制药商将面对肥胖导致的肝脏疾病

StephenW

Drugmakers Set to Face Off Over Obesity-Led Liver Diseases
By Cristin Flanagan
November 9, 2018, 6:13 AM GMT+11 Updated on November 10, 2018, 12:13 AM GMT+11
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This weekend’s meeting of liver doctors and drugmakers in San Francisco promises fireworks where heavy- and light-weight hitters will duke it out for the title of best new molecules.

The multibillion-dollar market potential for obesity-driven liver disease has prompted biopharmaceutical companies large and small to chase after treatments. Intercept Pharmaceuticals Inc.’s Ocaliva, already prescribed for a bile-duct disorder, is seen as the most likely candidate to win first approval in the U.S. for patients with a fatty liver ailment known as NASH, or non-alcoholic steatohepatitis.

Competition isn’t far behind.

Large-caps Gilead Sciences Inc. and Novartis AG are developing therapies similar to Ocaliva, which belongs to a class of drugs known as FXR agonists. The companies will be presenting updated results at the American Association for the Study of Liver Diseases (AASLD) meeting, which kicks off Friday. Small-cap Enanta Pharmaceuticals Inc. will also present. And while initial abstracts from Gilead disappointed investors last month, some analysts see Novartis’s tropifexor as more promising.

The other battleground will be a new class of treatments known as THR-beta agonists. Results being presented by Madrigal Pharmaceuticals Inc. and Viking Therapeutics Inc. may hint at who could be the mid-cap champion.

Analysts say investors can expect to hear more at the meeting on future NASH diagnostics to find patients and how drugs for the ailment could be priced, as well as how awareness about the disease can be spread ahead of drugs reaching the market. Beyond NASH and fatty liver disease, Wall Street analysts also will be looking at results for therapies for primary biliary cholangitis (PBC) -- Ocaliva’s current indication -- as well as drugs for hepatitis B and C and primary sclerosing cholangitis (PSC).

Companies presenting data include:
Novartis

    Novartis recently joined with Pfizer to investigate combination therapies in NASH, including planned combo studies of tropifexor. Raymond James analyst Steven Seedhouse says tropifexor “looks like a competitive threat, Gilead’s GS-9674 not so much.”
    Tropifexor late-breaking poster is set to be presented Monday, Nov. 12; combination data with Allergan’s cenicriviroc on Sunday.


Gilead

    While Gilead’s GS-9674 uses a similar mechanism to Ocaliva, Roth Capital’s Yasmeen Rahimi sees the Intercept drug’s activation as potentially better. Gilead’s FXR agonist “underperforms” across several fronts with a similar safety profile, while being five years behind Ocaliva in development. Look for “further corroborating biomarker evidence of this drug’s activity and potential differentiation (or lack thereof),” RBC’s Brian Abrahams said.
    In addition to posters on GS-9674 in NASH (Friday) and PSC (Sunday), there will be results for GS-0976, hepatitis B therapies as well as Gilead’s selonsertib at a plenary session on Monday.

Intercept

    Intercept will have multiple posters at the AASLD meeting, but investors are focused on late-stage “Regenerate” study results expected early next year. While Raymond James’s Seedhouse sees the study as likely to succeed, the meeting may be negative for Intercept as there are “too many competitive developments in NASH,” including from Novartis’s FXR.

Madrigal Pharmaceuticals

    Madrigal has lost more than a third of its value since June 6, when shares hit a five-year high, as investors have questioned deal speculation and the company’s results. “We think AASLD will bring either a lack of answer, or unfavorable answers to those questions,” Seedhouse wrote. He predicts a “data gap” after the meeting as investors await late-stage results from a not-yet-started study.
    Madrigal’s Phase 2 results for MGL-3196 are due at a plenary session on Monday morning at 8:15 local time (11:15 a.m. in New York).

Viking Therapeutics

    “Data released at the conference will likely provide credence to VK2809’s safety and efficacy profile and corroborate the previously announced positive results,” William Blair’s Andy Hsieh wrote, while Seedhouse said the meeting may resolve “too good to be true” suspicions.
    Viking Phase 2 data in fatty liver disease to be presented as a late-breaker on Monday at 3pm in San Francisco

Galmed Pharmaceuticals

    Roth Capital’s Rahimi called Galmed “one of the most undervalued NASH companies,” despite the company’s “robust” results. Bears have focused on Aramchol’s failure to show a statistically significant change on a composite measure of liver disease, known as the NAFLD Activity Score. Focus will be on subgroup analyses of histology and lobular inflammation, she said.
    Galmed to make late-breaker presentation on “Arrest” results for Aramchol on Tuesday at 8am local time.

Cymabay Therapeutics

    Results from Cymabay’s seladelpar as well as the generic fenofibrate “could shape the competitive landscape” for Ocaliva in PBC, Abrahams of RBC wrote. The company will be presenting late-breaking abstracts on seladelpar on Monday afternoon in San Francisco and host a related reception later that evening.

Arrowhead Pharmaceuticals

    Hepatitis B could gain more attention after Johnson & Johnson’s deal with Arrowhead, JMP’s Liisa Bayko said. Other companies in the space that may be affected by results at the meeting include Assembly Biosciences, Spring Bank Pharmaceuticals and Alnylam Pharmaceuticals.
    Arrowhead late-breakers on its hepatitis B assets to be presented on Monday.

(Updates version originally run Nov. 9 to add Arrowhead section at the end.)

