Lenadogene nolparvovec

1. FDA批准SpringWorks别构小分子MEK抑制剂 2月12日，SpringWorks Therapeutics宣布，美国FDA已批准MEK抑制剂Gomekli（mirdametinib）上市，用于治疗肿瘤无法完全切除的年龄不低于2岁的1型神经纤维瘤病相关丛状神经纤维瘤（NF1-PN）成人和儿童患者。新闻稿指出，mirdametinib是首个获批可同时用于治疗成人和儿童NF1-PN的药物。Mirdametinib是一种口服别构小分子MEK抑制剂，靶向MEK1和MEK2。FDA的批准是基于2b期临床试验ReNeu的结果，该试验达到了ORR主要终点，成人患者的ORR为41%（24/58），儿童患者的ORR为52%（29/56）。在确认获得缓解的患者中，88%的成人和90%的儿童患者的缓解持续时间至少为12个月，而50%的成人患者和48%的儿童患者的缓解持续时间至少为24个月。 2. 欧盟批准BridgeBio创新疗法，已授权拜耳 2月12日，BridgeBio Pharma宣布，欧盟已经批准Beyonttra（acoramidis）用于治疗伴有心肌病的野生型或变异型转甲状腺素蛋白介导的淀粉样变性（ATTR-CM）成人患者。Acoramidis是一种口服的转甲状腺素蛋白小分子稳定剂，本次批准基于ATTRibute-CM关键研究的结果。该试验成功达成了其主要终点，在第30个月时，与安慰剂相比，acoramidis组的ACM和反复发生的CVH事件减少了42%。Acoramidis起效迅速，在接受治疗后仅3个月时，患者首次发生ACM或CVH事件所需时间就与安慰剂组产生差异。此前于2024年11月，美国FDA已经批准acoramidis上市（商品名：Attruby）用于治疗ATTR-CM患者。而该药在欧洲的独家商业化权利已于2024年3月授予拜耳（Bayer）公司，欧盟的批准将触发7500万美元的里程碑款项。 3. FDA受理再生元CD3/BCMA双抗上市申请 2月12日，再生元（Regeneron）宣布，美国FDA已受理其为CD3/BCMA双特异性抗体疗法linvoseltamab所重新提交的生物制品许可申请（BLA），用于治疗已接受至少四线治疗，或已接受三线治疗且对最后一线治疗耐药的成年复发/难治性多发性骨髓瘤（MM）患者。FDA预计在2025年7月10日前对该申请做出审评决定。Linvoseltamab同时正在接受欧洲药品管理局（EMA）针对相同患者群体的审评。此次BLA重新提交的受理是在再生元解决第三方充填/封装制造问题之后进行的，该问题是FDA在之前该公司BLA提交中所唯一提出的问题。该BLA得到了关键性LINKER-MM1试验数据的支持。 4. Biohaven创新疗法在美国申报上市，获优先审评资格 2月12日，Biohaven宣布，美国FDA已受理该公司在研疗法troriluzole用于治疗成人脊髓小脑共济失调症（SCA）的新药申请（NDA），并授予优先审评资格。根据一项真实世界证据（RWE）研究，经3年治疗后，troriluzole可将SCA患者的病情进展减缓最高达70%。根据新闻稿，若获批准，该药将成为首个获FDA批准用于治疗SCA的药物。这次NDA的递交主要基于BHV4157-206-RWE试验的积极结果。该试验是在与美国FDA讨论后设计的关键性临床研究，旨在评估troriluzole在SCA患者中的疗效，以治疗3年后功能性共济失调评分（f-SARA）变化为衡量指标。该研究利用了3期临床试验数据，并根据FDA的RWE指南，使用来自美国小脑性共济失调临床研究联盟（CRC-SCA）的未治疗SCA患者作为外部对照。多项分析的数据综合显示，在troriluzole治疗组中，SCA患者病情恶化的速度减慢了50%-70%，在3年的研究期间，疾病进展延缓了1.5至2.2年。 5. 诺和诺德「司美格鲁肽」新适应症在中国申报上市 2月12日，CDE官网最新公示，诺和诺德（Novo Nordisk）申报的3.1类新药司美格鲁肽注射液新适应症上市申请获得受理，尚无具体适应症信息披露。根据注册分类及诺和诺德公开资料推测，这可能是司美格鲁肽2.4mg注射剂（商品名为Wegovy），此前已经在中国获批用于长期体重管理。本次该产品在中国申报上市的适应症可能为用于低已确诊心血管疾病的肥胖或超重成人的主要不良心血管事件（MACE）风险。 6. 首个国产FXI抑制剂进入III期阶段，来自恒瑞医药 2月12日，药物临床试验登记与信息公示平台显示，恒瑞医药启动了新型抗凝药SHR-2004的首个III期临床试验。SHR-2004是一种靶向凝血因子XI（FXI）的人源化单克隆抗体，可选择性结合FXI和凝血因子XIa（FXIa），阻碍凝血因子XIIa（FXIIa）对FXI的激活，从而阻断内源性凝血途径的级联反应过程，发挥抗凝作用。目前，全球尚无FXI/FXIa抑制剂上市。本次启动的III期研究是一项多中心、随机、双盲、阳性药物对照临床试验（n=1167），旨在评估接受全膝关节置换术后的成人患者使用SHR-2004（皮下注射，120mg，用药1次或静脉输注1次，90mg，用药1次）或依诺肝素钠（皮下注射，40mg，用药12-14次）或安慰剂预防静脉血栓栓塞症（VTE）的有效性和安全性。 7. GenSight公司发布一次性基因治疗眼科临床结果 2月12日，GenSight Biologics发布了其LUMEVOQ®基因疗法治疗Leber遗传性视神经病变(LHON)的REFLECT III期临床试验五年疗效和安全性的最终结果。结果显示，单次注射LUMEVOQ®后五年，患者视力改善持续存在，且安全性良好。双侧注射相比单侧注射，具有额外获益，尤其在临床相关恢复率方面。LHON 是一种罕见的母系遗传线粒体遗传疾病，会导致视网膜神经节细胞变性，从而导致突然且不可逆转的视力丧失，并可能导致法定失明。LUMEVOQ 是一种针对LHON的基因疗法，通过玻璃体内注射的方式单次给药，旨在为患者提供可持续的功能性视力恢复。 1. 超21亿美元！艾伯维与Xilio合作开发实体瘤TCE 2月12日，艾伯维和 Xilio Therapeutics宣布达成合作和许可选择协议，利用 Xilio 的专有技术开发新型肿瘤激活、基于抗体的免疫疗法，包括掩蔽型T细胞衔接器。Xilio 盘前股票涨幅超170%。根据协议条款，Xilio 将获得总计5200 万美元的预付款，包括1000万美元的股权投资，并有资格获得高达约21亿美元的期权相关费用和里程碑付款以及分级特许权使用费总额。 内容来源于网络，如有侵权，请联系删除。

PARIS, France I February 12, 2025 I GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today reported final efficacy and safety results at the conclusion of the REFLECT Phase III clinical trial with LUMEVOQ ® (GS010; lenadogene nolparvovec). The results show that five years after a one-time administration of the gene therapy, the visual acuity improvement among patients with LHON (Leber Hereditary Optic Neuropathy) was sustained while maintaining a favorable safety profile. Bilateral injections provided an additional effect compared to unilateral treatment, demonstrated in some of the responder rate analyses. “ The latest REFLECT