未上市  

Hours after the pharmaceutical giant Eli Lilly announced a $1.1 billion all-cash deal to buy the small biotech Dermira , investors seem to be counting on something better coming along. But a Lilly executive says that their offer was fair.

Dermira (ticker: DERM) closed at $19.16 on Friday afternoon, 2.1% above the $18.75 per share that Lilly said in the morning it had agreed to pay for the company.

“I think they believe this was too low of a price,” Cantor Fitzgerald analyst Louise Chen said of investors she had been in touch with over the course of the day. “I think they’re trying to hold for something a little bit more than what it is.”

Chen said that the investors she was speaking with were looking for a price of between $1.5 billion and $2 billion for Dermira. Yet Lilly stood by the offer.

In an interview on Friday afternoon, Lilly senior vice president Patrik Jonsson, president of Lilly Bio-Medicines, said that the price was fair.

“We have done a very thorough assessment of Dermira, and we really believe that the price is really representing both a fair and full value of Dermira,” he said. “If you look at the 60 day volume-weighted average stock price, our price represents almost a 90% premium.”

The interest in Dermira is driven by the company’s prize asset, a promising drug called lebrikizumab, which is in a Phase 3 clinical trials for atopic dermatitis, a kind of eczema. The drug is part of a hot class of monoclonal antibody drugs called interleukin inhibitors. A similar drug, Regeneron (REGN) and Sanofi ’s (SNY) Dupixent, is on its way to mega-blockbuster status. Sanofi CEO Paul Hudson has said annual sales could hit more than $11.1 billion.

Chen said that, for big pharma companies looking to buy a drug like Dermira’s, there aren’t many options in late-stage clinical development. And Dermira’s lebrikizumab has a chance to be the best of the bunch.

“You’ve seen their competitors put out data,” Chen said. “There’s enough to show that Dermira’s product could be best in class, and I think that was really important here.”

Lilly’s Jonsson said that his company sees significant unmet need in atopic dermatitis. “If we can find an asset that really could improve the experience people have in terms of itching, we could have a significant impact on sleep disturbance” and quality of life, he said.

Jonsson said that he thinks lebrikizumab could beat out its competitors. “The driver of this has been lebrikizumab,” he said of the deal. “We believe it has the potential to be a best in class medicine.”

Jonsson declined to comment on whether Dermira had had other bidders. He wouldn’t speculate on whether other suitors might still show up.

Chen said that one logical potential buyer of Dermira could be Pfizer (PFE). In a note Friday, she wrote that among the large-cap companies she covers, Pfizer is the only one that hasn’t bought an interleukin inhibitor in atopic dermatitis, or could be interested in such a drug. Chen said that investors had been discussing other theoretical bidders, but that they are outside of her coverage universe.

Chen herself says that the price Lilly agreed to pay for Dermira didn’t seem unreasonably low to her. “I didn’t think, ‘Oh my gosh, this is so cheap,’ when I saw the deal,” Chen said. “I thought this was a good deal… Did I think this was a grossly undervalued deal? No.”

在製藥業巨頭禮來公司宣布以11億美元全現金收購小型生物技術公司Dermira之後的幾個小時，投資者似乎指望會有更好的發展。但是禮來公司的一位高管表示，他們的報價是公平的。

週五下午，Dermira（股票代碼：DERM）報收於19.16美元，較禮來公司早前表示已同意支付給該公司的每股18.75美元高出2.1％。

坎托·菲茨杰拉德（Cantor Fitzgerald）分析師路易絲·陳（Louise Chen）說：“我認為他們認為這一價格太低了。”她一直與投資者保持聯繫。 “我認為他們正在努力保留比現在更多的東西。”

陳說，與她交談的投資者正在為德米拉尋找15億至20億美元的價格。但是禮來公司堅持了這個提議。

禮來公司高級副總裁帕特里克·瓊森（Lilly Bio-Medicines）總裁在周五下午的一次採訪中說，這個價格是合理的。

他說：“我們對Dermira進行了非常徹底的評估，我們堅信價格確實代表了Dermira的公平價值和全部價值。” “如果看一下60天成交量加權平均股價，我們的價格幾乎溢價90％。”

人們對Dermira的興趣是由該公司的有價資產推動的，該資產是一種有前途的藥物，稱為lebrikizumab，該藥物正處於針對一種濕疹的異位性皮炎的3期臨床試驗中。該藥物是稱為白介素抑製劑的一類熱門單克隆抗體藥物的一部分。一種類似的藥物，再生元（REGN）和賽諾菲（SNY）的Dupixent，正在走向巨大的轟動地位。賽諾菲首席執行官保羅·哈德森（Paul Hudson）表示，年銷售額可能超過111億美元。

