release, we believe we're very close in the United States, and in Europe, we've got a recommendation, and we think things are on track, and we believe we'll get approval in the US, second quarter.

我想馬特，我是凱文，ARANESP 在透析、慢性腎功能不全方面的時機，我們在評論中說，我認為在新聞稿中，我們相信我們在美國和歐洲非常接近，我們已經得到了建議，我們認為事情正在走上正軌，我們相信我們會在第二季度在美國獲得批准。

Maykin Ho with Goldman Sachs. Please go ahead with your question.

Maykin Ho 與高盛。請繼續你的問題。

Hi, at this point, for your guidance on ARANESP, a 100-150 million, what is the assumption for US approval and also with the general delay in FDA approval of products, why are you so confident that you can have these timelines in abarelix and also IL-1ra?

嗨，在這一點上，對於你對 ARANESP 的指導，100-150 百萬，美國批准的假設是什麼以及 FDA 批准產品的普遍延遲，為什麼你如此自信你可以在 abarelix 中擁有這些時間表還有 IL-1ra？

Those are a series of questions. Let me try to take them Maykin one at a time. We filed for ARANESP in December of 1999. At the time, the industry norm looked like, for a product of this characteristic, about a 15-month process. We made that assumption in

這是一連串的問題。讓我嘗試一次帶走他們 Maykin。我們在 1999 年 12 月申請了 ARANESP。當時，行業規範看起來，對於具有這種特性的產品，大約需要 15 個月的過程。我們在

our financial plans, but for regulatory guidance, we thought probably the first half of this year. We still believe that the first half of this year is what's going to happen in the United States for ARANESP, although that is turning out to be a few months later than we had thought in the financial area. I want to emphasize that none of this very slight delay has anything to do with the product's fundamental characteristics or any difficulties in the approval process, in fact we're in very serious discussions, and we think we're close to the end. You're right in pointing out the difficulty of predicting with precision on any product candidate, when the FDA is going to act. The FDA has got a large backlog. They have challenges, but our best judgment is the guidance we've given, and we think we owe investors that best judgment. We try to hedge enough that we don't expect that any one product, that we have at the FDA, is going to set a world's record for approval, but we do use our best judgment, and as related to IL-1ra, I'll ask George Morstyn to comment on how that product candidate is coming, George.

我們的財務計劃，但對於監管指導，我們認為可能是今年上半年。我們仍然相信，今年上半年是 ARANESP 在美國將要發生的事情，儘管事實證明這比我們在金融領域的預期晚了幾個月。我想強調的是，這種非常輕微的延遲與產品的基本特性或批准過程中的任何困難沒有任何關係，事實上我們正在進行非常認真的討論，我們認為我們已經接近尾聲。您正確地指出了在 FDA 採取行動時準確預測任何候選產品的難度。 FDA 積壓了大量工作。他們面臨挑戰，但我們最好的判斷是我們給出的指導，我們認為我們欠投資者最好的判斷。我們試圖進行足夠的對沖，以至於我們不希望我們在 FDA 擁有的任何一種產品會創造世界批准記錄，但我們確實會使用我們最好的判斷，並且與 IL-1ra 相關，我George，我會請 George Morstyn 評論該產品候選者的發展情況。

As you know, we submitted the BLA in December of '99. We had a series of questions. We've responded to those with a submission, as we mentioned today, of up to, close to 1900 patients, and what we foreshadowed here is an action letter. Obviously an action letter could be, the data is adequate, and we're into label discussions, or the action letter could be a series of greater questions, but I am confident that the data that we submitted is of high quality, shows a very significant effect of our IL-1ra, confirms the data we had previously, confirms the previous safety profile, and so I think what we are foreshadowing in this call is very achievable.

如您所知，我們在 99 年 12 月提交了 BLA。我們提出了一系列問題。正如我們今天提到的，我們已經對那些提交了多達近 1900 名患者的意見書做出了回應，我們在這裡預示的是一封行動函。顯然，行動函可能是，數據足夠，我們正在進行標籤討論，或者行動函可能是一系列更大的問題，但我相信我們提交的數據質量很高，顯示出非常我們的 IL-1ra 的顯著影響，證實了我們之前的數據，證實了之前的安全概況，所以我認為我們在這次電話會議中預示的是非常可以實現的。

Caroline

卡羅琳

Copithorne with Morgan Stanley. Please go ahead with your question.

Copithorne 與摩根士丹利。請繼續你的問題。

Hi. My question was on the EPO numbers, actually EPO and Neupogen. In both cases, while there are a few explanations that you've already given in terms of slower dialysis patient population growth, I just wanted to know, it still looks like, obviously, seasonally 1Q is usually weaker than 4Q, but we saw a pretty significant decline sequentially, and in the case of Neupogen, down from the second quarter and third quarter of last year. So just trying to figure out if there is something else that went on. If there was inventory beyond last year's Y2K portfolio or what affected that still more?

