Sepiapterin

「  本文共：21条资讯，阅读时长约：25分钟 」细胞与基因治疗突破1.全球首创6小时极速CAR-T制备技术临床疗效显著。上海细胞治疗集团开发的JL-闪CAR-T™平台，将传统9-11天的制备周期缩短至6小时，大幅降低生产成本。其三靶点CAR-T产品BZE2204在难治性淋巴瘤IIT临床试验中实现100%完全缓解率（CR），且剂量仅为市售产品的1/40，体内扩增能力达常规产品的30-200倍，无三级以上毒副作用。2.UCLA创新“串联T细胞疗法”攻克免疫细胞耗竭难题。通过输注基因改造的造血干细胞（HSCs），在体内持续产生抗癌T细胞，解决现有疗法中T细胞易耗竭的问题。I期临床试验显示，新生成的T细胞无耗竭迹象，并内置“自杀基因”sr39TK作为安全开关，可通过PET追踪或紧急清除。3.上海医药CAR-T疗法B019获批系统性红斑狼疮临床试验。全球首次将靶向CD19/CD22的CAR-T疗法扩展至自身免疫疾病领域，为传统治疗无效的难治性红斑狼疮患者提供新选择，此前该疗法已用于血液肿瘤治疗。抗体药物与ADC进展1.迈威生物靶向CDH17 ADC药物7MW4911获中美IND受理。该药物采用新型毒素MF-6载荷，可克服多药耐药性，在结直肠癌、胃癌及胰腺癌的临床前模型中均显示深度抑瘤效果。其高膜渗透性设计增强旁观者杀伤效应，且对CDH17低表达肿瘤仍有效。2.礼新医药PD-1/VEGF双抗LM-299完成技术转移，获默沙东3亿美元付款。全球首款PD-1/VEGF双抗MK-2010（原LM-299）完成技术转移，默沙东支付3亿美元里程碑款。该药拟用于实体瘤治疗，目前处于全球多中心临床阶段。3.康宁杰瑞HER2双抗JSKN003获FDA批准开展卵巢癌II期临床。针对铂耐药卵巢癌，该双抗已获中美孤儿药认定，临床前数据显示其对低HER2表达肿瘤仍具显著活性。代谢疾病与内分泌创新1.博瑞医药与华润三九合作推进GLP-1/GIP双激动剂BGM0504。双方就治疗2型糖尿病和肥胖症的BGM0504注射液签署研发协议，该双靶点药物已进入III期临床。华润三九将利用其商业化网络加速产品上市，应对中国1.48亿糖尿病患者的未满足需求。2.石药集团口服GLP-1药物SYH2086授权Madrigal，交易额超20亿美元。石药将SYH2086的全球权益（除中国外）授权给美国Madrigal，获1.2亿美元预付款及最高19.55亿美元里程碑付款，创中国代谢类药物海外授权金额新高。3.礼来替尔泊肽新增胰岛素联用适应症在华获批。GLP-1R/GIPR双靶点药物替尔泊肽（穆峰达®）获NMPA批准联合胰岛素治疗成人2型糖尿病，此前已获批单药减重适应症。罕见病与特殊疗法1.FDA批准苯丙酮尿症新药Sephience，84%患者指标达标。PTC Therapeutics的口服药物Sephience（sepiapterin）获FDA批准，用于1个月以上苯丙酮尿症患者。III期试验显示其降低血液苯丙氨酸水平63%，84%患者达到治疗目标（<360µmol/L），22%恢复至正常水平。2.赛诺菲获普乐司兰钠大中华区权益，瞄准罕见血脂疾病。赛诺菲从维亚臻获得RNAi药物普乐司兰钠的开发权，该药通过抑制载脂蛋白C-III治疗家族性乳糜微粒血症综合征（FCS）。中国III期临床已达终点，并于2025年1月提交NDA。3.乐普医疗重组A型肉毒毒素获批临床。采用基因工程合成技术，相比传统提取工艺纯度更高、生物风险更低，有望打破进口垄断。适应症涵盖医美与医疗领域。中国创新药国际化1.恒瑞医药与GSK达成120亿美元战略合作。恒瑞将呼吸、自免及肿瘤领域创新药HRS-9821的海外权益（除大中华区外）授权给GSK，首付款5亿美元。协议还包括至多11个项目的全球选择权，总潜在金额约120亿美元。2.华领医药华堂宁®全面接管商业化，上半年溢利预达11.84亿元。终止与拜耳的推广协议后，华领医药自主销售葡萄糖激酶激活剂华堂宁®（多格列艾汀）。因收回未摊销合约负债12.44亿元，2025年上半年溢利预增11.84亿元。国内创新药试验数据1. 肿瘤免疫治疗康方生物 AK112（PD-1/VEGF双抗）最新进展：启动第11项Ⅲ期临床（HARMONi-7），针对PD-L1 TPS≥50%初治肺癌，与帕博利珠单抗头对头比较OS；差异化优势：单药布局覆盖PD-L1全表达人群，此前单药一线治疗NSCLC已获批，瑞银预测全球销售峰值146亿美元。君实生物 特瑞普利单抗（PD-1单抗）黑色素瘤一线数据：中位OS达15.1个月（vs 化疗9.4个月，HR=0.68），ORR 11%且缓解持续13.8个月；适应症扩展：成为首个获批晚期黑色素瘤一线免疫治疗的国产PD-1，国内累计获批12项适应症。2. 细胞治疗与自身免疫病上海医药 B019（CD19/CD22 CAR-T）适应症拓展：获批系统性红斑狼疮（SLE）临床试验，全球首个从血液瘤跨入自免疾病的CAR-T疗法。3. 代谢疾病礼来 替尔泊肽（GLP-1R/GIPR双激）中国新批适应症：获批联合胰岛素治疗2型糖尿病，完善代谢领域全域布局。 重大交易进展1.博瑞医药 & 华润三九：GLP-1/GIP双激动剂BGM0504靶点：GLP-1R/GIPR双靶点开发阶段：Ⅲ期临床进行中（2型糖尿病/肥胖症）差异化优势疗效潜力：双靶点协同作用有望超越单靶点GLP-1药物减重与降糖效果。商业化保障：华润三九支付2.82亿元研发里程碑款，整合渠道加速上市。2.荣昌生物 & Vor Bio：泰它西普（RC18）全球授权靶点：BLyS/APRIL双靶点（全球首创双靶向机制）开发阶段中国：已获批系统性红斑狼疮（SLE）、重症肌无力（MG）、类风湿关节炎（RA）。全球：MG适应症Ⅲ期临床中，干燥综合征（pSS）、IgA肾病获FDA批准直接开展Ⅲ期。差异化优势重症肌无力数据：24周治疗，98.1%患者MG-ADL评分改善≥3分，87%患者QMG评分改善≥5分，显著优于现有FcRn/C5抑制剂。专利保护：中国专利期延长至2032年（+5年独占期）。交易亮点：首付款4500万美元+股权+最高41亿美元里程碑款，荣昌持股Vor Bio约23%，深度绑定长期收益。3. 恒瑞医药 & GSK：HRS-9821海外授权靶点：未公开（呼吸、自免及肿瘤领域多靶点管线）开发阶段：临床前至早期临床（具体适应症未披露）差异化优势交易结构：首付款5亿美元+120亿美元潜在总额，涵盖至多11个项目全球选择权。战略意义：恒瑞持股合作平台Hercules 19.9%，避免权益被“转售稀释”（对比此前TSLP抗体被转卖GSK事件）。4. 石药集团 & Madrigal：口服GLP-1药物SYH2086靶点：GLP-1R小分子激动剂（口服剂型突破）开发阶段：Ⅱ期临床完成，即将进入Ⅲ期差异化优势便捷性：口服给药规避注射剂患者依从性难题。交易价值：首付款1.2亿美元+19.55亿美元里程碑款，创中国代谢药出海金额纪录。股市资讯8月1日A股医药公司涨幅TOP 3百济神州（688235.SH） +18.25%主要影响因素：PD-1单抗替雷利珠单抗获FDA批准用于胃癌一线治疗，成为首个在美获批该适应症的国产PD-1。康希诺（688185.SH） +14.36%主要影响因素：与Gavi签署15亿美元新冠疫苗预购协议，覆盖中低收入国家2026年需求。华东医药（000963.SZ） +11.78%主要影响因素：GLP-1受体激动剂利拉鲁肽类似药获批上市，定价较原研低40%。8月1日A股医药公司跌幅TOP 3ST康美（600518.SH） -5.00%主要影响因素：因持续经营能力存疑被实施退市风险警示。华大基因（300676.SZ） -4.35%主要影响因素：新冠检测业务继续萎缩，上半年净利润同比下滑52%。以岭药业（002603.SZ） -3.12%主要影响因素：连花清瘟海外销售不及预期，遭多家投行下调目标价。8月1日港股医药公司涨幅TOP 3信达生物（01801.HK） +22.17%主要影响因素：与赛诺菲达成50亿美元双抗ADC合作，首付款3亿美元创国内纪录。药明生物（02269.HK） +16.89%主要影响因素：宣布新建全球最大生物药CDMO基地，总投资100亿元。金斯瑞生物（01548.HK） +13.45%主要影响因素：CAR-T疗法获欧盟批准用于多发性骨髓瘤二线治疗。8月1日港股医药公司跌幅TOP 3中国生物制药（01177.HK） -7.23%主要影响因素：核心产品安罗替尼遭医保局重点监控，预计年销售额减少30%。石药集团（01093.HK） -5.67%主要影响因素：阿尔茨海默病药物III期临床数据不及预期，终止研发。三生制药（01530.HK） -4.89%主要影响因素：大股东折价12%减持8000万股，套现约6亿港元。评审动态8月1日新药临床试验申请IND7月新药上市申请NDA（申请类型为新药或进口，不包括仿制&已有国家标准）END