Chen說，對於希望購買像Dermira一樣的藥物的大型製藥公司，後期臨床開發沒有太多選擇。而且Dermira的lebrikizumab有機會成為同類中最好的。

“您已經看到他們的競爭對手發布了數據，” Chen說。 “有足夠的證據表明Dermira的產品可能是同類產品中最好的，我認為這在這裡非常重要。”

禮來公司（Lilly）的詹森（Jonsson）說，他的公司認為過敏性皮炎的需求尚未得到滿足。他說：“如果我們找到一種能夠真正改善人們瘙癢體驗的資產，我們可能會對睡眠障礙和生活質量產生重大影響。”

瓊森說，他認為左旋單抗可以擊敗其競爭對手。他談到這筆交易時說：“導致這種情況的是左旋單抗。” “我們相信它有潛力成為一流的醫學。”

瓊森拒絕評論德拉米拉是否還有其他競標者。他不會猜測其他追求者是否還會出現。

Chen說，Dermira的一個合乎邏輯的潛在買家可能是輝瑞公司。她在周五的一份報告中寫道，在她所涉足的大型公司中，輝瑞是唯一一家沒有購買過特應性皮炎白介素抑製劑或可能對這種藥物感興趣的公司。陳說，投資者一直在討論其他理論投標者，但他們不在她的研究範圍之內。

陳本人說，禮來同意為Dermira支付的價格對她來說似乎並不低。 “當我看到這筆交易時，我沒想到，‘噢，天哪，這麼便宜。’ “我認為這是一筆划算的交易……我是否認為這是被嚴重低估的交易？沒有。

—————-

www.anaptysbio.com/pipeline/etokimab/

Etokimab, 一針 第57天 ,概念性AD臨床12人(2017年公布) ,IL33 抑制標靶

EASI-50 , 75% (9/12)

EASI-75 , 42% (5/12)

股價市值上漲24億美元(8億美元漲到42億美元,2017/10~2018/03)

Etokimab, 2期300人AD ,2019年11月8日，公布臨床解盲失敗.

--------------------------------------------

ASLAN004 EASI-50 ,3/3=100% ,

EASI-70, 2/3=66% (4-6週 28-42天)

未來四週一針的潛力

重點:MOA (阻斷IL4/IL13訊號就有療效 )已被驗證

Aslan004 200mg /2~4週一針？

Lerikizumab 250mg/2週一針(三期臨床中)

Duilpumab 300mg/2週一針(上市三年)

Tralokinumab 300mg/2週一針(上月通過三期臨床)

————————————

AnaptysBio ,IL33 治療中重度異位性皮膚炎標靶發布12名概念性臨床正向數據。

股價2017年10月宣布前32美元，連漲4-5個月，漲四倍，最高128美元，從市值8億美元，漲到32億美元。

可惜前2個月，2019年11月8日公布2b/300人AD臨床解盲未過關。

股價回15美元，剩四億美元。

www.marketwatch.com/investing/stock/anab

www.google.com.tw/amp/s/www.fool.com/amp/investing/2017/10/10/heres-why-anaptysbio-inc-is-rocketing-higher-today.aspx

Here’s Why AnaptysBio Inc. Is Rocketing Higher Today

Mid-stage proof-of-concept data is having an unusually strong effect on AnaptysBio stock today.

Cory Renauer (TMFang4apples)

Oct 10, 2017 at 11:38AM

What happened

Shares of AnaptysBio Inc. (NASDAQ:ANAB), a clinical-stage biotech developing novel anti-inflammatory drugs, took flight after the company reported positive data from a clinical trial with its eczema candidate. Although it was just a 12-patient proof-of-concept study, the stock soared about 70.7% higher as of 10:15 a.m. EDT on Tuesday.

So what

Today’s excitement is due to a big hint that the company’s first-in-class IL-33 inhibitor has a shot at becoming an ultra-convenient treatment option for people with atopic dermatitis, the most common type of eczema. At an interval of 57 days after receiving a single dose of ANB020, 10 of 12 patients achieved a 50% or greater improvement. Responses also appear rapid, nine of the 12 patients had achieved a 50% improvement at the 15-day assessment.

Three scientists celebrating in a laboratory.

IMAGE SOURCE: GETTY IMAGES.

You don’t normally see a company’s market cap rise more than $500 million overnight on the back of phase 2 proof-of-concept data. Celgene and Tesaro have licensed anti-PD1 candidates from AnaptysBio, but this is the first of the company’s wholly owned new drug candidates to show it really has a shot at the big time. An estimated 3% of America’s adult population has some form of eczema, which means ANB020 has blockbuster potential if it continues to impress.

