2023年1月9日

潛水簡報:Arrowhead Pharmaceuticals公司周一報告稱，該公司開發的一種實驗性rna藥物在2期臨床試驗中降低了一種罕見肝髒疾病患者的突變蛋白水平，降幅高達94%。這種藥物對肝髒瘢痕的影響不那麼明顯，50%的參與者改善了，而服用安慰劑的患者隻有38%。Arrowhead的高管還與合作夥伴武田製藥(Takeda)一起宣布了第三階段試驗的設計，該試驗的規模和持續時間將是華爾街分析師預期的兩倍。試驗設計將增加預期的研發成本，並推遲藥物的潛在市場推出。早盤交易中，箭頭科技的股價一度下跌30%，隨後有所回升。該公司去年11月報告稱，它有足夠的現金支持至少12個月的運營。Dive Insight: Arrowhead公司的藥物名為法茲西蘭(farzirsiran)，旨在治療α -1抗胰蛋白酶缺乏症，這是一種遺傳疾病，在這種疾病中，α -1抗胰蛋白酶蛋白的突變形式積聚在肝細胞中，導致纖維化和肝硬化。缺乏Alpha-1抗胰蛋白酶(AAT)已成為包括Vertex製藥公司、Dicerna製藥公司和Wave生命科學公司在內的幾家製藥公司的目標。最近，諾和諾德(Novo Nordisk)宣布收購Dicerna，葛蘭素史克(GSK)則獲得了Wave的AAT藥物的許可。周一公布的數據來自一項對42名AAT缺乏症患者的試驗，這些患者被隨機分為三組，分別服用法齊西蘭或安慰劑。 The trial’s main goal was a reduction in a key mutant form of AAT. On that measure, fazirsiran appears to help, with a median reduction of the mutant protein of 94% at the end of 48 weeks in patients given the highest dose. By comparison, those receiving a placebo had “no meaningful change,” Arrowhead said. A secondary goal was reduction by one point on a gauge of liver fibrosis called METAVIR, which researchers assessed using a liver biopsy. Fifty percent of the patients given fazirsiran reached this goal, versus 38% of placebo patients did. That finding “introduces risk” to the Phase 3 trial, Cantor Fitzgerald analyst Prakhar Agrawal wrote in a Jan. 9 note to clients. Arrowhead said the fibrosis data for the placbeo group “highlights the known variability” of liver fibrosis assessment. “With a larger sample size, like in the planned Phase 3 study, the rate of improvement in patients receiving placebo may more closely approximate results from natural history studies of untreated patients,” the company said in a statement. It’s not the first time researchers have seen disappointing results from an experimental drug for AAT deficiency. Vertex, for example, pulled the plug on one in 2021, prompting it to develop a second-generation agent . The planned Phase 3 trial will enroll 160 patients, half of whom will receive fazirsiran and half of whom will receive a placebo. The trial’s main goal will be the one-point reduction in liver fibrosis, measured after 106 weeks. Investors had been expecting Takeda, which will run the Phase 3 trial, to measure that fibrosis improvement at 52 weeks. “Thus the long duration of [the] Phase 3 trial will likely push out timelines of launch by at least one year,” Agrawal wrote.