Assembly Bio的乙型肝炎計劃失敗，可能會導致PhII治愈，導致股

StephenW

Assembly Bio's hepatitis B program flops as a potential cure in PhII, sending shares spiraling
Max Gelman
Associate Editor

Looking for a hepatitis B cure, Assembly Biosciences $ASMB has struck out in a Phase II.

The South San Francisco-based company announced Thursday afternoon that its lead experimental drug vebicorvir, in combination with nucleoside therapy, could not keep patients disease-free after stopping treatments. In total, 39 of the 41 individuals in the open-label study relapsed, as the regimen failed to achieve a meaningful sustained virologic response.

Investors did not take too kindly to the news, hammering the biotech’s share prices after the bell. Assembly’s stock dropped as much as 40% on Thursday evening but has since leveled off to down about 35%.

The Hepatitis B patients involved in Assembly’s Phase II generally require treatments for the rest of their lives. Assembly’s theory went that if they could show enough of a prolonged response after taking patients off the program, which is separately being studied as a chronic suppressive therapy, then it could effectively function as a cure.

In order to find that out, Assembly treated their patients with the combination therapy for 12 to 18 months. Following that period, researchers stopped the treatments and evaluated the 41 patients every four weeks to see whether or not the combo was effective enough at preventing a relapse after an extended period of time.

But 33 of the 41 patients saw their hepatitis B return after the first four-week evaluation. By the 16-week mark, another six patients relapsed. Assembly had been looking for an SVR rate of at least 15% after 24 weeks, but Thursday’s results equate to a rate of less than 5%.

Though Thursday’s results are indeed a negative, Assembly’s combo still has potential as a chronic therapy, Baird’s Brian Skorney wrote in a note to investors. Seeing that the near-term cure play is now “off the table,” Skorney says Assembly can effectively pivot toward that path, but notes the upside is much more limited.

“Although the business opportunity for a chronic therapy for Hepatitis B is much less attractive than a curative regimen, we still see it as a reasonable business,” Skorney wrote.

Should Assembly take that route, Skorney predicts the therapy could reach anywhere between $500 million and $1 billion in annual sales.

Assembly has previously taken steps to turn that into a reality, inking a $540 million deal with BeiGene in July to take the vebicorvir and nucleoside combo into a Phase III for chronic suppression of Hepatitis B. The trial is expected to begin sometime in the first half of next year, and will include a group of patients who have seen only partial viral suppression after a year or more of nucleoside monotherapy.

The company is also looking into whether vebicorvir could still cure hepatitis B in a triple therapy concoction. In August, Assembly hooked onto a deal with Arbutus Biopharma and plans to launch the first Phase II next year that combines vebicorvir, nucleoside treatment and Arbutus’ RNAi therapeutic for the disease. Skorney notes the companies are still in the early developmental stages, however.
AUTHOR

StephenW

Assembly Bio的乙型肝炎計劃失敗，可能會導致PhII治愈，導致股價飆升
馬克斯·蓋爾曼
副主編

尋找乙型肝炎的方法，Assembly Biosciences $ ASMB已進入第二階段。

這家總部位於南舊金山的公司週四下午宣布，其領先的實驗藥物vebicorvir與核苷治療相結合，在停止治療後無法使患者保持無病狀態。由於該方案未能實現有意義的持續病毒學應答，因此在開放標籤研究中總共有39位患者復發了39位。

投資者對此消息並不太客氣，在敲響鐘聲之後重擊了生物技術公司的股價。 Assembly的股票在周四晚上下跌了40％，但此後一直回落至大約35％。

大會第二階段涉及的乙型肝炎患者通常需要接受餘生的治療。 Assembly的理論認為，如果他們在使患者退出該計劃後能夠表現出足夠的長期反應（正在單獨研究作為一種慢性抑制療法），那麼它可以有效地起到治愈作用。

為了找到答案，Assembly用聯合療法治療了他們的患者12到18個月。在此期間之後，研究人員停止了治療，並每四周評估了41名患者，以觀察該組合在延長時間後是否足以有效預防復發。

但是，在41位患者中，有33位在經過最初的四周評估後發現自己的乙型肝炎復發。到16週時，又有6名患者復發。大會一直希望24週後SVR至少達到15％，但周四的結果卻不到5％。

貝爾德的布萊恩·斯科尼（Brian Skorney）在給投資者的一份報告中寫道，儘管週四的結果確實是負面的，但Assembly的組合仍然具有作為長期療法的潛力。 Skorney說，看到近期的治療方法已經“脫離桌面”了，他說組裝可以有效地朝著這條道路發展，但是要注意的是上行空間要有限得多。

斯科尼寫道：“儘管慢性乙型肝炎治療的商業機會遠不及治愈方案，但我們仍然將其視為合理的商業。”

如果Assembly走這條路，Skorney預測該療法的年銷售額將達到5億至10億美元之間。

大會此前已採取措施將其變為現實，該公司在7月與百濟神州簽署了一項5.4億美元的協議，將vebicorvir和核苷組合納入III期慢性乙型肝炎抑制治療。該試驗預計於上半年開始將包括一組在經過一年或更長時間的核苷單藥治療後僅出現部分病毒抑制的患者。

該公司還正在研究韋比考韋是否仍可以通過三聯療法治療乙型肝炎。今年8月，Assembly與Arbutus Biopharma達成了一項交易，併計劃於明年啟動將vebicorvir，核苷治療和Arbutus的RNAi治療劑相結合的第一期II期。 Skorney指出，這些公司仍處於發展初期。
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