iStock, Grandbrothers The FDA greenlit multiple new drugs this month and issued some notable label expansions including for Eli Lilly’s Kisunla. Meanwhile, the regulator turned away a cell therapy for Duchenne muscular dystrophy and a gene therapy for the rare disease Sanfilippo syndrome. Amid an exodus of employees —not to mention the official start of Health Secretary Robert F. Kennedy Jr.’s overhaul of the agency—the FDA issued several key verdicts this month. Among the standout decisions are a Duchenne muscular dystrophy rejection, a dosing modification for an anti-amyloid Alzheimer’s therapy and an approval for the first-ever on-demand oral therapy for hereditary angioedema. Read below for more. Regeneron’s Bispecific Notches Accelerated Approval for Multiple Myeloma Drug: Lynozyfic Decision: New drug approved Date: July 2 To kick off the month, the FDA handed Regeneron a modest win in multiple myeloma with its approval of linvoseltamab, a bispecific antibody targeting both BCMA and CD3 proteins, for patients with relapsed or refractory multiple myeloma., The regulator’s greenlight for the drug, to be marketed as Lynozyfic, was supported by data from the Phase I/II LINKER-MM1 study that demonstrated a 70% objective response rate, including a 45% complete response rate or better. In a prepared statement alongside its announcement of the approval, Regeneron CEO George Yancopoulos said that with this efficacy profile, “Lynozyfic is poised to potentially become a new standard of care for multiple myeloma.” In a July 2 note, analysts at BMO Capital Markets called the approval a “small win” for Regeneron, with Lynozyfic being a “minor contributor to the company’s broader product portfolio.” BMO models around $600 million in potential revenues for Lynozyfic. The peak forecast for Lynozyfic is modest in part because it trails Johnson & Johnson’s Tecvayli , which was approved in 2022, giving it a three-year head start. Regeneron has emphasized the greater convenience of its product, however. According to the pharma, Lynozyfic is the first and so far only bispecific with this mode of action that can be dosed every two weeks, with the possibility of extending to every four weeks if a patient achieves very good partial response or better. Despite Interference, KalVista Gets Delayed Nod for Only On-Demand HAE Pill Drug: Ekterly Decision: New drug approved Date: July 7 TK weeks after the PDUFA deadline passed, the FDA signed off on KalVista’s sebetralstat, to be marketed under the brand name Ekterly, as the first and only oral on-demand therapy for acute hereditary angioedema (HAE) attacks. The approval comes after the regulator in June had to push back its decision date for the drug, pointing to “heavy workload and limited resources,” KalVista said at the time. There had also been some internal disagreement over the verdict, with Commissioner Marty Makary reportedly trying to get the application denied, according to Endpoints News , which cited anonymous sources at the agency. Makary relented after senior staff raised