With Data, Pfizer/Sangamo Step Forward in Hemophilia Gene Therapy Race

辉瑞和Sangamo治疗A型血友病基因疗法试验结果良好,缩小与BioMarin差距

2019-07-09 10:32:00 Xconomy

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Gene therapy for hemophilia is as close as it’s ever been to market. And the race to get there got more heated this past weekend at a medical meeting in Australia. At the International Society on Thrombosis and Haemostasis meeting in Melbourne, Pfizer and partner Sangamo Therapeutics (NASDAQ: SGMO) disclosed the latest results from an early-stage study, Alta, of a gene therapy for hemophilia called SB-525. The treatment is one of three in human testing for hemophilia A, the most common form of the chronic blood disease. The most advanced gene therapy, from BioMarin Pharmaceutical (NASDAQ: BMRN), could be on the market next year. Pfizer and Sangamo’s results, while early, are promising: 10 patients were treated with one of four different doses of SB-525, and the higher the dose, the more clotting protein their bodies are producing. Notably, the two patients treated with the highest dose of SB-525 are making “normal” levels of Factor VIII, the protein hemophilia A patients lack, roughly six months after treatment. Two other patients given the same dose within the last two months “appear consistent” with the others, Pfizer and Sangamo said in a statement. None of those patients have had the serious bleeding events that hemophilia patients can suffer, nor have they needed other drugs to help boost their Factor VIII levels. Pfizer and Sangamo reported one serious side effect: one patient had low blood pressure and a fever six hours after treatment, and was later discharged from the hospital. But the treatment was “generally well tolerated,” the companies said in their statement. Thus far no patients’ immune systems have neutralized the treatment—something that has been seen in studies of other hemophilia gene therapies. The results have led the FDA to grant Pfizer/Sangamo a regenerative medicine advanced therapy, or RMAT designation, which speeds up the review of an experimental gene therapy. Cross-trial comparisons come with plenty of caveats, and SB-525 is well behind hemophilia A gene therapies from BioMarin and Spark Therapeutics (NASDAQ: ONCE). But nonetheless Jefferies analysts Maury Raycroft noted that, at the highest dose, the SB-525 is “tracking better” than its rivals. SB-525 is “still early but very intriguing, and merits close monitoring given [the BioMarin program’s] promising but admittedly imperfect product profile,” wrote Stifel analyst Paul Matteis, in a research note. “The data are thus far a clear win for SB-525 and Pfizer/Sangamo,” he wrote. Sangamo shares climbed almost 17 percent on the news. Hemophilia affects an estimated 20,000 people in the US and 400,000 worldwide, and hemophilia A is the most common form. It is typically treated with two or three self-injections a week of replacement factor VIII, which helps patients prevent dangerous bleeds that can lead to joint damage and other health problems. Gene therapy offers the potential of a one-time treatment that can, ideally, rid the need for other medicines. BioMarin has estimated that its hemophilia A gene therapy, valoctocogene roxaparvovec—known in shorthand as valrox—should stop patients’ spontaneous bleeding for at least eight years. But there are