StephenW

制药商将面对肥胖导致的肝脏疾病
克里斯汀弗拉纳根
2018年11月9日，北京时间上午6:13 + 11更新于2018年11月10日，格林威治标准时间上午12:13 + 11


这个周末在旧金山举行的肝脏医生和制药商会议承诺举行烟花表演，重量级和轻量级的击球手将争夺最佳新分子头衔。
肥胖驱动的肝脏疾病的数十亿美元的市场潜力促使大大小小的生物制药公司追逐治疗。 Intercept Pharmaceuticals Inc.的Ocaliva已经开出胆管疾病，被认为是最有可能在美国获得脂肪肝疾病（NASH）或非酒精性脂肪性肝炎患者首次获得批准的候选药物。

竞争也不甘落后。

大型盖帽Gilead Sciences Inc.和Novartis AG正在开发类似于Ocaliva的疗法，Ocaliva属于一类称为FXR激动剂的药物。这些公司将在美国肝病研究协会（AASLD）会议上公布最新结果，该会议将于周五开始。小型公司Enanta Pharmaceuticals Inc.也将出席。虽然吉利德的最初摘要上个月让投资者感到失望，但一些分析师认为诺华的投资者更有希望。

另一个战场将是一类新的治疗方法，称为THR-beta激动剂。 Madrigal Pharmaceuticals Inc.和Viking Therapeutics Inc.提交的结果可能暗示谁可能成为中型冠军。

分析师表示，投资者可以期待在会议上听到更多有关未来NASH诊断的信息，以便找到患者，以及如何定价治疗疾病的药物，以及如何在药物进入市场之前传播对疾病的认识。除了NASH和脂肪肝之外，华尔街分析师还将研究原发性胆汁性胆管炎（PBC）治疗的结果--Ocaliva目前的适应症 - 以及乙型肝炎和丙型肝炎以及原发性硬化性胆管炎（PSC）的药物。

提供数据的公司包括：
诺华

    诺华公司最近与辉瑞公司合作研究了NASH的联合治疗，包括对tropifexor的计划性组合研究。雷蒙德·詹姆斯（Raymond James）分析师斯蒂文·赛德豪斯（Steven Seedhouse）表示，tropifexor“看起来像是一种竞争威胁，吉利德的GS-9674并非如此。”
    Tropifexor最新海报定于11月12日星期一呈现;周日与Allergan的cenicriviroc合并数据。


吉利德

    虽然Gilead的GS-9674使用与Ocaliva类似的机制，但Roth Capital的Yasmeen Rahimi认为Intercept药物的激活可能更好。吉利德的FXR激动剂在几个方面“表现不佳”，具有类似的安全性，同时比Ocaliva在开发中落后五年。寻找“进一步证实该药物活性和潜在分化（或缺乏）的生物标志物证据，”RBC的Brian Abrahams说。
    除了在NASH（星期五）和PSC（星期日）GS-9674上的海报外，周一全体会议还将有GS-0976，乙型肝炎治疗以及吉利德的selonsertib的结果。

截距

    拦截将在AASLD会议上有多个海报，但投资者关注的是明年初预计的后期“再生”研究结果。虽然雷蒙德詹姆斯的Seedhouse认为该研究可能会成功，但会议可能对Intercept不利，因为NASH的“竞争发展太多”，包括诺华公司的FXR。

Madrigal制药公司

    自6月6日股票创下五年新高以来，Madrigal已经损失了超过三分之一的价值，因为投资者质疑交易投机和公司的业绩。 “我们认为AASLD会带来缺乏答案，或对这些问题的不利答案，”Seedhouse写道。他预测会议结束后会出现“数据缺口”，因为投资者正在等待尚未开始的研究的后期结果。
    Madrigal的MGL-3196第二阶段结果将在当地时间周一上午8:15（纽约时间上午11:15）举行的全体会议上公布。

维京治疗学

    “在会议上发布的数据可能会证实VK2809的安全性和有效性，并证实了之前公布的积极结果，”William Blair的Andy Hsieh写道，而Seedhouse表示会议可能会解决“太好不可能”的怀疑。
    维京第二阶段脂肪肝病数据将于周一下午3点在旧金山作为晚期breaker出现

Galmed Pharmaceuticals

    Roth Capital的Rahimi称Galmed是“被低估的NASH公司之一”，尽管该公司的“强劲”结果。 Bears专注于Aramchol未能显示肝病综合指标的统计学显着变化，即NAFLD活动评分。她说，重点将放在组织学和小叶炎症的亚组分析上。
    当地时间周二早上8点，Aramchol对“Arestchol”的“逮捕”结果进行了晚间报道。

Cymabay Therapeutics

    RBC的Abrahams写道，Cymabay的seladelpar以及通用非诺贝特的结果“可以塑造PBC中Ocaliva的竞争格局”。该公司将于周一下午在旧金山展示最新的seladelpar摘要，并于当晚晚些时候举办相关招待会。

箭头药业

    JMP的Liisa Bayko表示，强生公司与箭头公司达成协议后，乙型肝炎可能会受到更多关注。该会议可能受会议结果影响的其他公司包括Assembly Biosciences，Spring Bank Pharmaceuticals和Alnylam Pharmaceuticals。
    星期一将报告其肝炎资产的箭头后期破坏者。

（更新版本最初运行于11月9日，最后添加了Arrowhead部分。）