potential legal issues about his interference. The Department of Health and Human Services has denied these claims, with a spokesperson telling Endpoints that they are “totally false and untrue.” Results of the Phase III KONFIDENT study supported Ekterly’s approval. Results presented in February 2024 showed that both 300-mg and 600-mg doses of Ekterly achieved symptom relief significantly more rapidly , with a median of 1.61 hours and 1.79 hours, respectively, versus 6.72 hours for the placebo group. The open-label KONFIDENT-S trial bolstered these findings, demonstrating that in the real-world setting, Ekterly can help patients address HAE attacks within a median of 10 minutes of onset. KONFIDENT is the largest HAE program ever conducted, KalVista claims. PTC Wins Phenylketonuria Nod for Sephience Drug: Sephience Decision: New drug approved Date: July 28 On July 28, the FDA signed off on PTC Therapeutics’ sepiapterin, which will now be marketed under the brand name Sephience, for the treatment of adults and children with phenylketonuria (PKU). The approval, the biotech noted, grants Sephience a broad label and allows its use for addressing hyperphenylalaninemia in patients 1 month of age and older. This broad labeling, CEO Matthew Klein said in a prepared statement, points to “the potential of Sephience to meet the significant unmet need of PKU patients.” Data from the Phase III APHENITY trial supported Sephience’s approval. PKU is caused by a deficiency of phenylalanine hydroxylase, leading to the accumulation of phenylalanine in patients’ tissues and body fluids. Results posted in October 2024 showed Sephience could cut phenylalanine by 63% in treated patients. This effect was stronger in study participants with classic PKU, with phenylalanine reduction reaching 69%. Almost 85% of patients achieved phenylalanine levels lower than 360 µmol/L, in line with treatment guidelines. Lilly, Moderna, Bayer, GSK Win Expanded Labels for Key Assets July 9: Eli Lilly’s Kisunla The FDA signed off on a new dosing regimen for Eli Lilly’s Alzheimer’s disease therapy Kisunla. This modified schedule involves a more gradual titration of the drug, which according to the pharma lowers the risk of amyloid-related imaging abnormalities indicative of fluid accumulation (ARIA-E). Data from the TRAILBLAZER-ALZ 6 study supported this change, showing that at week 24, ARIA-E was detected in 14% of patients treated with the gradual titration of Kisunla, as opposed to 24% of those on the initially approved dosing schedule. By week 52, ARIA-E was reported in 16% and 25% of the respective groups. July 10: Moderna’s Spikevax Moderna likewise won a major label expansion this month, with the FDA granting full approval for its COVID-19 vaccine Spikevax in children 6 months through 11 years of age who are at high risk of getting infected. Spikevax was previously available for this age group only under an Emergency Use Authorization. Spikevax’s full approval comes after two key approvals for Moderna’s mRNA vaccine pipeline last month. The first was for its next-generation COVID-19 shot mNEXSPIKE , which is now cleared for older adults 65 and above, as well as people 12 through 64 years of age who have at least one underlying risk factor. The second was for its respiratory syncytial virus shot, mResvia , which secured broader coverage to include at-risk adults aged 18 through 59 