questions surrounding valrox’s durability and potential reach, which has left the door open for Spark and Pfizer/Sangamo to catch up. The differences between these programs are technical, dealing with the modified viruses used to deliver the gene therapies, the amount of virus each therapy uses, and the genetic material they send into the body. SB-525, for instance, delivers less virus than Valrox, which may be playing a role in its early results, notes Jefferies analyst Raycroft. It’s important to note that while gene therapy has shown, in some cases, a stunning ability to help people with severe hemophilia produce enough clotting protein to prevent bleeds, several crucial questions remain unanswered. Responses to the gene therapies have varied—in some cases, significantly—patient to patient. It’s unclear how to tell who will respond the best, and at what point each patient will still need supplemental clotting factor on top of the gene therapy. Will some patients’ bodies neutralize the treatment? Will treatment effects wear off—especially with children—and if so, will anyone be eligible for a second dose? Those questions will take more testing to answer. But in the meantime multiple gene therapies are moving forward for both hemophilia A and the less common hemophilia B. UniQure (NASDAQ: QURE) and Spark, through a partnership with Pfizer, both have hemophilia B gene therapies in human testing. Here’s more on the shifting landscape of hemophilia treatments, and the race to treat it with gene therapy.
血友病的基因治疗和市场一样接近。上周末在澳大利亚举行的一次医疗会议上,去那里的竞赛变得更加激烈。 在墨尔本举行的国际血栓和止血协会会议上,辉瑞(Pfizer)和合作伙伴 Sangamo Therapeutics ( NASDAQ : SGMO )披露了一项名为 SB-525的血友病基因治疗早期研究的最新结果。这种治疗方法是人类检测血友病 A 的三种方法之一,血友病 A 是最常见的慢性血液疾病。最先进的基因治疗,从 BioMarin 制药( NASDAQ : BMRN ),可能在明年上市。 辉瑞( Pfizer )和三加莫( Sangamo )的研究结果虽然很早就有希望:10名患者接受了4种不同剂量 SB-525中的一种治疗,剂量越高,他们体内产生的凝血蛋白就越多。值得注意的是,两名服用剂量最高的 SB-525的患者在治疗后大约6个月,使因子 VIII (血友病 A 患者缺乏的蛋白质)水平“正常”。辉瑞(Pfizer)( Pfizer )和 Sangamo 在一份声明中表示,在过去两个月内给予相同剂量药物的另外两名患者“似乎与其他患者一致”。这些患者都没有发生血友病患者可能遭受的严重出血事件,也没有需要其他药物来帮助提高他们的第八因子水平。 辉瑞(Pfizer)和 Sangamo 报告了一个严重的副作用:一名患者在治疗六小时后出现低血压和发烧,随后出院。但两家公司在声明中表示,这种待遇“总体上是可以容忍的”。到目前为止,还没有病人的免疫系统中和了治疗,这在其他血友病基因疗法的研究中已经看到。 这一结果导致 FDA 批准辉瑞/ Sangamo 为再生医学高级治疗,或 RMAT 指定,这加快了对实验基因治疗的审查。 交叉试验比较提出了许多警告, SB-525远远落后于血友病 A 基因疗法的 BioMarin 和 Spark 疗法( NASDAQ : ONCE )。但杰富瑞分析师莫瑞•瑞克罗夫特( Maury Raycroft )指出,在最高剂量下, SB-525“比竞争对手追踪得更好”。Stifel 分析师保罗·马泰斯( Paul Matteis )在一份研究报告中写道, SB-525“仍然很早,但非常有趣,鉴于[ BioMarin 项目]前景光明,但公认不完美的产品组合,值得密切关注。” “对于 SB-525和 Pfizer / Sangamo 来说,目前的数据是一个明显的胜利,”他写道。 消息传出后, Sangamo 股价上涨了近17%。 血友病在美国大约有2万人,在全世界有40万人,血友病 A 是最常见的形式。它通常用一周两到三次自注射替代因子 VIII 来治疗,这有助于患者预防危险出血,从而导致关节损害和其他健康问题。 基因治疗提供了一次性治疗的潜力,理想情况下,可以消除对其他药物的需求。BioMarin 估计其血友病 A 基因疗法 valoctogene roxapara vovec (简称 valoctogeno )至少可以在8年内阻止患者自发出血。但围绕沃尔洛的持久性和潜在影响存在疑问,这让 Spark 和 Pfizer / Sangamo 得以迎头赶上。 这些程序之间的差异是技术上的,处理用于提供基因疗法的改良病毒,每种疗法使用的病毒数量,以及它们发送到人体的遗传物质。例如, Jefferies 分析师 Raycroft 指出, SB-525的病毒比 Valrox 少,后者可能在其早期结果中发挥作用。 值得注意的是,虽然基因疗法已经证明,在某些情况下,惊人的能力,帮助严重血友病的人生产足够的凝血蛋白质,以防止流血,几个关键问题仍然没有答案。对基因疗法的反应各不相同——在某些情况下,很明显——病人。目前还不清楚如何判断谁会做出最好的反应,在基因治疗的基础上,每个病人还需要补充凝块因子。一些患者的身体是否会使治疗无效?治疗效果是否会减弱——尤其是对儿童——如果是这样的话,任何人都有资格获得第二次剂量吗? 这些问题需要更多的测试才能回答。但与此同时,针对血友病 A 和较不常见的血友病 B 的多基因疗法正在向前发展。 UniQure ( NASDAQ : QURE )和 Spark 通过与辉瑞(Pfizer)公司的合作,在人体试验中都有血友病 B 基因疗法。这更多的是关于血友病治疗的变化,以及用基因疗法治疗血友病的竞赛。

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