你好。我的問題是關於 EPO 編號，實際上是 EPO 和 Neupogen。在這兩種情況下，雖然您已經就透析患者人數增長放緩給出了一些解釋，但我只是想知道，顯然，季節性的第一季度通常弱於第四季度，但我們看到了連續大幅下降，就 Neupogen 而言，下降幅度低於去年第二季度和第三季度。所以只是想弄清楚是否還有其他事情發生了。如果存在超出去年 Y2K 投資組合的庫存，或者影響更大的是什麼？

This is Kevin. Let me try to give a little color on the Epogen, and I'll ask George to talk about the fundamentals of the Neupogen business. He's a little bit more up-to-date, and he's been out in the field. He's been looking at that. It's really difficult, as you point out, to predict with precision Epogen each quarter. There's lots of moving parts. There is inventory as you point out. We've also had Y2K, and it's difficult to judge exactly what's going to happen. In inventory, we've got price discounts, spillover adjustments, just a whole variety of factors, and you're right that seasonally the first quarter's been a little bit weaker. The only thing we can see in the dialysis business that is perhaps different than the past, as we pointed out, is that the patient growth rate we're now projecting is at about the 5%-6% range instead of our historical guidance in the 6%-7% range, but we don't see any other dynamics in that business that are of concern than that. And also, going forward, we're going to report ARANESP and Epogen together so that we don't cause even more problems in trying to understand what's going on. So bottom line on Epogen, so far so good. Looks like maybe patient growth rate is a tiny bit lower than we might have thought in the past, but that's it. Now

這是凱文。讓我試著給 Epogen 一些顏色，我會請喬治談談 Neupogen 業務的基本面。他比較新，而且他一直在外地工作。他一直在看那個。正如您指出的那樣，每個季度都很難準確預測 Epogen。有很多活動部件。正如您所指出的那樣，有庫存。我們也經歷過 Y2K，很難準確判斷會發生什麼。在庫存方面，我們有價格折扣、溢出調整，還有各種各樣的因素，你是對的，第一季度的季節性有點弱。正如我們所指出的，我們在透析業務中唯一可以看到的可能與過去不同的是，我們現在預測的患者增長率大約在 5%-6% 的範圍內，而不是我們在6%-7% 的範圍，但我們沒有看到該業務中任何其他令人擔憂的動態。而且，展望未來，我們將一起報告 ARANESP 和 Epogen，這樣我們就不會在試圖了解正在發生的事情時造成更多問題。所以 Epogen 的底線，到目前為止一切順利。看起來患者的增長率可能比我們過去想像的要低一點點，但僅此而已。現在

I'll let George talk about Neupogen. From a CEO's perspective, we're doing well on Neupogen, and George, what's it look like to you?

我會讓喬治談談 Neupogen。從 CEO 的角度來看，我們在 Neupogen 上做得很好，George，你覺得它怎麼樣？

Yeah, just to reiterate. First quarter sales were negatively impacted by wholesaler inventory drawdowns and foreign exchange. Inventory had a positive year-on-year impact of growth rate due to the Y2K buildup late in 1999. So the quarter that we compared to this first quarter was a light one for us. In terms of demand, we're growing in mid single-digits, and the product's performing, I think, very well given it's been on the market for 10 years.

是的，只是重申一下。第一季度銷售額受到批發商庫存減少和外彙的負面影響。由於 1999 年底 Y2K 的累積，庫存對增長率產生了積極的同比影響。因此，我們與第一季度相比的這個季度對我們來說是一個輕鬆的季度。就需求而言，我們正在以中個位數增長，而且我認為該產品的表現非常好，因為它已經上市 10 年了。

Errol Rudman with Rudman Capital Management. Please go ahead with your question.

Errol Rudman 與 Rudman Capital Management。請繼續你的問題。

Question was asked. Thank you.

有人問了問題。謝謝你。

Eric Schmidt with SG Cowen Securities. Please go ahead with your question.

SG Cowen 證券的 Eric Schmidt。請繼續你的問題。

Thanks for taking my question. Let's see, first a question for George on the KGF data coming up at ASCO, whether he could direct us at the competitive advantage for your growth factor versus that of other companies in development, and then a second question, a pipeline question on ARANESP. We've seen in the past some data from Amgen suggesting that the longer effect of the products may actually translate into an efficacy advantage, at least in oncology patients, and I'm wondering whether that's a viable label advantage for you going forward?

