Methylenedioxymetamfetamine

同写意20周年大会：中国医药创新未来之路！“意”同创新，穿越周期，赢取未来。7月中旬，苏州金鸡湖畔，让我们与“新药写意人”一起为中国医药创新“同写意”！ 进入7月，下半年FDA药物审批紧罗密布。 其中，有五款药物值得额外关注，审批结果甚至会影响某类适应症的市场格局。 例如，去年最大的两起生物技术公司收购案都围绕着一种新型精神分裂症治疗药物展开。到9月底，其中第一种药物将获得FDA的批准，这一决定将凸显人们对精神药物的关注。 其他新型精神治疗药物也正在接受测试，包括亚甲二氧甲基苯丙胺（MDMA，俗称“摇头丸”）和裸盖菇素等迷幻药。 FDA在这方面需要做出艰难的决定，因为其顾问小组最近批评了使用MDMA辅助心理疗法治疗创伤后应激障碍。  伴随着矛盾和期待，更多药物的审批正在路上。 1 精神类药物“两开花” 几十年来，一种新型的抗精神病药物可能首次进入市场。 该药物名为KarXT，由Karuna Therapeutics公司开发，已经取得了多项成功。 两项大型安慰剂对照试验发现，精神分裂症患者服用该药物后，在衡量其症状严重程度的评分系统中，症状“减轻程度”显著增加。这种药物见效迅速，两项研究的主要治疗期都持续了5周。 虽然KarXT确实有副作用，但对比传统的抗精神病药物，该药物不会引发体重过度增加、烦躁不安或运动问题。KarXT和Cerevel Therapeutics的一款竞争药物通过刺激一种控制乙酰胆碱释放的蛋白质起作用，乙酰胆碱是一种对大脑功能很重要的化学物质。 医生们表示，KarXT对精神分裂症患者来说是一极具“吸引力”的选择。 华尔街分析师预计，KarXT将在9月26日前获得批准。一些人甚至认为，该药物在巅峰时期的年销售额将超过100亿美元。对于BMS而言，这将是一笔不俗的收入，该公司最近以140亿美元收购了Karuna。 换句话说，药物获批与否决定着BMS的投资决策是否正确。 无独有偶，Lykos Therapeutics也在聚焦精神类疾病的治疗，该公司主要利用“摇头丸”辅助治疗精神疾病。 但是，Lykos目前的进展似乎并不乐观，主要原因是缺少支持性数据。 到目前为止，该公司已经进行了两项后期研究，评估MDMA作为中度至重度创伤后应激障碍患者谈话疗法的辅助手段。结果显示，在18周和三个疗程中，与仅接受谈话疗法的患者相比，接受MDMA治疗的患者在“创伤后应激障碍症状严重程度的量表”上显著减轻。 该公司认为，这些试验提供了足够的证据，可以让MDMA成为FDA批准的首个迷幻剂辅助疗法。 然而，在最近一次机构顾问会议之后，这种希望似乎逐渐渺茫。 顾问小组一致投票反对该药物，理由是担心其安全性以及Lykos进行试验的方式。道德违规指控（包括性行为不端和数据隐瞒）也对Lykos的申请产生了影响。 虽然FDA没有义务遵循顾问的建议，但通常情况下，顾问小组的决策通常会产生连锁反应。这意味着会议结束后批准的可能性可能会降低。最终决策将在8月11日之前公布。 2 大厂的“高光”时刻？ 相比于可能开创先河的神经类药物，MCN们也在等待着FDA的审判。 在花费超过200亿美元购买抗癌药物后，吉利德于今年2月收购了CymaBay，重回肝病领域。 这笔43亿美元的收购，让吉利德拥有了一种治疗原发性胆汁性胆管炎的实验性药物，原发性胆汁性胆管炎是一种由肝脏中胆汁酸毒性积聚引起的慢性疾病。 改药物名为“seladelpar”，FDA预计在8月14日之前做出审批。一旦获批，吉利德的肝病领域的地位将更上一层楼。该公司估计，美国约有13万人患有原发性胆汁性胆管炎。 美国还批准了另外两种用于治疗原发性胆汁性胆管炎的药物：Intercept Pharmaceuticals的Ocaliva和最近获批的益普生的 Iqirvo。这两种药物都伴随着安全警告，这意味着如果FDA批准了seladelpar，那么该药物的将发挥重要作用。 之前，由于担心存在安全问题，seladelpar在另一种肝病MASH中的试验被叫停，但后续试验显示安全问题并不存在。 吉利德强调了seladelpar在抑制与PBC相关瘙痒方面的有效性，并预计该药物如果获得批准，将为今年的销售做出“适度”贡献。 到今年年底，武田将停止生产美国唯一一种治疗罕见内分泌疾病甲状旁腺功能减退症的处方药。在这一情况下，如果FDA批准丹麦生物技术公司Ascendis Pharma开发的治法TransCon PTH，未来将会提供一种崭新的选择。 Ascendis是一种替代形式的甲状旁腺激素，美国约有7.7万名患有甲状旁腺功能低下症的人缺乏这种激素，导致钙含量低和其他健康问题。该药物基于TransCon技术，Ascendis使用这种技术来微调药物的特性以便于输送。 2022年的III期研究结果显示，接受TransCon PTH治疗的试验参与者中约79%的钙水平正常，大多数人之后不需要补充维生素。 Ascendis已在欧洲和英国获得批准，但该公司在美国面临着更艰难的道路——FDA因制造问题于2023年拒绝了TransCon PTH，5月，还将裁决推迟了三个月。 最终决定可能在8月14日之前做出，一旦获批，将为该公司带来数十亿美元的收入。还会让Ascendis领先几家潜在竞争对手，其中包括阿斯利康。 3 关乎命运的决策 2017年以来，FDA已批准了6款CAR-T细胞疗法，如果FDA决定批准物技术公司Adaptimmune的实验药物，另一种细胞药物可能会在本季度上市。 Adaptimmune成立于200年，专注于TCR细胞疗法，该疗法与CAR-T疗法类似，但依赖于能够识别细胞内靶标的蛋白质受体。这种能力可以使TCR细胞疗法能够更好地攻击CAR-T难以治疗的实体肿瘤。 但Adaptimmune一直难以证明自己的价值。近年来，该公司失去了葛兰素史克和罗氏这两家“大腿”，裁员并重组了产品线。如今，股价每股约1美元，价值仅为2015年首次公开募股价格的一小部分。 一旦FDA批准公司的afami-cel（一种治疗罕见软组织癌滑膜肉瘤的 TCR 疗法），它的命运将会被改写。 值得注意的是，华尔街分析师认为FDA将在8月4日的最后期限前批准afami-cel。 不过，Adaptimmune仍面临afami-cel市场潜力的质疑。瑞穗证券的分析师已将峰值年销售额预测下调至1.74亿美元，因为预计“接受度”比之前预想低。虽然获得批准可能会给Adaptimmune带来机会，但市场表现同样无法忽略。 从上述分析可得，下半年FDA的决策将会在神经疾病、罕见病、肝病一级细胞疗法领域带来影响。 参考文献： https://www.biopharmadive.com/news/5-fda-approval-decisions-watch-third-quarter-2024/720492/ 更多优质内容，欢迎关注↓↓↓

Two of last years largest biotechnology company acquisitions centered on a new type of treatment for schizophrenia. By the end of September, the first of those therapies could win Food and Drug Administration approval, a decision that would highlight the new attention being paid to psychiatric drugs.Other novel psychiatric treatments are working their way through testing, too, including psychedelics like MDMA and psilocybin. The FDA has a tough decision to make on that front, as a panel of its advisers recently panned the use of MDMA-assisted psychotherapy for post-traumatic stress disorder.Elsewhere, Gilead Sciences might get an OK for a drug it recently acquired via its deal for CymaBay Therapeutics and a new kind of cell therapy could reach market. Here are five FDA decisions to watch in the third quarter:Bristol Myers Kar-XT for schizophreniaFor the first time in decades, a truly new form of antipsychotic could be coming to market.The