Lovotibeglogene autotemcel

Investment in developers of cell and gene therapies has nosedived this year, a sharp drop-off that investors and analysts say reflect manufacturing and drug delivery challenges at a time when biotechnology companies with clear development paths are increasingly favored.So far this year, makers of cell and gene therapies have raised half of a billion dollars across 16 venture rounds, according to data from DealForma published by Nature. Even annualized, those numbers are well below the $8.2 billion in funding brought in by the 121 deals DealForma counted during the sectors peak in 2021. Last year, cell and gene therapy developers raised $3.5 billion across 65 deals.Were largely seeing investments shifting to things that are de-risked, said Jon Norris, a managing director at HSBC Innovation Banking. Cell and gene therapy is becoming an area we know better, because there are products that have advanced through development, but it still doesn't compare to the number of approvals and drugs commercially available in small molecules or biologics.Overall, biotech venture investment has ticked higher over the first half of 2024, according to a mid-year report from HSBC Innovation Banking. Yet, regardless of technology or research field, biotechs still face a challenging financing environment.Developers of cell and gene therapies face additional hurdles, however, given that the kind of capital required to advance these therapies is different from small molecule drugs or biologics, said Peter Sletteland, a managing director for Silicon Valley Banks life science and healthcare practice. You typically need to spend significant investment in manufacturing.Still, he added, cell and gene therapies garner a lot of attention because of the promise of what they could do.Six CAR-T cell therapies have been approved by U.S. regulators to treat cancer and, in some indications, their benefits can be dramatic. But hopes of replicating that success with so-called allogeneic therapies, which use donor cells rather than individual patients, has been harder to come by than initially envisioned by investors. And uptake of some of the approved CAR-T therapies has been slow, especially as companies work through manufacturing bottlenecks.In gene therapy, sickle cell treatments Casgevy and Lyfgenia secured milestone approvals from U.S. regulators late last year. But only a few dozen patients have begun the process to receive treatment, reflecting the long manufacturing and infusion times needed for each.Adoption has also been slow for the hemophilia gene therapies Hemgenix and Roctavian, while other gene therapy developers like Pfizer have hit clinical setbacks.Patient perception of gene therapy is a crucial barometer. “The therapy has to be worth it, but the question is, are there treatment alternatives?“ said Chris Bardon, co-managing partner at MPM BioImpact.For diseases that have limited treatment options, it may be easy for a patient to consider an intensive cell or gene therapy treatment, which can require arduous chemotherapy preconditioning. But such treatments may by less appealing to people with conditions that are manageable with approved medicines, such as is the case in hemophilia.“It has been a challenge for investors,“ Bardon said.The challenge of developing and selling cell and gene therapies, though, isnt enough to deter investors and drugmakers entirely.In cell therapy, for instance, theres buzz around the potential to target hard-to-treat autoimmune disorders, said Bruce Levine, a cell and gene therapy pioneer at the University of Pennsylvania who co-founded Tmunity Therapeutics and Capstan Therapeutics with colleague Carl June.That's the nature of a therapy that, currently, through the cost of goods and services, is expensive to manufacture, but delivers long-term, durable benefit in patients who have failed all other available therapies, Levine said. '

近日，蓝鸟生物（bluebird bio）公布了该公司的2024第二季度财报，其中较为注意的焦点是蓝鸟的负债。蓝鸟再度与此前就贷款1.75亿美元给该公司的Hercules Capital签订了约5000万美元的贷款协定。 这令人不得不担心蓝鸟是否在未来有能力偿还债务？ 有先例在前，上市了首款前列腺癌症疫苗的Provenge的Dendreon就是因为欠下约6.5亿美元债务无力偿还而最终破产的。尽管目前该公司已经有三款高价基因治疗产品迈入市场，但是商业化的进程却是乏善可陈，Q2净收入不进反退。 不尽如人意的商业化 2023年全年Bluebird上市产品ZYNTEGLO和SKYSONA加起来才卖出去了26款，虽然说今年Q1 Lyfgenia、Skysona和Zynteglo三款产品卖出去15名患者，已经达到了去年的一半以上，理论上算上20%的药品折扣，总销售额能达到3千多万美元，确实也拿到了1860万美元的净收入，似乎有逆转势头的趋势，但这似乎只是一个季度的个例。 今年Q2 Lyfgenia、Skysona和Zynteglo三款产品不进反退，加起来只卖出去12名患者，净收入为1610万美元，今年半年共卖出去27款。 从患者人数来看，β地贫疗法Zynteglo无疑担起了大梁，但是接受其他两款疗法治疗的患者仍然乏善可陈。 导致销售额不进反退的原因可能是CMS的报销问题，虽然说Bluebird确实在大力推动CMS在各州的报销，但因为各州所接受的承保范围不一样，实际覆盖或许有待提高。还有一部分患者居住并不承保上述药物的州。 报销和激励问题 一般来说CMS报销的比例是65%，但是今年4月时CMS答应将Lyfgenia的报销比例增加至75%。这一报销比例将于美国政府的2025财年生效，并在2-3年内的创新技术周期结束时结束。 因此Lyfgenia真正出现增量的时间可能是2025年。 真正值得担忧的可能是生育激励，因为使用大梁Zynteglo和Lyfgenia等疗法，在过程中采用了化疗调理，有非常高的不孕不育风险。需要收集和冷冻患者的生殖组织，如卵子、胚胎和精子，以备将来使用。 如果是老年患者或许还没有这样的顾虑，但是这两类患者都并非老年发病，基本都是婴幼儿发病，例如β地贫，发病年龄愈早，病情愈重。因此都是需要提前进行生育保障措施，而这显然又需要钱，这就有赖于生育激励。 然而，对于基因疗法中采用生育激励的举措，美国卫生与人类服务部（HHS）显然并不认可。 首先，它可以被视为“对患者的报酬”，这反过来可以激励患者选择该公司的疗法，而不是潜在的竞争对手。根据HHS下辖监管机构OIG的说法： 生育援助的目的是消除经济障碍，这样符合条件的病人就可以购买蓝鸟的疗法。医生这个过程还能拿到回扣，这就可能会让医生优先开出蓝鸟的处方，造成不当竞争。 总结 总的来说，2024年下旬到2025年可能是证明蓝鸟商业模式是否可行的时间段，如果这个时间点Bluebird无法拿出成绩，未来就会面临资不抵债的结果。