感謝您提出我的問題。讓我們看看，首先是喬治關於 ASCO 上出現的 KGF 數據的問題，他是否可以指導我們了解您的增長因素與其他開發中公司的競爭優勢，然後是第二個問題，關於 ARANESP 的管道問題。我們過去曾看到安進公司的一些數據表明，產品的較長療效實際上可能轉化為療效優勢，至少在腫瘤患者中是這樣，我想知道這是否是您未來的可行標籤優勢？

Thanks. In terms of the KGF, I think you're alluding to Human Genome Sciences as KGF-2 in development. I think our program is obviously very advanced. We've just started Phase III clinical trials. I think we spent a fair bit of time validating the way to measure the endpoints in the mouth, the ulcers, the endpoints to do with mucositis, and I think you'll see, when you go to ASCO, both the study that we've done in the hematologic malignancies and in the colorectal settings, that the data looks impressive, and there is no really effective treatment at the moment to prevent

謝謝。就 KGF 而言，我認為你是在暗示人類基因組科學作為開發中的 KGF-2。我認為我們的程序顯然非常先進。我們剛剛開始了 III 期臨床試驗。我認為我們花了相當多的時間來驗證測量口腔終點、潰瘍、粘膜炎終點的方法，我想你會看到，當你去 ASCO 時，我們的研究在血液系統惡性腫瘤和結直腸疾病中做過研究，數據看起來令人印象深刻，目前還沒有真正有效的治療方法來預防

mucositis. And if you talk to nurses in centers like transplant centers of chemotherapy wards, you'll see the main complaints that patients have today is to do with mucositis. So I think we're dealing with an important side effect, and we're moving very quickly. On the other issue to do with ARANESP, you will see data, I think particularly from John Glaspy, on giving ARANESP once a week, once every 2 weeks, and at different doses. And I think one important thing to pay attention to is not just the ultimate response rate, when do patients get to a normal hematocrit, but how quickly they get there, and I think the data with ARANESP particularly at the high doses is very impressive in terms of rate of response. I think when you're sick and you're anemic, you've got cancer, it's very important to have a drug that can give you a response quickly. We have, as was mentioned, one Phase III trial that's completed. I think that gives us a quick way of getting a label in the setting faster, I think, than people were expecting. We're certainly going to do other phase III trials and exploit some of these other advantages of ARANESP so that we can bring the ultimate advantage to patients who have cancer.

粘膜炎。如果您與化療病房移植中心等中心的護士交談，您會發現如今患者的主要抱怨與粘膜炎有關。所以我認為我們正在處理一個重要的副作用，我們正在迅速行動。在與 ARANESP 相關的另一個問題上，您會看到數據，我認為尤其是來自 John Glaspy，關於每週一次、每 2 週一次以及不同劑量的 ARANESP。而且我認為需要注意的一件重要事情不僅僅是最終反應率，患者何時達到正常血細胞比容，而是他們達到正常水平的速度，我認為 ARANESP 的數據特別是高劑量時非常令人印象深刻響應率方面。我認為當你生病並且貧血時，你得了癌症，擁有一種可以快速給你反應的藥物是非常重要的。如前所述，我們已經完成了一項 III 期試驗。我認為這為我們提供了一種快速獲得標籤的方法，我認為這比人們預期的要快。我們肯定會進行其他 III 期試驗，並利用 ARANESP 的其他一些優勢，以便我們可以為癌症患者帶來最終優勢。

Dennis Harp with Deutsche Banc. Please go ahead with your question.

德意志銀行的丹尼斯·哈普。請繼續你的問題。

Yes, a couple of questions on ARANESP and then on the pipeline. On ARANESP, of the 100-150 million, how of that would you estimate would be pipeline versus end market sales, pipeline spill versus end market sales? And then in Europe, you mentioned you're ready to go in Germany and the UK, do you have reimbursement there, and if not when do you expect to get reimbursement there? With regard to the pipeline, there was no mention of LymphoCide, which I think is in phase III trials. What are your expectations for LymphoCide, and will we hear about it at the ASCO meeting? And

是的，有幾個關於 ARANESP 的問題，然後是關於管道的問題。在 ARANESP 上，在 100-150 百萬中，您估計管道與終端市場銷售、管道洩漏與終端市場銷售之間的關係如何？然後在歐洲，你提到你準備去德國和英國，那裡有報銷嗎？如果沒有，你預計什麼時候在那里報銷？關於管道，沒有提到 LymphoCide，我認為它處於 III 期試驗中。您對 LymphoCide 有何期望，我們會在 ASCO 會議上聽到嗎？和

then finally on leptin, the lipodystrophy study that was done, how big of an indication is that?

最後是關於瘦素，即已完成的脂肪代謝障礙研究，這有多大意義？

I'll let the two Georges handle this. George Morstyn, why don't you take the clinical ones, and then George Morrow could take the market ones, okay?