data confirms that the improvement seen with lenadogene nolparvovec is sustained 5 years after treatment has been given, including the additional benefit observed in participants receiving a bilateral intravitreal injection of the gene therapy ,” said Prof. Patrick Yu-Wai-Man , MD, PhD, Professor of Ophthalmology and Honorary Consultant Neuro-ophthalmologist at the University of Cambridge, Moorfields Eye Hospital, and the UCL Institute of Ophthalmology, United Kingdom, and International Principal Investigator of REFLECT. “ Importantly, REFLECT participants receiving a bilateral injection had a comparable safety profile to those treated unilaterally. ” The findings reinforce the results observed at 4 years post-treatment administration, which were reported in March 2024 . Sustained and meaningful efficacy at Year 5 The evolution of the visual acuity over time shows that visual improvement after lenadogene nolparvovec treatment was maintained over 5 years in all subjects. The improvement of placebo eyes highlights the consistent contralateral treatment effect observed in all clinical trials (which was also documented in sham-treated eyes in the REVERSE 1 and RESCUE 2 trials). (See Graph 1.) Because of the severity of the acute phase in LHON, vision could still deteriorate to a low point or nadir in the initial period of the trial. This characteristic of the disease makes the observed nadir (i.e., the worst BCVA recorded from baseline to Year 5) a better reference point to assess the effect of the therapy than baseline vision, which varies greatly depending on the disease stage at the time of enrollment in the study. Relative to the observed nadirs, average visual acuity for all LUMEVOQ-treated eyes increased beyond the +15-letter threshold (-0.3 LogMAR change) that conventionally defines clinically meaningful improvement. (See Table 1.) Responder analyses reinforce the finding of improved outcomes for patients, for whom natural history typically results in greatly impaired vision with a very low likelihood of spontaneous recovery 3 . Five years after injection, patients who were bilaterally treated experienced a higher rate of clinically relevant recovery* from their nadir, compared to patients who had unilateral treatment (75% vs. 60%). 79% of bilaterally treated patients were able to read letters on a screen (on-chart vision), compared to 72% of patients treated in only one eye. Table 1: Change in Best-Corrected Visual Acuity (BCVA) versus Nadir 5 Years after Injection Database lock: Dec 31, 2024. Subjects bilaterally treated: 1st affected eyes: n=48; 2 nd affected eyes: n=48; subjects unilaterally treated: 1 st affected eyes: n=50; 2 nd affected eyes: n=50. p<0.0001 for all eye groups using linear mixed model. Favorable safety profile The favorable safety profile of LUMEVOQ ® continued to be confirmed, with the safety profile of the drug being demonstrated as comparable in bilaterally and unilaterally treated subjects. There was no study discontinuation related to systemic or ocular adverse events, and there were no serious ocular adverse events. The main ocular adverse event was intraocular inflammation, which was mostly mild and responsive to conventional treatment. REFLECT was a randomized, double-masked, placebo-controlled Phase III trial involving 98 subjects with vision loss due to LHON caused by a mutated ND4 mitochondrial gene; enrolled ND4 subjects had vision loss up