Etranacogene dezaparvovec

据Endpoints最近披露的数据，目前全球十大最昂贵的基因疗法共有77个在研同类竞品，其中48个来自中国，数量是美国在研项目的两倍以上，更是欧洲的7倍。 在基因治疗领域，几乎所有靶点都有来自中国的强劲对手。 Zynteglo（每次治疗费用280万美元）、Elevidys（每次320万美元）、Roctavian（每次290万美元）和Casgevy（每次220万美元）都面临着至少七家中国竞争对手的挑战。Lenmeldy（425万美元）是榜单上最昂贵的疗法，其竞争对手全部来自中国，而美国和欧洲暂无同类竞品。 在所有基因疗法中，仅有一款欧美在研竞品数量超过中国，即治疗镰状细胞贫血的Lyfgenia。即便如此，中国企业相关在研项目也占了竞争赛道的三分之一以上。 文章还提到，来自西方的基因疗法正处于脆弱时期。BioMarin公司2月24日宣布，因未能找到买家，将把其A型血友病药物Roctavian撤出市场。UniQure公司治疗B型血友病的药物Hemgenix的市场推广也十分缓慢，截至去年12月仅有75名患者接受了治疗。 其他第一代基因疗法大多仅在富裕国家使用，或面临临床效果不及预期的处境。与此同时，全球的支付方持续抵制数百万美元的单次治疗定价。基因疗法“用单次治疗替代终身慢性治疗”以支撑其高昂价格的经济逻辑尚未完全实现。 而在中国，去年4月获批的信念医药自主研发用于治疗B型血友病的基因疗法信玖凝，定价约为35万美元，仅为美国同类基因疗法价格的十分之一。 目前，至少有34家中国制药企业正在研发榜单上十大基因疗法的同类项目，其中一些企业同时针对不同的疾病靶点开展多项研发工作。 中国在基因治疗领域的竞争站位正在不断提升。 拓展阅读 单次治疗、长期获益，基因治疗补足血友病群体缺失的人生“拼图” 总第2799期 访问研发客网站，深度报道和每日新闻抢鲜看 www.PharmaDJ.com

Last April, Chinese regulators approved Belief BioMed’s gene therapy for the bleeding disorder hemophilia B, setting up a challenge to one of the priciest medicines. The treatment marked the first hemophilia gene therapy in China to be developed and manufactured entirely by a domestic company. Belief BioMed priced it at $350,000, one-tenth the cost of a rival therapy that sells for $3.5 million in the US. In the year since, it’s become clear that Belief BioMed’s approval is a bellwether: In a global race to develop cheaper and potentially better alternatives to the world’s 10 most expensive medicines, China has pulled ahead. An Endpoints News analysis of clinical trial databases shows that China accounts for 48 of the 77 programs targeting this group of ultra-expensive gene therapies. China’s total is more than double the number in the US and seven times as many as Europe. Even if only a fraction of these lower-cost alternatives reach the market, it could upend the economics of a gene therapy system built on multimillion-dollar prices. Shanghai-based Belief BioMed’s 161,000-square-foot facility — the equivalent of three football fields — stands as tangible proof that China’s gene therapy ambitions have gone beyond lab science and into industrial execution. The company plans to dose its first commercial hemophilia B patient this month, and it’s working to secure approval in the US and additional countries. “​​We want to be a global gene therapy company,” said Xiao Xiao, the co-founder and chief science officer of Belief BioMed. “No drug is only for one nation.” In its expansive pipeline, the company is also conducting clinical trials of two therapies that could compete with top-priced therapies for hemophilia A and the rare disorder Duchenne muscular dystrophy. Belief BioMed is joined by Chinese companies like Shanghai Vitalgen BioPharma and CorrectSequence Therapeutics in chasing many of the most expensive therapies on the market. For most of the pharmaceutical industry, direct competition is an expected part of the business. That wasn’t necessarily the case with gene therapies. These medicines, which replace defective genes, require intricate scientific design and manufacturing. A 2024 analysis in the Journal of Law and the Biosciences argued that know-how is much tougher to reproduce compared to other parts of drug development. And it was assumed that gene therapies would cure certain rare conditions with a limited market, discouraging competition. But some first-mover therapies had slow uptake, were far from cures or mainly reached wealthy countries . Belief BioMed illustrates how China industrialized gene therapy development, as part of the country’s wider rise in biotech . Trained in China, Xiao’s 35-year career took him from the University of Pittsburgh to the North Carolina company AskBio. He contributed fundamental science behind using AAV vectors to deliver gene therapies. He also navigated scientific challenges and high costs that caused many early US efforts to struggle. Xiao went back to China more than a decade ago upon seeing Chinese patients unable to afford hemophilia B treatments. While patients in wealthy countries get preventative annual therapy covered by insurance, many in China only receive treatment after dangerous bleeding events. Xiao and his colleagues founded Belief BioMed in 2018 to develop a gene therapy, in the hope that a one-time treatment could transform a chronic condition into a curable disease. At the time, the Dutch company uniQure’s hemophilia B therapy was in clinical trials, and would be approved in the US as Hemgenix in 2022 with a $3.5 million list price, part of a wave of multimillion-dollar gene therapies. (The medicine has since been approved in Europe, Canada, Saudi Arabia, and in some Asia-Pacific countries, though not China.) Xiao sought to develop a less costly — and maybe even better — therapy for China and the larger world. Belief’s therapy, like Hemgenix, uses an AAV vector to deliver a working copy of the factor IX gene to cells to produce long-term clotting. Xiao’s team engineered a next-generation capsid that’s designed to improve delivery and reduce immune reactions for greater safety and efficacy. In both early and late-stage studies, a single infusion of Belief’s medicine greatly reduced or eliminated bleeding episodes in the year following treatment, according to findings published last November in Nature Medicine . The clinical results so far appear comparable to Hemgenix, though Belief must dose more commercial patients before making a final comparison. CSL