我會讓兩個喬治處理這件事。 George Morstyn，你為什麼不拿臨床的，然後 George Morrow 可以拿市場的，好嗎？

With regard to epratuzumab, as you say it is in the clinic. It's an antibody against CD22. We are working in patients who have failed with Rituxan. We haven't really projected yet the relative pathway, as we've just licensed the product and we're doing the studies, and we're certainly proceeding with it, and we're really happy this is Amgen's first direct anticancer drug as distinct from a [_______________] care drug. With regard to leptin, the reason that we mentioned this was because it's a very clear-cut result. It was presented at a public meeting at NIH branch, NIDDK sponsored the meeting; small number of patients were treated, and however, the results were incredibly clear cut in terms of, as I mentioned, the effects on glucose tolerance, insulin insensitivity, fat storage in the liver, and while the group of congenital patients with lipodystrophy is quite small, there're probably less than 500 patients, we feel the very clear-cut demonstration of an effect in these patients who have extremely low leptin levels, and where leptin is really returning the patients back to normal, is a good proof of concept and gives us a good scientific path to follow with the further development of leptin. For example, in settings, such as where lipodystrophy associated with AIDS patients who are on protease inhibitors, and in other settings, with patients who may have lower leptin levels. So we think while the initial opportunity is small, there may be as a proof of concept indicated that the drug

關於epratuzumab，就像你說的在臨床上。它是一種針對 CD22 的抗體。我們正在研究 Rituxan 失敗的患者。我們還沒有真正預測相關途徑，因為我們剛剛獲得產品許可並正在進行研究，我們肯定會繼續進行，我們真的很高興這是安進的第一個直接抗癌藥物不同於 [_______________] 護理藥物。關於瘦素，我們之所以提到這個，是因為它是一個非常明確的結果。它在 NIH 分部的公開會議上發表，NIDDK 贊助了會議；少數患者接受了治療，但是，正如我提到的，就葡萄糖耐量、胰島素不敏感性、肝臟脂肪儲存的影響而言，結果非常明確，而先天性脂肪營養不良患者組相當很小，可能只有不到 500 名患者，我們認為對這些瘦素水平極低的患者產生了非常明確的效果，並且瘦素確實使患者恢復正常，這是一個很好的概念證明並為我們進一步開發瘦素提供了一條很好的科學路徑。例如，在諸如脂肪代謝障礙與服用蛋白酶抑製劑的 AIDS 患者相關的環境中，以及在其他環境中，與可能具有較低瘦素水平的患者相關的環境。所以我們認為雖然最初的機會很小，但可能有概念證明表明藥物

will work in other settings that we haven't yet explored.

將在我們尚未探索的其他設置中工作。

Terrence Norchi with Citibank Global Asset. . .

花旗銀行全球資產部的 Terrence Norchi。 . .

We had a, there were a couple of other questions there?

我們有一個，那裡還有其他幾個問題？

I'm sorry.

對不起。

Okay. How much inventory for ARANESP? We don't break that number out. I can tell you though that the wholesalers are anticipating huge demand. This is a very, very big market, and as demand ramps up, they will build inventories to make sure they have enough supply. The second question was about Germany and UK reimbursement, and that will be available at launch once we get the EMEA approval.

好的。 ARANESP 有多少庫存？我們不會打破這個數字。不過我可以告訴你，批發商預計會有巨大的需求。這是一個非常非常大的市場，隨著需求的增加，他們將建立庫存以確保有足夠的供應。第二個問題是關於德國和英國的報銷，一旦我們獲得 EMEA 批准，這將在發佈時提供。

Are you ready to take the next question sir?

先生，準備好回答下一個問題了嗎？

Yes, we are.

是的，我們是的。

Terrence Norchi with Citibank Global Asset Management. Please go ahead.

花旗銀行全球資產管理公司的 Terrence Norchi。請繼續。

Hi, thanks. This is Terry Norchi here. What's the outlook for continued trend of less chemotherapy on the underlying Neupogen sales, first? And then secondly, I'm wondering if you could characterize the share count expectations moving forward? And finally, if you could characterize some moving parts for the corporate revenue line? Thanks.

你好謝謝。我是 Terry Norchi。首先，潛在的 Neupogen 銷售減少化療的持續趨勢前景如何？其次，我想知道您是否可以描述未來的股票數量預期？最後，您是否可以描述公司收入線的一些活動部分？謝謝。

We think that the basic effect of the shift to less myelosuppressive chemotherapy has basically happened.

我們認為轉向較少骨髓抑制化療的基本效果已經基本發生。

George, I don't know if you've got any more color than that.

喬治，我不知道你有沒有比這更多的顏色。

Our feeling is that weekly chemo is beginning to flatten out, so we probably have the full brunt of that.

我們的感覺是每週化療開始趨於平緩，所以我們可能首當其衝。

Okay.

好的。

And Kate why don't you take the other questions?

凱特，你為什麼不回答其他問題呢？

The corporate part of revenue for the year, we expect to be pretty similar to last year's amount which was 246 million. The first quarter 51 million is lower than last year, and that's because last year we had a milestone payment from Kineret Amgen related to the NESP development program. The share count, we don't expect to see a lot of change, but there are various factors that affect that share count. One them is the stock price, and so it's difficult to predict with any precision.

今年收入的企業部分，我們預計與去年的 2.46 億美元非常相似。第一季度 5100 萬低於去年，這是因為去年我們從 Kineret Amgen 獲得了一筆與 NESP 開發計劃相關的里程碑付款。份額數量，我們預計不會有太大變化，但影響份額數量的因素有很多。其中之一是股票價格，因此很難準確預測。

Rachel Leheny with Lehman Brothers. Please go ahead with your question.