years. July 14: Bayer’s Kerendia Also securing a key expansion this month is Bayer’s Kerendia, which the FDA gave a new indication : to reduce the risk of cardiovascular death, hospitalization for heart failure and urgent visits for heart failure in adult heart failure patients with left ventricular ejection fraction of at least 40%. In the Phase III FINEARTS-HF study, Kerendia elicited a significant 16% reduction in the trial’s primary endpoint, a composite of worsening heart failure events and cardiovascular death. Kerendia likewise resulted in an 18% drop in worsening heart failure events. Kerendia was first approved in July 2021 , indicated to lower the risk of sustained kidney function decline, end-stage kidney disease, cardiovascular death, heart failure hospitalization and non-fatal myocardial infarction in patients with chronic kidney disease associated with type 2 diabetes. July 17: GSK’s Shingrix Arguably one of the biggest label expansions this month is for GSK’s shingles shot Shingrix, for which the FDA greenlit a prefilled syringe formulation . This new version, according to the pharma’s press release, simplifies the immunization process for healthcare professionals by removing the need to reconstitute separate vials of the vaccine. Approved in October 2017 , Shingrix is a recombinant herpes zoster vaccine indicated for the prevention of shingles in seniors 50 years and older. The vaccine has also since been expanded to cover at-risk adults 18 years and above. Shingrix is one of GSK’s best-performing assets and has already comfortably passed the blockbuster mark. Last year, the product brought in nearly $4.5 billion in sales. Capricor Suffers 40% Hit After FDA Thumbs Down DMD Cell Therapy Drug: Deramiocel Decision: New cell therapy rejected Date: July 11 Aside from important approvals, the FDA also issued critical rejections in July, often with harsh consequences on a company’s stock. One clear example of this is Capricor Therapeutics, which was proposing the investigational cell therapy deramiocel to treat cardiomyopathy in patients with Duchenne muscular dystrophy. The FDA handed Capricor a complete response letter (CRL) on July 11, sending the biotech’s stock freefalling 40% that day. Capricor has yet to recover. As of writing, the company has dipped some 6.3% further. The FDA’s rejection was based on Capricor’s data package for deramiocel, which the regulator said fell short of the “statutory requirement for substantial evidence of effectiveness.” The CRL also cited certain deficiencies regarding deramiocel’s chemistry, manufacturing, and controls. Capricor claimed at the time of the rejection that it had already addressed these concerns, but that the FDA was not able to review these submissions “due to the timing of the CRL issuance.” The rejection came as a surprise to Capricor, CEO Linda Marbán said in a prepared statement at the time. “We have followed their guidance throughout the process,” she said, noting that prior to the CRL the review of deramiocel “had advanced without major issues, including a pre-licensure inspection and completion of the mid-cycle review.” As in the case of KalVista’s Ekterly, deramiocel has been the subject of some internal disagreement at the FDA. Nicole Verdun, the former top regulator of cell and gene therapies at the FDA’s Center for Biologics Evaluation and Research (CBER), had previously scheduled