Behring, which commercializes uniQure’s hemophilia B therapy, said in a statement that it’s confident in the value of Hemgenix given its long-term data. It’s working to expand the therapy to countries where it’s not available. Belief’s bigger breakthrough may lie less in science and more in its decision to build its own facility, showing how China can independently develop and commercialize gene therapies. Gene therapy production is notoriously fragile. Scientists grow large batches of specially engineered cells in bioreactors and insert DNA instructions into them. The cells’ own machinery then produces and assembles the viral particles that carry the therapeutic gene. Belief does everything in-house, including producing the genetic material and vectors, to reduce errors that commonly plague the field. In 2022, for instance, US-based Regenxbio publicly said that a third-party manufacturing delay pushed back the start of a study for its Duchenne muscular dystrophy gene therapy. In addition, Belief sought to rethink gene therapy manufacturing processes that had slowly evolved in the US and Europe. The company designed high-yield cells that churn out larger quantities of therapeutic virus, reworked gene insertion steps to reduce waste, and stripped out costly ingredients embedded in earlier-generation processes. The streamlined manufacturing process drove down costs, Xiao said. So did China’s system for quickly testing medicines in humans. The result, he said, is an economic model that makes it possible to pursue gene therapies for conditions that others have deemed too risky or given up on, such as hemophilia A. In February, US-based BioMarin said it would withdraw its hemophilia A therapy from the market after failing to find a buyer . That’s but one example of Western drugmakers pulling back from the field amid challenging economics. Other Chinese companies echo Belief’s philosophy to be better and less expensive. YolTech Therapeutics is in clinical trials with a program that could compete with Casgevy, a $2.2 million gene therapy for sickle cell disease. Rather than removing a patient’s cells and editing them in the lab, as companies in the US have already done, the Shanghai-based biotech edits cells directly in the bone marrow with a simple transfusion. Zi Jun Emma Wang, the chief technology officer and co-founder of YolTech, said it’s too early to talk about pricing but there’s potential to be much lower in cost than Casgevy. “With our cost of goods being an order of magnitude lower than what’s typically the cost for cell therapy, we believe there’s a huge potential,” Wang said. Helen Chen, head of LEK Consulting’s healthcare practice in Shanghai, recalled visiting Chinese companies 15 years ago that had lists of the world’s top-selling drugs in a bid to potentially compete with them. “The difference now is that the competition from China is coming out much faster,” Chen said. “Before it was kind of an amusing lab exercise.” China has the right conditions for gene therapy development, but not necessarily for commercialization, posing business challenges. In China, it can still be difficult to get payer coverage for these treatments . The Chinese government recently expanded insurance coverage for innovative medicines . But gene therapies, even when relatively discounted, remain a tough sell. There’s no alternative but to design a lower-cost gene therapy from the beginning. “We know that in China if you have a $3 million drug, nobody is able to afford it,” said Lijun Wang, the CEO of CoJourney, a company that manufactures gene therapies. US and European challengers, by contrast, aren’t as bound by cost during development. Their payers balk at high gene therapy costs, but more often relent because the medicines replace a lifetime of chronic care. After months of reimbursement struggles that delayed patient dosing, Belief recently secured a breakthrough when a city-level program known as Huiminbao agreed to partly cover the costs for its $350,000 therapy. The company partnered with Takeda China on domestic commercialization. The next test lies abroad. The FDA is skeptical of studies from patients in China. But the company has engaged the FDA with its Chinese clinical and manufacturing data, hoping to avoid or minimize expensive US trials. US approval would grant access to the world’s largest pharmaceutical market, and speed approval elsewhere. Xiao said the therapy’s cost in other markets would be lower than Hemgenix, but added it’s premature to give a concrete price. A discounted gene therapy could be welcome amid slow uptake for hemophilia B gene therapies , particularly in low-income countries that struggle to afford them. “It could have a huge impact,” said hemophilia researcher Glenn Pierce, who has worked with companies like Biogen and Bayer. But, he added, even if it was one-tenth the price, Belief’s therapy could still be too expensive in poorer countries. Already, China’s growing ability to make low-cost gene therapies is driving worldwide patients to Asia, as Endpoints previously reported . Xiao said that compared to when the company was founded, China is bursting with gene therapy manufacturers. Investors are warming up to the space, aiming to be picks and shovels in a potential gene therapy gold rush. “We had no choice but to bite the bullet and build out manufacturing. Now it’s everywhere,” Xiao said.