雷切爾萊赫尼和雷曼兄弟。請繼續你的問題。

Thanks. Two questions, one, with regards to the guidance of 100-150 million, can you give us a sense of what the split there will be between the US and Europe, and what you anticipate the split to be between US and Europe? And then following on, can you, with regards to the ARANESP clinical program in cancer, can you give us a sense, do you have, what your ongoing Phase III trials are? Obviously you're going to have one that you're going to discuss next week at ASCO. But what your filing plans would be in cancer, particularly in terms of the dosing schedule you would look for? Would you file on a once a week and then try to expand it later? How do you think that will, sort of, unfold?

謝謝。兩個問題，一個，關於100-1.5億的指導，你能告訴我們美國和歐洲之間會有什麼樣的分歧，你預計美國和歐洲之間的分歧是什麼？然後，關於 ARANESP 癌症臨床計劃，您能否告訴我們您正在進行的 III 期試驗是什麼？顯然，下週您將在 ASCO 上討論一個問題。但是您的癌症申請計劃是什麼，特別是在您尋求的給藥方案方面？您會每週提交一次，然後再嘗試擴展嗎？你認為這將如何展開？

Let me take Rachel the ARANESP question. The 3 basic markets, maybe 4, for ARANESP, one is Europe dialysis, the other is the US chronic renal insufficiency, then ultimately oncology, and then finally all other anemia related. The size of the market is overwhelmingly in the US, although Europe is pretty large at $800 million or so. We don't break out this 100-150 million in Europe or US or even indication, but I think by the magnitude of these markets, over time you can see where the opportunity is going to really lie, and Europe, although significant, will not be as large as the US, and George if you want to talk about the Phase III in oncology?

讓我讓 Rachel 回答 ARANESP 問題。 3 個基本市場，也許 4 個，對於 ARANESP，一個是歐洲透析，另一個是美國慢性腎功能不全，然後是腫瘤學，最後是所有其他與貧血相關的市場。市場規模絕大多數在美國，儘管歐洲相當大，達到 8 億美元左右。我們沒有在歐洲或美國突破這 100-1.5 億，甚至沒有跡象表明，但我認為根據這些市場的規模，隨著時間的推移，你可以看到真正的機會所在，而歐洲雖然重要，但也會不像美國那麼大，喬治，如果你想談談腫瘤學的第三階段？

Yeah, as I said, that at ASCO we'll be presenting the phase III trail which has once a week NESP dosing, shows it to be very effective compared to erythropoietin used in the same study. We will in addition to that, be obviously filing all of the data, other data, that we have in terms of use of NESP in patients who have cancer, and that will include the data that's being presented at this meeting by John

是的，正如我所說，在 ASCO 上，我們將展示每週一次 NESP 劑量的 III 期試驗，表明與同一研究中使用的促紅細胞生成素相比，它非常有效。除此之外，我們顯然會提交所有數據，其他數據，我們在癌症患者中使用 NESP 方面的數據，其中將包括 John 在本次會議上提供的數據

Glaspy in over 80 patients who've received NESP once every 2 weeks, in them it would also seem to be very effective, and also the data we presented previously at the American Society of Hematology where NESP was used once every 3 weeks at higher doses than the doses obviously used once a week and once every 2 weeks. In terms of what sort of label we'll get and how broad it will be based on all that data, I don't want to speculate at this stage, but clearly I think we have proof of concept for the use of NESP once a week, once every 2 weeks, and once every 3 weeks.

Glaspy 在超過 80 名每 2 週接受一次 NESP 的患者中使用，對他們來說似乎也非常有效，還有我們之前在美國血液學會上提供的數據，其中每 3 週以更高劑量使用 NESP比明顯每週使用一次和每 2 週使用一次的劑量要多。就我們將獲得什麼樣的標籤以及基於所有數據的標籤範圍而言，我現階段不想推測，但很明顯我認為我們已經有了使用 NESP 的概念證明一周一次，每 2 週一次，每 3 週一次。

[_______________] with Scudder Kemper Investments. Please go ahead.

[______________] 與 Scudder Kemper Investments。請繼續。

It's been asked and answered. Thank you.

它已被詢問和回答。謝謝你。

Thank you. Wendy Lou with Arnhold & S. Bleichroder. Please go ahead with your question.

謝謝你。 Wendy Lou 和 Arnhold & S. Bleichroder。請繼續你的問題。

Good afternoon, one question relative to ARANESP. Do you know whether or not the drug crosses the blood-brain barrier?

下午好，關於 ARANESP 的一個問題。你知道藥物是否能穿過血腦屏障嗎？

There has been some sort of preclinical studies around the effect a drug that this might have, but we don't really know whether those apply or not. We haven't done studies like that.

