2 Blockbuster Gene Therapy Programs to Watch in 2019

诺华 Zolgensma 生物制剂有望年底获批,预期每年创造10亿美元收入

2019-04-02 07:55:00 Motley Fool


There are so many companies trying doing something with gene therapy right now that trying to keep track of them all is a full-time job. If you're short on time but you still want to know which way the wind's about to blow for the overall gene therapy space, here's some good news: You can narrow your focus to two potential blockbusters. We'll probably see new drug approvals for Zolgensma from Novartis (NYSE: NVS) and Lentiglobin from bluebird bio (NASDAQ: BLUE) before the end of the year, and both drugs are expected to generate more than $1 billion annually within several years. Unfortunately, the gene therapy space has a pretty lousy track record when it comes to big expectations. Can either of these players buck the trend? Here's what you need to know about the challenges ahead. Image source: Getty Images. Last year, Novartis bought AveXis for $8.7 billion to get its hands on Zolgensma, an experimental gene therapy formerly known as AVXS-101. The Swiss pharmaceutical giant was attracted to stellar results this treatment produced for infants born with a progressive neuromuscular disorder called spinal muscular atrophy (SMA). Around 90% of children born with type 1 SMA don't reach their second birthday without the help of a ventilator, because they've lost the strength to breathe. Zolgensma is a one-time infusion that places a functional copy of the mutated gene SMA patients inherit, which appears to work better than anyone imagined.  All 15 patients treated with Zolgensma were alive and breathing on their own 24 months after just one infusion. Children born with SMA type 1 almost never develop the ability to sit up on their own, but 11 out of 12 who received the proposed dosage going forward could sit unassisted for more than five seconds. With such a strong benefit, Clarivate Analytics thinks annual Zolgensma sales could reach $1.47 billion in 2021 and $2.09 billion in 2023. Reaching such heights would probably inspire pharma giants to reach for more midsized acquisitions of gene therapy start-ups.  Image source: Getty Images. Until recently, this experimental therapy has been known as LentiGlobin because it uses a lentivirus to insert functional hemoglobin genes into stem cells that produce new blood cells. This treatment could be used for patients with transfusion-dependent thalassemia (TDT) and sickle cell disease (SCD). Both of these conditions are caused by dysfunctional genes for hemoglobin, the protein in red blood cells that carries oxygen to tissues that need it. Recently, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommended conditional approval of Zynteglo for TDT patients who can't find a matched stem cell donor. If the European Commission follows CHMP's opinion, as it usually does, this will be the first available treatment for TDT besides frequent blood transfusions, which are painful, inconvenient, and expensive. If approved in the EU in the first half of 2019, and the U.S. in 2021, annual Zynteglo sales could reach $1.12 billion in 2023. Partly because it looked extremely effective in the Northstar-2 study, where 10 out of 11 treated patients had stopped receiving blood transfusions and had hemoglobin levels up near the normal range after three months. Around 60,000 people inherit some form of beta-thalassemia, and a large portion of this population could be eligible for treatment with Zynteglo. That's probably enough to drive blockbuster sales on its own, and approval for SCD down the line could push this gene therapy even further. In the U.S. alone, there are about 100,000 people living with SCD, and perhaps a million worldwide that could use a treatment option. Misformed hemoglobin causes red blood cells to flatten out in a way that isn't helpful. Sickle-shaped blood cells get stuck in blood vessels, effectively strangling the organs they service and causing a great deal of pain along the way.  