drug, known as KarXT and developed by Karuna Therapeutics, already has multiple wins under its belt. Two large, placebo-controlled trials found schizophrenia patients given it had significantly greater reductions on a scoring system that measures the severity of their symptoms. The drug also seems to work fast, with the main treatment period of both studies lasting five weeks.While KarXT does have side effects, it doesnt appear to cause the excessive weight gain, restlessness or movement issues that older antipsychotics often elicit. Unlike those medications, KarXT and a rival medicine from Cerevel Therapeutics work by stimulating a kind of protein that controls the release of acetylcholine, a chemical important to brain function.Doctors foresee KarXT being an attractive option for schizophrenia patients, who often switch medications because of side effects or because the drugs arent controlling their disease well enough. Still, there are concerns that insurance providers will resist covering a drug like KarXT, since many generic and inexpensive antipsychotics are already available.On Wall Street, analysts expect KarXT will secure approval by the FDAs Sept. 26 decision deadline. Some even believe the drug will generate more than $10 billion in yearly sales at its peak. Whether that comes to fruition is in the hands of Bristol Myers Squibb, which recently bought Karuna for $14 billion.I think youre gonna get a massive bolus of early adopters, said Paul Matteis, an analyst at the investment firm Stifel, in an interview late last year. And I think Bristol [Myers] just has to not mess it up. Jacob BellLykos MDMA-based therapy for PTSDLykos Therapeutics believes it can build a business around MDMA also known as the party drug ecstasy. To do that, the company, formerly named MAPS Public Benefit Corp., identified a novel version of the drug and set up a series of patents to protect it.But Lykos needed supportive data as well. So far, it has run two late-stage studies evaluating MDMA as an aid to talk therapy for people with moderate-to-severe post-traumatic stress disorder. Results showed that, over the course of 18 weeks and three treatment sessions, patients who received MDMA had a significantly greater reduction on a scale measuring the severity of PTSD symptoms, compared to those who just got talk therapy.The company thought the trials provided enough evidence to make MDMA the first psychedelic-assisted therapy approved by the FDA. Those hopes appear slimmer, however, following a recent meeting of agency advisers.The panel of advisers voted almost unanimously against the drug, citing concerns about its safety and the ways Lykos conducted the trials. Allegations of ethics violations, including sexual misconduct and data suppression, also weighed on Lykos application.The FDA isnt required to follow the recommendations of its advisers. But it typically does, meaning the odds of approval are likely lower following the meeting. The agency is expected to make a decision by Aug. 11. Jacob BellGileads seladelpar for primary biliary cholangitisAfter spending more than $20 billion on cancer drug deals, Gilead got back to its liver disease roots with its February acquisition of CymaBay. The $4.3 billion buyout gave Gilead an experimental treatment for primary biliary cholangitis, a chronic condition caused by the toxic build-up of bile acid in the liver.Called seladelpar, the drug would expand Gileads liver disease portfolio beyond hepatitis if approved by the FDAs target decision date of Aug. 14. The company estimates about 130,000 people in the U.S. have primary biliary cholangitis, or PBC, and expects that its salesforce would cover about 80% of the prescribers who treat the condition.Two other drugs are approved in the U.S. for PBC: Intercept Pharmaceuticals Ocaliva and