已經有一些關於藥物可能產生的影響的臨床前研究，但我們真的不知道這些是否適用。我們沒有做過那樣的研究。

Okay, thank you.

好的謝謝你。

David Gruber with Lehman Brothers. Please go ahead with your question.

戴維·格魯伯 (David Gruber) 與雷曼兄弟 (Lehman Brothers)。請繼續你的問題。

Yeah, two questions. One is, is HCFA reimbursement essential for ARANESP use in dialysis and eventually oncology? And the second question is, in your opinion, is the very strong growth exhibited by Procrit in oncology more a reflection of higher dosing than it is of market penetration? And what is your estimate regarding the oncology patient penetration to be at the moment?

是的，兩個問題。一是，HCFA 報銷對於 ARANESP 在透析和最終腫瘤學中的使用是否必不可少？第二個問題是，在您看來，Procrit 在腫瘤學領域表現出的強勁增長是否更多地反映了更高的劑量而不是市場滲透？您對目前腫瘤患者滲透率的估計是多少？

We'd probably, rather not comment on a market we're not in, other than to say we believe that anemia in oncology is a very large market. It has a lot of growth yet to go, and we're anxious to participate.

我們可能寧願不對我們不在的市場發表評論，只是說我們相信腫瘤學貧血是一個非常大的市場。它還有很大的發展空間，我們很想參與其中。

In terms of HCFA

在 HCFA 方面

reimbursement, for CRI, Medicare is about half of the market, little less than half of the market, and we should get coverage righted approval. The question will be claims processing, and that's really up to the carriers and in the physicians' offices and the fiscal intermediaries and possible outpatient. So it'll be there, the coverage will be there. The claims processing will be slow, but by creating enough demand, we'll work our way through that.

報銷，對於 CRI，Medicare 大約佔市場的一半，略低於市場的一半，我們應該獲得覆蓋權的批准。問題將是索賠處理，這實際上取決於承運人、醫生辦公室、財政中介機構和可能的門診病人。所以它會在那裡，報導會在那裡。索賠處理會很慢，但通過創造足夠的需求，我們將努力解決這個問題。

Stu Weisbrod with Merlin BioMed Group. Please go ahead.

Merlin BioMed Group 的 Stu Weisbrod。請繼續。

Hi, just a few questions left, all on the pipeline. First, when will we see the bone metastasis data for Osteoprotegerin? And, can you also give us an update on the immunophilin program? And what's left to do in the calcimimetic program before you start Phase III?

嗨，只剩下幾個問題，都在準備中。首先，我們什麼時候能看到骨保護素的骨轉移數據？而且，您能否也給我們介紹一下免疫親和素計劃的最新情況？在開始 III 期之前，擬鈣劑項目還需要做什麼？

In terms of OPG, we are in a Phase I type II study in oncology, as I've mentioned before, because of the [_______________] the hurdle here is pretty high in terms of getting a drug that's more convenient, has clear clinical benefit, and so we haven't foreshadowed yet, moving into Phase II, exactly how we will do that. We're trying to make sure that we have the right molecule to take forward successfully. With regard to neuroimmunophilins, we're in the middle of a Phase II program in Parkinson's disease. And, third program on, the calcimimetic program, we've mentioned that we had to work on, sort of, the formulation and manufacturing program for the tablets, and that's going really well. So that we took into Phase III tablets that we could actually then be confident that we could manufacture when the drug was approved. We also are in phase II doing a dose-finding study to make sure that we've really optimized the dose we

就 OPG 而言，正如我之前提到的，我們正在進行腫瘤學的 I 期 II 型研究，因為 [____________] 在獲得更方便、具有明顯臨床益處的藥物方面，這裡的障礙非常高，所以我們還沒有預示進入第二階段，我們將如何做到這一點。我們正在努力確保我們擁有正確的分子來成功推進。關於神經免疫親和素，我們正處於帕金森病的 II 期項目中。第三個計劃是擬鈣劑計劃，我們已經提到我們必須在某種程度上研究藥片的配方和製造計劃，而且進展非常順利。這樣我們就進入了 III 期藥片，我們實際上可以確信我們可以在藥物獲得批准時生產。我們還在 II 期進行劑量探索研究，以確保我們真正優化了劑量

take into phase III. So the program is moving, as Roger said previously, really well. One of the interesting things I think is that, I was at the National Kidney Foundation last week and calcimimetics really is a major advance for patients with renal osteodystrophy. Dr. [_______________] presented the impact of hyperparathyroidism, hypercalcemia, the effect on coronary artery disease, and I think the most promising drug in development at the moment is at calcimimetic program. So we're certainly trying to move it as fast as we can.

進入第三階段。正如羅傑之前所說，該計劃進展順利。我認為有趣的事情之一是，上週我在國家腎臟基金會，擬鈣劑確實是腎性骨營養不良患者的重大進步。 [______________] 博士介紹了甲狀旁腺功能亢進、高鈣血症、對冠狀動脈疾病的影響，我認為目前最有希望開發的藥物是擬鈣劑項目。所以我們當然會盡可能快地推動它。

Eric Ende with Banc of America Securities. Please go ahead with your question.