Image source: Getty Images. In theory, these treatments can save insurers and the governments that end up paying for them heaps of money. There's only one other SMA treatment available, Spinraza from Biogen (NASDAQ: BIIB) and it costs $750,000 for the first year, then $375,000 each subsequent year for life. With this in mind, the Institute for Clinical and Economic Review thinks Novartis could charge $2 million for Zolgensma, and it would still cost less than Spinraza treatment over the course of a patient's lifetime. Blood transfusions for the treatment of beta-thalassemia aren't cheap, either. Bluebird thinks Zynteglo can save payers around $2.1 million. Bluebird and Novartis will probably launch their drugs with list prices around $1 million and a pay-as-you-go model that breaks the cost into a series of annual payments. Since those payments end as soon as patients need to rely on different treatments again, there's a lot less risk. Long-term installment plans seem like an easy solution for the pricing problem that single-administration cures present, but nothing changes as quickly as it should in healthcare. So far, drug launches for expensive single-administration treatments haven't lived up to expectations. Zynteglo and Zolgensma have a better chance than buck the trend than any before them. If bluebird and Novartis can't convince end payers their therapies are worth enormous sums, though, the entire gene therapy stock universe could implode.
现在有很多公司都在尝试用基因疗法做一些事情,试图跟踪这些事情都是一份全职工作。如果你时间不长,但你仍然想知道风对整个基因治疗空间的影响,这是个好消息:你可以把注意力集中在两个潜在的重磅炸弹上。 在年底前,我们可能会看到诺华(Novartis)公司( NYSE : NVS )和蓝鸟生物公司( NASDAQ : BLUE )的 Lentigolopin 公司对 Zolgensma 的新药批准,这两种药物预计将在几年内每年产生超过10亿美元的收入。不幸的是,基因治疗领域有一个非常糟糕的记录,当谈到巨大的期望。 这两个球员中的任何一个能逆势而动吗?这里是你需要知道的关于未来的挑战。 图片来源: Getty Images 。 去年,诺华(Novartis)以87亿美元收购了 AveXis 公司,以获得 Zolgensma 的控制权。 Zolgensma 是一种实验基因疗法,以前被称为 AVXS-101。这位瑞士制药巨头被恒星结果所吸引,这种治疗方法是为患有进行性神经肌肉萎缩症(脊肌萎缩症, SMA )的婴儿生产的。 大约90%的1型 SMA 患儿在没有呼吸机的帮助下无法达到第二个生日,因为他们失去了呼吸的力量。Zolgensma 是一种一次性输注,它将变异基因 SMA 患者遗传下来的功能拷贝置于其中,这似乎比任何人想象的都要好。 所有15例接受 Zolgensma 治疗的患者在一次注射后24个月内都活着呼吸。患有 SMA 类型1的儿童几乎从未发展过独自坐姿的能力,但是12个接受了建议剂量的儿童中有11个可以坐5秒以上。 Clarivate Analytics 认为,凭借如此强劲的收益, Zolgensma 的年销售额在2021年可能达到14.7亿美元,2023年可能达到20.9亿美元。达到这样的高度可能会激励制药巨头寻求更多的中型收购基因治疗初创企业。 图片来源: Getty Images 。 直到最近,这种实验疗法一直被称为 LentiGlobin ,因为它使用 lentivirus 将功能性血红蛋白基因插入产生新血液细胞的干细胞。这种治疗方法可用于输血依赖型地中海贫血( TDT )和镰状细胞病( SCD )患者。这两种情况都是由血红蛋白的功能失调基因引起的,血红蛋白是红细胞中携带氧气到需要氧气的组织的蛋白质。 最近,欧洲药品管理局药品人类使用委员会( CHMP )建议,对于无法找到匹配的干细胞供体的 TDT 患者,有条件地批准 Zyntello 。如果欧盟委员会像往常一样遵循 CHMP 的意见,这将是除了频繁输血外, TDT 的第一个可用治疗方法,这是痛苦、不便和昂贵的。 如果2019年上半年获得欧盟批准,2021年获得美国批准,那么2023年 Zyntello 的年销售额将达到11.2亿美元。部分原因是它在 Northstar-2研究中非常有效,在接受治疗的11名患者中,有10人在三个月后停止接受输血,血红蛋白水平接近正常范围。 大约6万人继承了某种形式的β-地中海贫血,其中很大一部分人有资格接受 Zyntello 的治疗。这可能足以单独推动畅销产品的销售,而 SCD 的批准可能会进一步推动这种基因治疗。 仅在美国,就有大约10万人与 SCD 生活在一起,也许全世界有100万人可以选择治疗。错误形成的血红蛋白会导致血红细胞扁平,这是没有帮助的。镰状血细胞被卡在血管里,有效地扼杀它们所服务的器官,并在此过程中造成大量的痛苦。 图片来源: Getty Images 。 从理论上讲,这些治疗方法可以拯救保险公司和最终为它们支付巨额资金的政府。只有另外一种 SMA 疗法可用,来自百健(Biogen)公司的 Spinraza (纳斯达克代码: BIIB )和它的第一年花费了75万美元,然后每年的生命费用是375000美元。考虑到这一点,临床和经济评估研究所认为,诺华(Novartis)公司可能会为佐尔根瘤收取200万美元的费用,而且在病人的一生中,它的费用仍然低于斯宾拉莎的治疗。 用于治疗β-地中海贫血的输血也不便宜。Bluebird 认为 Zyntello 可以节省大约210万美元的支出。Bluebird 和诺华( Novartis )很可能会推出标价约为100万美元的药品,并推出一种现收现付模式,将成本分成一系列年度支付。因为一旦患者需要再次依赖不同的治疗,这些付款就会结束,风险就会大大降低。 长期分期付款计划看起来像是一个简单的解决定价问题的单一管理解决方案,但没有任何变化,应尽快在医疗保健。到目前为止,昂贵的单一管理治疗药物的上市并没有达到预期。Zyntello 和 Zolgensma 比以往任何时候都更有可能逆势而行。如果蓝鸟和诺华(Novartis)不能说服最终支付者他们的治疗价值巨大,然而,整个基因治疗股票宇宙可能崩溃。