Now what

AnaptysBio will continue assessing these 12 patients up to 140 days after they were given a single dose of ANB020. In the first half of 2018, look for the initiation of a larger study with at least 200 eczema patients receiving multiple doses.

The company is also developing ANB020 for adults with severe peanut allergies, and another wholly owned psoriasis candidate, ANB019, should wrap up its first clinical-stage trial before the end of the year.

500,000人x3.6萬美元/年x80%(保險公司支付比率)x77%全年使用率=110億美元.

(異位性皮膚炎 & 哮喘市場)

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賽諾菲（Sanofi）尋找新的藍海市場時，它的重度濕疹和哮喘病傑出藥物Dupixent也有了顯著增長。該公司表示，該療法的年銷售額在達到頂峰時可能超過100億歐元（111億美元）。

Why Sanofi’s New CEO Is Trading Diabetes Drugs for Cancer Breakthroughs

By James Paton and Bloomberg

December 10, 2019

fortune.com/2019/12/10/sanofi-ceo-paul-hudson-diabetes-cancer-strategy/

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賽諾菲（Sanofi）的新任首席執行官剛上任僅三個月，他就將一把手術刀帶入了傳統的研究領域，以振興這個疲軟的法國製藥商。

這家製藥業巨頭將結束對新的糖尿病和心髒病藥物的追逐，幫助節省超過20億美元，因為保羅·哈德森（Paul Hudson）偏愛像癌症這樣的領域，這些領域已經很容易進行創新。於9月掌舵的哈德遜（Hudson）將於週二首次向投資者概述其戰略。

哈德森在與記者的電話會議上說：“我們正在部署我們認為將獲得最大回報的地方，不僅在財務上，而且在科學上。”賽諾菲股價在巴黎交易中上漲了5.4％，是六個月以來的最大漲幅。

諾華製藥（Novartis AG）的前製藥業老闆正在打破賽諾菲的過去，並樹立行業熟悉的道路：退出法國製藥商無法領先的領域，押注下一個大型藥物，特別是在新藥價格高昂的地區。

該公司週一表示，它將專注於血友病，乳腺癌，多發性硬化症和罕見疾病等領域的六種有前途的療法。賽諾菲（Sanofi）以25億美元收購Synthorx Inc.的交易也在周一公佈，這突顯了該公司雄心勃勃地建立其穩定的抗癌藥物，並在利潤豐厚的領域抓住了競爭對手默克（Merck＆Co.），羅氏（Roche Holding AG）和阿斯利康（AstraZeneca Plc）。

Sanford C. Bernstein的分析師Wimal Kapadia在一份報告中寫道：“這是一個積極的開始。” “它能解決研發引擎問題嗎？不完全是，但這是一個長期的故事。”

Hudson的務實態度將延伸到與合作夥伴Regeneron Pharmaceuticals Inc.的關係。Hudson說，一種融資方式可能是在明年年底禁售期屆滿後出售賽諾菲在Regeneron的股份。 。

他說：“隨著鎖定期滿，您的靈活性會提高。” “您無需更改任何內容，但可以選擇進行更改。我們將研究股權並決定在哪裡可以為我們作為組織帶來最佳回報。”

衰老的胰島素生產商Lantus也將不會推出名為GLP-1的實驗性糖尿病藥物，並將尋找合作夥伴efpeglenatide接管治療。

哈德森說：“做出這樣的改變對像我們這樣擁有令人難以置信的悠久歷史的公司來說並不容易。”該計劃旨在加強交付緩慢的管道，以將賽諾菲的營業利潤率提高到30％。

儘管價格上漲，競爭加劇和立法者的審查力度加大，但並非所有人都拒絕接受糖尿病。首席執行官諾斯·諾德（Novo Nordisk A / S）押注下一代GLP-1，並認為有機會向目前可用的胰島素推出“更智能”的胰島素，首席執行官拉爾斯·弗魯加德·喬根森（Lars Fruergaard Jorgensen）在接受采訪時說。

他實際上在倫敦說：“實際上仍然有一個非常有吸引力的市場。”

賽諾菲的投資者指望新任老闆解僱該公司的研究部門。自接任Olivier Brandicourt以來，Hudson面臨著有關製造糖尿病藥物和非處方藥物業務的未來以及其在基因治療領域計劃的問題。

該公司週一還表示，其消費者保健部門將獨立於其他三個部門，使其變得更加靈活，更具企業家精神。花旗分析師彼得·韋爾杜特（Peter Verdult）在給客戶的報告中寫道，該計劃標誌著“未來的潛在銷售/旋轉”。彭博新聞社援引知情人士的話報導了有關該公司業務選擇的內部討論。