美國銀行證券公司的埃里克·恩德 (Eric Ende)。請繼續你的問題。

Thanks for taking my call, my question. I have a few questions, first on ARANESP and then a quick one on Neupogen. Can you talk a little bit about the process of getting NESP on the formulas at the hospitals, and also the timing associated with that? And then if you can kind of, take a shot at this one, off-label versus on-label use of ARANESP. And the third thing, do you yet have the data to determine what the once every 3-week dosing will be for ARANESP? And then I'll ask you the Neupogen question in a minute.

感謝您接聽我的電話，我的問題。我有幾個問題，首先是關於 ARANESP 的問題，然後是關於 Neupogen 的快速問題。你能談談醫院將 NESP 加入配方奶粉的過程，以及與之相關的時間安排嗎？然後，如果可以的話，嘗試一下 ARANESP 的標示外使用與標示內使用。第三件事，你是否有數據來確定 ARANESP 每 3 週一次的劑量是多少？然後我會在一分鐘內問你 Neupogen 問題。

Why not just ask it now so we'll get them all.

為什麼不現在就問，這樣我們就能得到它們。

Okay. When I look at the numbers just over time, Neupogen sales have been declining since the third quarter, and I think you guys are saying that there is still an inventory drawdown, is that correct?

好的。當我看過去的數字時，Neupogen 的銷售額自第三季度以來一直在下降，我想你們是在說庫存仍在減少，對嗎？

Yeah, I'll let George Morrow take all these and. . .

是的，我會讓喬治莫羅承擔所有這些。 . .

Wait, wait, and let me actually continue the thought. You did 294 million this quarter, and you're talking about high single-digit growth. So are you expecting some, looks like pretty explosive growth off of the first quarter and the second, third, and fourth, to get to those kind of numbers, and I'm just trying to get a sense as to whether or not that's achievable.

等等，等等，讓我繼續這個想法。你這個季度做了 2.94 億，而且你在談論高個位數的增長。那麼你是否期待第一季度和第二、第三和第四季度出現一些看起來非常爆炸性的增長，以達到這些數字，我只是想了解這是否可以實現.

Let me take that question. We had 18% growth in the first quarter, and we're predicting high single digit growth for Neupogen throughout the year, which really reflects an underlying growth rate in the mid single-digits, and we think the demand is there for that. Does that answer your question?

讓我來回答這個問題。我們在第一季度實現了 18% 的增長，我們預計 Neupogen 全年將實現高個位數增長，這確實反映了中等個位數的潛在增長率，我們認為需求是存在的。這是否回答你的問題？

Yeah, but I'm also trying to understand why it's declining for 2 quarters in a row if it's just an inventory drawdown. It had to be a lot of inventory.

是的，但我也試圖理解為什麼它連續兩個季度下降，如果它只是庫存減少的話。它必須有很多庫存。

Well, the first quarter again had an inventory drawdown. It just wasn't as deep as the inventory drawdown in the first quarter of 2000. So we had a price increase on Neupogen in November of last year. There's naturally an inventory buildup around that time, so we have a buyout period. It just was shallower than the previous year, and so that will slightly pump our Neupogen growth rate for the entire year. I think you can, sort of, count on a mid single-digit rate in terms of underlying demand for the product, sale or demand.

好吧，第一季度再次出現庫存縮減。它只是沒有 2000 年第一季度的庫存減少那麼嚴重。所以我們在去年 11 月對 Neupogen 進行了提價。那個時候自然會有庫存增加，所以我們有一個買斷期。它只是比前一年淺，因此這將略微提高我們全年的 Neupogen 增長率。我認為你可以在某種程度上依靠產品、銷售或需求的潛在需求方面的中個位數增長率。

Okay, let's go to the ARANESP questions then.

好的，那麼讓我們轉到 ARANESP 問題。

Okay, in terms of getting ARANESP on formulary, we're already working with hospitals. Obviously we have a great value proposition for this product, and we have a great sales force, we have excellent corporate account management, in fact we've built that team up over the last few years. And so we really think we've got a great story to tell. This will of course take some time depending on the hospital, but we'll be there in the end. In terms of off-label use, I'm sure there'll be some, but we really don't want to comment on that.

好的，就將 ARANESP 納入處方集而言，我們已經在與醫院合作。顯然，我們對這個產品有很大的價值主張，我們有強大的銷售隊伍，我們有優秀的公司客戶管理，事實上我們在過去幾年裡建立了這個團隊。所以我們真的認為我們有一個很棒的故事要講。這當然需要一些時間，具體取決於醫院，但我們最終會到達那裡。在標籤外使用方面，我相信會有一些，但我們真的不想對此發表評論。

It's basically impossible to predict, and we of course cannot market directly off-label. There will be some periodicals, and I'm sure there'll be a lot of interest. And the last question I know you had was data, whether we have and if so, when we'll show it on the once every 3 week dosing, and George Morstyn can comment.