to one year from onset. All subjects received an intravitreal injection (IVT) of lenadogene nolparvovec in their first affected eye. The second affected eye was randomized to either a second IVT of LUMEVOQ ® or a placebo IVT, which was administered on the same day or the following day. 48 subjects were randomized to LUMEVOQ ® bilateral treatment, and 50 to lenadogene nolparvovec unilateral treatment (first-affected eye treated with LUMEVOQ ® , second-affected eye treated with placebo). REFLECT patients were followed up to 5 years post-injection. * “Clinically Relevant Recovery”, or CRR, refers to an improvement in Best-Corrected Visual Acuity (BCVA) that satisfies one of two conditions: (1) A 10-letter (≥0.2 LogMAR) improvement for an on-chart starting visual acuity. (2) Improvement from “off-chart” to “on-chart” (≤1.6 LogMAR). References: About GenSight Biologics GenSight Biologics S.A. is a clinical-stage biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics’ pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics’ lead product candidate, GS010, is in Phase III trials in Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease that leads to irreversible blindness in teens and young adults. Using its gene therapy-based approach, GenSight Biologics’ product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery. About Leber Hereditary Optic Neuropathy (LHON) Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1 st eye, with the 2 nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of subjects have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. About LUMEVOQ ® (GS010; lenadogene nolparvovec) LUMEVOQ ® (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. “LUMEVOQ” was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018. LUMEVOQ® (GS010; lenadogene nolparvovec) has not been registered in any country at this stage. About REFLECT REFLECT was a multi-center, randomized, double-masked, placebo-controlled study to evaluate the safety and efficacy of bilateral injections of GS010 in subjects with LHON due to the NADH dehydrogenase 4 ( ND4 ) mutation. In the active arm, GS010 was administered as a single intravitreal injection in each eye of each subject. In the placebo arm, GS010 was administered as a single intravitreal injection to the first affected eye, while the fellow eye received a placebo injection. The primary endpoint for the REFLECT trial was the BCVA reported in LogMAR at 1.5 years (78 weeks) post-treatment in the second‑affected/not‑yet‑affected eye. The change from baseline in second‑affected/not‑yet‑affected eyes receiving GS010 and placebo was the primary response of interest. The secondary efficacy endpoints included: change from baseline in BCVA reported in LogMAR at 2, 3, 4 and 5 years post-treatment in the second‑affected/not‑yet‑affected eye compared to both placebo and the first‑affected eye receiving GS010, change from baseline in OCT and contrast sensitivity as well as quality of life scales. The trial was conducted in multiple centers across Europe/UK (1 each in France, Spain, Italy and the UK), the US (6 centers) and Taiwan (1 center). The trial planned to enroll 90 subjects with vision loss up to 1 year in duration; 98 subjects were successfully screened and treated. The first subject was treated in March 2018 and the last one in July 2019. Long-term follow-up of the last patient was completed on July 23, 2024. SOURCE: GenSight Biologics