賽諾菲（Sanofi）尋找新的藍海巿場時，它的重度濕疹和哮喘病傑出藥物Dupixent也有了顯著增長。該公司表示，該療法的年銷售額在達到頂峰時可能超過100億歐元（111億美元）。

在諾華，哈德森因推出牛皮癬等重磅產品Cosentyx等產品而獲得讚譽。

當他擔任該公司的最高執行官時，這家瑞士製藥商將分拆隱形眼鏡製造商愛爾康（Alcon）並放棄了一家消費者健康業務的股份，從而縮小了對癌症和其他嚴重疾病的尖端藥物的關注範圍。諾華還進行了一系列交易，包括去年以87億美元收購基因療法Zolgensma的開發商AveXis。

賽諾菲承認已經錯過了攻擊腫瘤的革命性突破的最後一波，因此已經在擴大癌症。該公司在今年早些時候任命了新的研究負責人約翰·里德（John Reed），表示將加速17種藥物計劃，幾乎一半用於腫瘤學研究，並放棄十多個正在開發中的藥物。

去年，賽諾菲與再生元一起獲得了免疫腫瘤藥物的批准，這是它的首個用於致命性皮膚癌的藥物。該公司在今年早些時候表示，預計美國監管機構將決定一種實驗性抗癌藥物伊沙昔單抗，用於多發性骨髓瘤，

Sanofi’s new chief executive, just three months into the job, is taking a scalpel to traditional areas of research to rejuvenate the sluggish French drugmaker.

The pharma giant will end its hunt for new diabetes and heart disease drugs, helping save more than $2 billion as Paul Hudson favors fields like cancer that are ripe for innovation. Hudson, who took the helm in September, is set to outline his strategy to investors for the first time on Tuesday.

“We’re deploying where we think we’ll get the best return, not just financially but scientifically,” Hudson said on a conference call with reporters. Sanofi shares rose as much as 5.4% in Paris trading, the biggest gain in about six months.

The former pharma boss at Novartis AG is breaking with Sanofi’s past and setting a course familiar to the industry: exiting fields where the French drugmaker isn’t leading the pack and betting on the next big drugs, especially in areas where new medicines command high prices.

The company said Monday it will focus on six promising therapies in areas such as hemophilia, breast cancer, multiple sclerosis and rare diseases. Sanofi’s $2.5 billion deal to buy Synthorx Inc., also unveiled Monday, underscores the company’s ambition to build up its stable of cancer medicines and catch rivals like Merck & Co., Roche Holding AG and AstraZeneca Plc in the lucrative field.

“This is a positive start,” Wimal Kapadia, an analyst at Sanford C. Bernstein, wrote in a note. “Does it fix the R&D engine problem? Not quite, but that is a longer-term story.”

Hudson’s pragmatic approach will extend to the relationship with partner Regeneron Pharmaceuticals Inc. One option to raise funds could be to sell Sanofi’s stake in Regeneron after a lock-up period expires at the end of next year, Hudson said, sending the U.S. company’s shares falling.

“As the lockup expires, your flexibility increases,” he said. “You don’t have to change anything, but you could choose to. We will look at the equity and decide where it can yield the best return for us as an organization.”

The maker of the aging insulin Lantus also won’t launch an experimental diabetes drug known as a GLP-1 and will look for a partner to take over the treatment, called efpeglenatide.

Making these changes is “not easy for a company like ours with an incredibly proud history,” Hudson said. The plan is aimed at strengthening a pipeline that’s been slow to deliver, with a view to boosting Sanofi’s operating profit margin to 30%.

Not everyone is turning their back on diabetes, even with increasing pushback on prices, tough competition and scrutiny from lawmakers. Rival Novo Nordisk A/S is betting on a next generation of GLP-1s and sees an opportunity to roll out “smarter” insulins to the ones currently available, CEO Lars Fruergaard Jorgensen said in an interview.

“There is actually still a very attractive market,” he said in London Tuesday.

Sanofi investors are counting on the new boss to fire up the company’s research operations. Since replacing Olivier Brandicourt, Hudson has faced questions about the future of businesses that make diabetes drugs and over-the-counter medicines, as well as its plans in the field of gene therapy.

The company also said Monday that its consumer-health unit will become a standalone business to make it more nimble and entrepreneurial, separate from its three other arms. The plan signals “a potential sale/spin in the future,” Peter Verdult, an analyst at Citi, wrote in a note to clients. Bloomberg News reported internal discussions over options for the business last month, citing people familiar with the matter.