Ipsens more recently cleared Iqirvo. Both carry notable safety warnings, meaning that the labeling of seladelpar, if OKd by the FDA, could play an important role in how well its adopted. Testing of seladelpar in another liver condition called MASH was previously halted on safety worries that later proved unfounded.Gilead has highlighted seladelpars effectiveness in curbing the itching associated with PBC and expects the drug, if approved, to contribute modestly to sales this year. Ned PagliaruloAscendis TransCon PTH for hypoparathyroidismBy the end of the year, Takeda will stop making the only prescription medication available in the U.S. for a rare endocrine condition called hypoparathyroidism, ending a drug launch marred by slow sales and production issues. But a new option could emerge this quarter if the FDA approves TransCon PTH, a therapy developed by Danish biotech Ascendis Pharma.Ascendis drug provides a replacement form of parathyroid hormone, which is lacking in the estimated 77,000 people in the U.S. with hypoparathyroidism, causing low calcium levels and other health problems. Its based on a technology, TransCon, that Ascendis uses to fine-tune the properties of a medicine for delivery.Phase 3 study results in 2022 showed about 79% of trial participants treated with TransCon PTH had normal calcium levels. Most didnt need vitamin supplements afterwards. Ascendis has since won approvals in Europe and the U.K. But the company has faced a tougher road in the U.S. The FDA rejected TransCon PTH in 2023 due to manufacturing concerns and, in May, delayed its verdict by three months as the responses Ascendis provided constituted a major amendment to its application.A decision could finally come by Aug. 14 and, if positive, unlock what some analysts forecast as a multibillion-dollar revenue opportunity. An approval would also keep Ascendis ahead of several would-be competitors, among them AstraZeneca, which recently acquired a startup with a drug in late-stage testing. Ben FidlerAdaptimmunes afami-cel for synovial sarcomaSince 2017, the FDA has approved six CAR-T cell therapies and, earlier this year, cleared for the first time a different kind of immune cell treatment. Another type of cellular medicine could reach the market this quarter if the agency OKs an experimental drug from biotech Adaptimmune.Formed in 2008, Adaptimmune is focused on TCR cell therapies, which are similar to CAR-T treatments but rely on protein receptors that can recognize intracellular targets. That capability could make TCR cell therapies better able to attack the solid tumors CAR-T struggle to treat.But Adaptimmune has had difficulty proving their worth. In recent years, the company lost both GSK and Roche as partners, laid off staff and restructured its pipeline. At about $1 apiece, shares are worth a fraction of their initial public offering price in 2015.The companys fortunes could shift if the FDA approves afami-cel, a TCR therapy for a rare soft tissue cancer called synovial sarcoma. Wall Street analysts are optimistic the FDA will clear afami-cel by an Aug. 4 deadline, as the agency hasnt called on outside advisors to scrutinize the data or, executives have said, communicated issues with Adaptimunes study results. The company has financial room to work with, too, having cut deals with Galapagos and Hercules Capital in May.Still, Adaptimmune faces questions on afami-cels market potential. Analysts at Mizuho Securities have lowered peak annual sales projections to $174 million amid expectations of more conservative uptake than they previously thought. While an approval may bring validation to Adaptimmune, strong commercial performance will be important to support a positive view of the companys prospects, wrote Leerink Partners Thomas Chang in a recent client note. Ben Fidler '