這基本上是不可能預測的，我們當然不能直接在標籤外銷售。會有一些期刊，我相信會有很多興趣。我知道你的最後一個問題是數據，我們是否有，如果有，我們什麼時候會在每 3 週一次的劑量上顯示它，George Morstyn 可以發表評論。

We presented some data on that at the American Society of Hematology

我們在美國血液學會提供了一些相關數據

Meeting. If you don't have the abstract, I'm sure Cary could send it to you if you call him later. We're not presenting any other data at the ASCO meeting on once every 3-week dosing. That's obviously something we continue to look at.

會議。如果您沒有摘要，我相信如果您稍後打電話給 Cary，他可以將其發送給您。我們不會在 ASCO 會議上提供每 3 週給藥一次的任何其他數據。這顯然是我們繼續關注的事情。

We've got time for one more question.

我們還有時間再問一個問題。

Thank you sir. The final question will come from Meirav Chovav with CS First Boston. Please go ahead.

謝謝你，先生。最後一個問題將來自 CS First Boston 的 Meirav Chovav。請繼續。

Thank you. My question is, when you are designing the ARANESP trials in oncology, are you going to obviously, from the data we've seen so far, efficacy is highly dependent on dose. So would one of your goals would it be to design a pivotal trial such that in theory you can get label or a result that has higher efficacy than Procrit? And also an unrelated question, relating to leptin; as far as I remember, you were developing 2 derivative forms of leptin which were supposed to overcome the issue of the fact that you couldn't give enough leptin to actually get overweight people to lose weight. I think it worked if you didn't need to lose weight because the heavier the person was the more leptin they needed. So I was wondering if you can update us on the status of a dose trial, on the second generation leptin. Thanks.

謝謝你。我的問題是，當你設計 ARANESP 腫瘤學試驗時，你是否會明顯地從我們目前看到的數據來看，療效在很大程度上取決於劑量。那麼，您的目標之一是設計一項關鍵試驗，以便在理論上您可以獲得比 Procrit 具有更高功效的標籤或結果嗎？還有一個不相關的問題，與瘦素有關；據我所知，你正在開發 2 種衍生形式的瘦素，它們應該可以克服你無法提供足夠的瘦素來真正讓超重的人減肥這一事實的問題。我認為如果您不需要減肥，它會起作用，因為人越重，他們需要的瘦素就越多。所以我想知道你是否可以向我們更新第二代瘦素劑量試驗的狀態。謝謝。

This is Roger. I'll take those two. First of all, clearly we want to develop ARANESP at its most effective dose for its indications, and as you indicated, of course the response is dose dependant. It is always a balance in terms of efficacy, getting maximal efficacy and at the same time ensuring that we have the minimal efficacious dose well defined. So part of the effort, of course, in a well-designed Phase III study as you recognize is to bracket those doses and make sure that we understand what the appropriate dose recommendation should be; something, which

這是羅傑。我要拿那兩個首先，很明顯，我們希望以最有效的劑量開發 ARANESP，正如您所指出的，當然，反應是劑量依賴性的。它總是在功效方面取得平衡，獲得最大功效，同時確保我們有明確定義的最小有效劑量。因此，當然，正如您所知，在精心設計的 III 期研究中，部分努力是將這些劑量括起來，並確保我們了解適當的劑量建議應該是什麼；某事，哪個

thereafter is discussed in detail with the FDA. That's perhaps all we need to say about the design of those Phase III studies. With respect to leptin, we continue to be interested in the range of indications for leptin both in its traditional form and also in modified versions, which have different pharmacokinetic profiles. We are studying leptin to ask the question of whether or not it would be useful in the context of either those who have managed to reduce weight by other programs in terms of maintaining weight or to directly cause weight loss. We're still in the process of analyzing these data, and we hope to be able to come to a conclusion about the broader utility of leptin in the relatively near future.

隨後與 FDA 進行詳細討論。關於那些 III 期研究的設計，也許這就是我們需要說的全部內容。關於瘦素，我們繼續對瘦素的適應症範圍感興趣，包括傳統形式和修飾形式的瘦素，它們具有不同的藥代動力學特徵。我們正在研究瘦素，以詢問它是否對那些通過其他計劃在保持體重方面成功減輕體重或直接導致體重減輕的人有用。我們仍在分析這些數據，我們希望能夠在不久的將來就瘦素的更廣泛用途得出結論。

Okay, thank you very much. We appreciate your interest today, and we look forward to the future. Thanks a lot.

好的，非常感謝。感謝您今天的關注，我們期待著未來。非常感謝。

Ladies and gentleman that does conclude your conference for today. You may all disconnect, and thank you for participating.

女士們先生們，今天的會議結束了。你們都可以斷開連接，感謝你們的參與。