While Sanofi hunts for new blockbusters, it also sees significant growth for Dupixent, its standout medicine for severe eczema and asthma. The treatment’s annual sales could exceed 10 billion euros ($11.1 billion) at their peak as its reach extends to new areas, the company said.

At Novartis, Hudson was credited with rolling out products such as the blockbuster Cosentyx for psoriasis.

While he was a top executive there, the Swiss drugmaker moved to spin off contact-lens maker Alcon and ditched a stake in a consumer-health venture, narrowing its focus on cutting-edge medicines for cancer and other serious diseases. Novartis also has made a series of deals, including the $8.7 billion purchase last year of AveXis, the developer of gene therapy Zolgensma.

Sanofi has already been expanding in cancer after acknowledging it missed out on the last wave of revolutionary breakthroughs to attack tumors. With a new research head, John Reed, the company earlier this year said it would accelerate 17 drug programs, almost half in oncology, and drop more than a dozen others under development.

Along with Regeneron, Sanofi last year won approval for an immune-oncology drug -- its first -- for a deadly form of skin cancer. The company said earlier this year it expects U.S. regulators to decide on an experimental cancer medicine, isatuximab for multiple myeloma, at the end of April.

Synthorx’s main treatment could become the foundation for the next immune oncology medicines and work in combination with the French company’s treatments, Sanofi said.

Atopic dermatitis therapy is an underserved and growing market

• Predicted to be as large as approximately $21 billion by 20271 globally • Need for new, differentiated therapies

Admiral 估 lebtrikizumab 歐洲尖峰銷售 4.5億歐元(5億美元)

AD 1800萬人

中、重度AD ,560萬人

新系統療法 424~554 千人(2026年)

11-14% of Moderate-Severe patients is expected to be treated with new systemics*

估2023年上市

醫療科技評估報告 「藥物納入全民健康保險給付建議書-藥品專用」資料摘要

財團法人醫薬品查驗中心

www3.cde.org.tw/Content/Files/HTA/藥品/2019年/135_討論案5_Dupixent.pdf

Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study

www.jaad.org/article/S0190-9622(19)32465-X/pdf

Background: Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD).

Objective: To assess the long-term safety and efficacy of dupilumab in patients with AD.

Methods: This ongoing, multicenter, open-label extension study (NCT01949311) evaluated long-term dupilumab treatment in adults who had previously participated in phase 1 through 3 clinical trials of dupilumab for AD. This analysis examined patients given 300 mg dupilumab weekly for up to 76 weeks at data cutoff (April 2016). Safety was the primary outcome; efficacy was also evaluated.

Results: Of 1491 enrolled patients (1042.9 patient-years), 92.9% were receiving treatment at cutoff. The safety profile was consistent with previously reported trials (420.4 adverse events/100 patient-years and 8.5 serious adverse events/100 patient-years), with no new safety signals; common adverse events included nasopharyngitis, conjunctivitis, and injection-site reactions. Sustained improvement was seen up to 76 weeks in all efficacy outcomes, including measures of skin inflammation, pruritus, and quality of life.

Limitations: Lack of control arm, limited number of patients with 76 weeks or longer of treatment (median follow-up, 24 weeks), and patients not receiving the approved dose regimen of 300 mg every 2 weeks.

Conclusion: The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate to severe AD. (J Am Acad Dermatol doi.org/ 10.1016/j.jaad.2019.07.074.)

Key words: atopic dermatiti

背景：中長期至重度的特應性皮炎（AD）的長期治療存在大量未滿足的需求。

目的：評估dupilumab在AD患者中的長期安全性和療效。

方法：這項正在進行的，多中心，開放標籤的擴展研究（NCT01949311）評估了成人dupilumab的長期治療，該成人先前曾參與過dupilumab AD的1至3期臨床試驗。這項分析檢查了截至數據截止時每週服用300 mg dupilumab的患者，長達76週（2016年4月）。安全是主要結果；療效也進行了評估。

結果：在1491名登記患者（1042.9患者-年）中，92.9％的患者接受了截斷治療。安全性與先前報導的試驗一致（420.4不良事件/ 100患者-年和8.5嚴重不良事件/ 100患者-年），沒有新的安全信號；常見的不良事件包括鼻咽炎，結膜炎和注射部位反應。在所有功效結果中，包括皮膚炎症，瘙癢和生活質量的測量結果，均可觀察到持續改善長達76週。

局限性：缺乏控制臂，有限數量的患者接受76週或更長時間的治療（中位隨訪期為24週），並且患者每兩週未接受300 mg的批准劑量方案。

結論：本研究的安全性和有效性概況支持dupilumab作為中長期至重度AD患者長期持續治療的作用

Which option below best describes your insurance situation?