an advisory committee meeting for the application, which new CBER leader Vinay Prasad later cancelled. Verdun was subsequently pushed out of the agency. Ultragenyx Misses Out on Rare Genetic Disease Approval Drug: UX111 Decision: New gene therapy rejected Date: July 11 Ultragenyx reported on July 11 that the FDA had declined to approve UX111, its gene therapy for Sanfilippo syndrome type A, a rare and genetic metabolic disorder that manifests as a broad range of symptoms, including developmental delays and progressive intellectual disability. According to the biotech, the rejection was not linked to its data package for UX111. “The FDA has acknowledged that the neurodevelopmental outcome data provided to date are robust and the biomarker data provide additional supportive evidence,” a statement from Ultragenyx read. Instead, the CRL cited manufacturing issues that were “not directly related to the quality of the product,” Ultragenyx said. “The company believes that these observations are readily addressable.” Ultragenyx added that the company will work to resolve these issues “in the next few months,” building up to a resubmission for UX111. The rare disease biotech expects to undergo another six-month review period after refiling for approval. The rejection capped off a difficult week for Ultragenyx, which on July 9 reported that its Phase II/III osteogenesis imperfecta study for the anti-sclerostin antibody UX143 would be moving to its final analysis. William Blair analysts at the time took this to mean that the trial failed to meet an efficacy threshold that would have otherwise warranted its early termination. As of writing, Ultragenyx’s shares have slid 33% since the osteogenesis imperfect announcement. Roche’s Earlier-Stage Push for Columvi Falls Short Drug: UX111 Decision: Label expansion rejected Date: July 21 The FDA has rejected Roche and subsidiary Genentech’s proposal to use the bispecific antibody Columvi as part of a second-line treatment regimen in patients with diffuse large B cell lymphoma. The Complete Response Letter cited insufficient evidence to support the use of Columvi in this indication in the U.S. patient population. Roche used data from the Phase III STARGLO study to support its application. Results showed that patients treated with the Columvi combo saw a 41% drop in the risk of death compared with those who received rituximab, gemcitabine and oxaliplatin. The Columvi-based regimen likewise hit secondary endpoints, including progression-free survival. Despite these results, the FDA’s Oncologic Drugs Advisory Committee (ODAC) in May voted 8–1 against Columvi’s expansion, raising concerns about the applicability of the drug’s efficacy data in the U.S. In STARGLO’s intention-to-treat population, only 25 of more than 270 participants were from North America. Columvi remains approved as a third-line treatment option for diffuse large B cell lymphoma (DLBCL) under the FDA’s accelerated pathway program. Roche and Genentech are also studying Columvi in the Phase III SKYGLO study , which combines the bispecific with Polivy, Rituxan, cyclophosphamide, doxorubicin and prednisone for the treatment of patients with large B cell lymphoma. The companies are in discussions with the FDA to use SKYGLO as the new postmarketing requirement to convert the third-line DLBCL indication to a full approval, as per their July 21 announcement.