一，私人保險I have prescription drug insurance through my employer or I have private insurance

Approximately 68% of commercially insured patients pay between $0-$100 per month for DUPIXENT, and approximately 32%* pay $100+2,† per month for DUPIXENT.

With the DUPIXENT MyWayR Copay Card, a 1-month supply of DUPIXENT can cost as little as $0.

二，公保medicare

Approximately 71% of Medicare Part D patients can expect to pay between $0-$100 per month for DUPIXENT, and 29% of Medicare Part D patients can expect to pay $100+3,* per month for DUPIXENT.

How much you pay for your prescription drugs may change throughout the year for some people with Part D insurance. You may pay more in the beginning of the year or more later in the year depending on which phase of the Part D benefit you are in.†

Some people with Part D coverage are eligible for the Extra Help4 program (also known as the Low-Income Subsidy or LIS), and they typically pay $3-$9 for their prescriptions.5 If you would like to check whether you qualify for this program and apply, please go to

三，公保 Medicaid

For most people on Medicaid, prescription drugs like DUPIXENT range from $4-$9 per month.6,* To find out if you qualify for Medicaid, or for more information about copays under Medicaid in your state, please go to www.medicaid.gov/state-overviews.

www.dupixent.com/dupixent-pricing

年療程成本三藥PK( Aslan004/Dupilumab/Lebrikizumab)模擬:

--------------------------------------------------

年療程成本Pk

ASLAN004/Dupilumab=40,627/93,405=44%

ASLAN004/Lebrikizumab=40,627/53,175=76%

———-

2b臨床結束，三期臨床開始，可更凖確估未來可能市場市佔。（二年左右)

---------------------------------------------------

至少如 Lebrikizumab , 前14週二週一針治療，16一52週 四週一針的維持。及相當療效

——————------------------------------

每年療程成本估算:PK

1.Dupilumab 300mg/2週x9次打針（0-14週) , 300mg/2週x18針(16一52週)合計 27x300mg

Dupilumab 300mg/2週 ，零售價1600美元x80%為保險公司平均成本 ,

療效IGA 0/1 =37%(三期臨床平均)

27針x1600x80%/37%=93,405美元/年

2. Lebrikizumab 250mg/2週x9針（0-14週)

lebrikizumab 250mg/4週x10針 , (16_52週) , 共19針

療效 IGA 0/1 , Q2w=44.6 %/Q4W=33.7%（二期臨床之資料)

9針x1600x250/300x80%/44.6%=21,524美元（前14週)

10針x1600x250/300x80%/33.7%=31,651美元(16~52週)

合計 21,524＋31,651 =53,175美元/年

3. 如ASLAN004, 前16週治療療程成本，每針用量在200mg /2週x8針,

後面16~52 週的維持治療 Aslan004 200mg/4週X8針 .

假設療效同Lebrikizumab

200mg/4週x10針 , (16_52週) , 共18針

療效 IGA 0/1 , Q2w=44.6 %/Q4W=33.7%

8針x1600x200/300x80%/44.6%=15,306美元（前14週)

10針x1600x200/300x80%/33.7%=25,321美元(16~52週)

合計 15,306＋25,321 =40,627美元/年

****理論上 療效ASLAN004 作用受器優於/Lebrikizumab作用在配體

****同級同機轉MOA之藥效，每mg 之單價會有相近之價格。

Dupixent標籤擴展為數千名患者打開了大門

圖片來源：賽諾菲，再生元

雅各布·貝爾（Jacob Bell）

2019年3月12日發布

 鳴叫

潛水簡介：

賽諾菲（Sanofi）和再生元（Regeneron）的Dupixent已獲得美國批准，用於治療青少年中度至重度特應性皮炎-根據賽諾菲（Sanofi）的估計，這種標籤擴展可使免疫學藥物的合格患者人數增加至少15萬。

監管者基於關鍵試驗數據做出的決定顯示，在接受Dupixent治療的患者治療16週後，其濕疹嚴重程度平均改善了66％，遠高於安慰劑組的24％。該研究還發現，與安慰劑組相比，Dupixent組的患者獲得清晰或幾乎清晰的皮膚的比例高出十倍以上。

Dupixent在美國的第一個國家批准是針對患有中度至重度特應性皮炎的成年人，賽諾菲的人口為30萬人。這家法國製藥商在其最新的收入報告中稱，患有中度至重度過敏性皮炎的美國青少年人數大約是成年人口的一半。

潛水見解：

Dupixent（dupilumab）已被證明是其兩家開發商的主要增長動力。 Regeneron的最新年度文件顯示，賽諾菲去年錄得該藥淨產品銷售額9.22億美元，較2017年增長近260％。

這種增長對賽諾菲而言尤其寶貴。賽諾菲（Sanofi）是三大糖尿病藥物生產商之一，其胰島素業務因承保範圍決定和價格壓力（尤其是與該公司最暢銷的Lantus（甘精胰島素）有關）而遭受打擊。國會對胰島素價格的審查表明，不利因素遠未結束。

賽諾菲（Sanofi）和再生元（Regeneron）希望Dupixent具有哮喘和特應性皮炎的適應症，今年有望大獲成功。這種藥物的增長一直持續到2018年初。根據投資銀行RBC Capital Markets引用的IMS數據，在3月8日當週，Dupixent的處方總數增加了7％。

隨著新標籤的擴展，賽諾菲預計將有150,000至200,000美國患者有資格使用Dupixent。法國製藥研發部門負責人約翰·里德（John Reed）在一份聲明中說，大約有50,000名美國患者接受了生物療法的治療。

隨著賽諾菲和再生元努力鎖定更多標籤擴展，該數字也可能會增加。 FDA剛剛接受了Dupixent的申請，作為對鼻息肉沒有得到充分控制的嚴重慢性鼻-鼻竇炎的成年人的附加維持治療。兩家公司還期望在未來幾年內向年輕的特應性皮炎和哮喘患者提交監管文件。

儘管Dupixent已顯示出對多種疾病的療效，但並不是許多患者的理想選擇。

例如，傑富瑞（Jefferies）在三月份的一份報告中詳細介紹了與醫生舉行的會議。一位醫生指出，在Dupixent上，成人過敏性皮炎患者中有30％至40％是無反應的，以及該藥物的給藥方式（注射）如何對許多患者產生了威懾作用，而不論他們的反應如何。

賽諾菲（Sanofi）發言人在給BioPharma Dive的電子郵件中指出，CHRONOS 3期試驗評估了Dupixent 300 mg加局部糖皮質激素的治療方案，該方案“可能更符合現實世界的數據”，發現79％的患者在接受治療後取得了臨床上有意義的反應與安慰劑相比，治療一年。

銷售實績

Dupixent /Dupilumab $百萬美元

美國 其他區 小計

2019 Q1 303.0 70.7 373.7

Q2 454.7 102.6 557.3

Q3 508.3 124.8 633.1

Q4(預估) 550.0 144.0 694.0

小計 1,816.0 442.1 2,258.1

2018 Q1 117.2 14.2 131.4

Q2 180.9 28.3 209.2

Q3 219.6 43.0 262.6

Q4 258.6 60.2 318.8

小計 776.3 145.7 922.0

2017

Q3 88.5 0.5 89.0

Q4 136.9 2.0 138.9

小計 225.4 2.5 227.9

2017/03/28 FDA核准上市

FDA 已核准Dupixent (dupilumab) 四個適應証

Jun 26, 2019 Approval FDA Approves Dupixent (dupilumab) for Chronic Rhinosinusitis with Nasal Polyposis (慢性鼻鼻竇炎伴鼻息肉)

Mar 11, 2019 Approval FDA Approves Dupixent (dupilumab) for Moderate-to-Severe (Atopic Dermatitis )in Adolescents )(12-17歲 異位性皮炎)

Oct 19, 2018 Approval FDA Approves Dupixent (dupilumab) for Moderate-to-Severe Asthma (哮喘)

Mar 28, 2017 Approval FDA Approves Dupixent (dupilumab) for Eczema (Atopic Dermatitis )

(成人異位性皮炎)

年療程成本三藥PK( Aslan004/Dupilumab/Lebrikizumab)模擬:

--------------------------------------------------

ASLAN004/Dupilumab=82,245/189000=44%

ASLAN004/Lebrikizumab=82,245/107648 =76%

———-

2b臨床結束，三期臨床開始，可更凖確估未來可能市場市佔。（二年左右)

---------------------------------------------------

至少如 Lebrikizumab , 前14週二週一針治療，16一52週 四週一針的維持。及相當療效

——————------------------------------

每年療程成本估算:PK

1.Dupilumab 300mg/2週x9針（0-14週) , 300mg/2週x18針(16一52週)合計 27針

Dupilumab 300mg/2週 ，零售價3239美元x80%為保險公司平均成本 ,

療效IGA 0/1 =37%(三期臨床平均)

27針x3239x80%/37%=189,000美元/年

2. Lebrikizumab 250mg/2週x9針（0-14週)

lebrikizumab 250mg/4週x10針 , (16_52週) , 共19針

療效 IGA 0/1 , Q2w=44.6 %/Q4W=33.7%（二期臨床之資料)

9針x3239x250/300x80%/44.6%=43,573美元（前14週)

10針x3239x250/300x80%/33.7%=64,075美元(16~52週)

合計 43573＋64,075 =107,648美元/年

3. 如ASLAN004, 前16週治療療程成本，每針用量在200mg /2週x8針,

後面16~52 週的維持治療 Aslan004 200mg/4週X8針 .

假設療效同Lebrikizumab

200mg/4週x10針 , (16_52週) , 共19針

療效 IGA 0/1 , Q2w=44.6 %/Q4W=33.7%

8針x3239x200/300x80%/44.6%=30,985美元（前14週)

10針x3239x200/300x80%/33.7%=51,260美元(16~52週)

合計 30,985＋51,260 =82,245美元/年

4.療程年成本PK

ASLAN004/Dupilumab=82,245/189000=44%

ASLAN004/Lebrikizumab=82,245/107648 =76%

****理論上 療效ASLAN004 作用受器優於/Lebrikizumab作用在配體

****同級同機轉MOA之藥效，每mg 之單價會有相近之價格。

www.drugs.com/history/dupixent.html

Development History and FDA Approval Process for Dupixent

2.要研究Lerikizumab朋友: 請參考下列

s23.q4cdn.com/229915008/files/doc_presentations/2019/Dermira-IR-Pres-Sept-2019_FINAL_92219_web.pdf

AD 的市場/Lerikizumab與其他藥競爭力分析.

生物製劑市場不只150億

---------------------------------------------------

Dupilumab 零售藥價3200美元/300mg(150mg*2)*9次 ,16週標準療程.=28,800美元

40%一年離開Dupilumab.平均約70%~80%用一年.

保險公司支付零售藥價80%給藥廠

估計

28,000美元*3療程*80%=69,120 美元/年.

每季69120/4=17,280美元

Dupiluma2019年第三季美國銷售約5.08億美元(全球6.33億美元.)

508,000,000/17,280=29,398人 .

29,398*4=117,592人/年 vs. 10,000,000人 =1.2% , 目前中重度AD美國市場滲透率

------------------------

分析師估2027年210億美元AD生物製劑全球市場,

美國約佔150億美元.(若增加到52週治療,市場會拉高到300億美元)

15,000,000,000/(28,000*80%)(16週療程)=669,642人---

美國市場(669,642/10,000,000=6.7%的使用率太低)

---------------------------

未來AD生物製劑美國市場不只150億美元,

不只669,642人會用到 中重度AD生物製劑.

ASLAN004 的未來價值 各階段市值可能變化估計如下:

1.概念性臨床成功,MOA機轉確立.

此時國際授權最新治療中-重度AD 標靶行情

前金7.5億美元. + 里程碑资金 6億美元.+銷售分潤?

(明年3-5月宣布,aslan004 概念性臨床期中報告,前二劑量200mg/250~300mg??)

(若像Xbiotech授權bermekimab, 以上扣除CSL分1.3億美元的里程碑金.

ASLAN 將有前金 :現金收入 可為7.5-1.3=6.2億美元 , )

1.概念性臨床成功,MOA機轉確立.

此時國際授權最新治療中-重度AD 標靶行情

前金7.5億美元. + 里程碑资金 6億美元.+銷售分潤?

(明年3-5月宣布,aslan004 概念性臨床期中報告,前二劑量200mg/250~300mg??)

(若像Xbiotech授權bermekimab, 以上扣除CSL分一半,

ASLAN 將有前金 :現金收入7.5/2=3.75億美元 ,所以美國分析師估ASLAN ADR 8美元,未來一年目標價,不是亂估的.)

2.Lebrikizumab2b期臨床成功 : 今年3月,Dermira 宣佈Lebrikizumab 二期AD臨床數據正向.股價增加3~4億美元.

(不用和CSL分,aslan 可能的獨亨,預計2021年底 aslan004完成二期臨床)

3.三期臨床成功 :???(預計2023年中, aslan004完成三期臨床)

4.FDA核準藥証:Dupilumab 2017年,股票 3~7月市值增加140億美元,當時市場認為高峄銷售將達50億美元.

目前已估高峄銷售110億美元.

Aslan004 可以輕易用Dupilumab 一半的療程成本，搶占市場。

以上CSL最高要分1/3 ,若估高峄銷售30億美元,

亞獅康 30x2/3*2.8=56億美元一一一巿值預估

(預計2024年年底, aslan004 取証)

****各期臨床的對照組療效超低和ASLAN004 同級的Dupilumab 相比，故未來Aslon004 AD各臨床必過關。