Molgramostim inhalation(Savara Pharmaceuticals)

-- Priority Review Granted, Prescription Drug User Fee Act (PDUFA) Target Action Date Set for August 22, 2026 -- -- Company Plans to Submit the MOLBREEVI Marketing Authorization Applications (MAAs) for Autoimmune PAP to the European Medicines Agency (EMA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) By the End of Q1 2026 -- -- MOLBREEVI Has the Potential to Be the First and Only Approved Therapy for Autoimmune PAP in the U.S. and Europe -- LANGHORNE, Pa.--(BUSINESS WIRE)-- Savara Inc. (Nasdaq: SVRA) (the Company), a clinical-stage biopharmaceutical company focused on rare respiratory diseases, announced the FDA has filed for review the BLA for MOLBREEVI as a therapy to treat patients with autoimmune PAP. The FDA granted Priority Review with a PDUFA action date of August 22, 2026. “The FDA’s filing of the BLA marks another significant milestone for Savara and the autoimmune PAP community and brings us one step closer to a potential approval in the U.S. in August of this year,” said Matt Pauls, Chair and Chief Executive Officer, Savara. “We believe the considerable body of data in the application demonstrates MOLBREEVI improves pulmonary gas transfer, quality of life, and the clinical symptoms associated with this rare and debilitating lung disease. We are grateful to the FDA for the constructive feedback they have provided throughout development and the review process to date and look forward to continued dialogue with the Agency.” FDA Priority Review designation directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard review applications. 1 In addition to Fast Track and Breakthrough Therapy Designations, MOLBREEVI has been granted Orphan Drug Designation for the treatment of autoimmune PAP by the FDA and the EMA, as well as Innovation Passport (IP) and Promising Innovative Medicine (PIM) designations by the UK’s MHRA. About Autoimmune Pulmonary Alveolar Proteinosis (autoimmune PAP) Autoimmune PAP is a rare lung disease characterized by the abnormal build-up of surfactant in the alveoli. Surfactant consists of proteins and lipids and is an important physiological substance that lines the alveoli to prevent them from collapsing. In a healthy lung, excess surfactant is cleared and digested by immune cells called alveolar macrophages. Alveolar macrophages need to be stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) to function properly in clearing surfactant, but in autoimmune PAP, GM-CSF is neutralized by autoantibodies against GM-CSF, rendering macrophages unable to adequately clear surfactant. As a result, an excess of surfactant accumulates in the alveoli, causing impaired gas transfer, resulting in clinical symptoms of shortness of breath, often with cough and frequent fatigue. Patients may also experience episodes of fever, chest pain, or coughing up blood, especially if secondary lung infection develops. In the long term, the disease can lead to serious complications, including lung fibrosis and the need for a lung transplant. About Savara Savara is a clinical-stage biopharmaceutical company focused on rare respiratory diseases. Our lead program, MOLBREEVI*, is a recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in Phase 3 development for autoimmune pulmonary alveolar proteinosis (autoimmune PAP). MOLBREEVI is delivered via an investigational eFlow ® Nebulizer System (PARI Pharma GmbH) specifically developed for inhalation of a large molecule. Our management team has significant experience in rare respiratory diseases and pulmonary medicine, identifying unmet needs, and effectively advancing product candidates to approval and commercialization. More information can be found at and LinkedIn . *MOLBREEVI is the FDA and EMA conditionally accepted trade name for molgramostim inhalation solution. It is not approved in any indication. MOLBREEVI is a trademark of Savara Inc. Forward-Looking Statements Savara cautions you that statements in this press release that are not a description of historical fact are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words referencing future events or circumstances such as “expect,” “intend,” “plan,” “anticipate,” “believe,” and “will,” among others. Such statements include, but are not limited to, statements related to the timing of the PDUFA action date and potential FDA approval for MOLBREEVI, the anticipated timing of the MAA submissions in Europe and the UK, that MOLBREEVI has the potential to be the first and only approved therapy for autoimmune PAP in the U.S. and Europe, our belief that the considerable body of data in the application demonstrates MOLBREEVI improves pulmonary gas transfer, quality of life, and the clinical symptoms associated with autoimmune PAP, and that we look forward to continued dialogue with the FDA. Savara may not actually achieve any of the matters referred to in such forward-looking statements, and you should not place undue reliance on these forward-looking statements. These forward-looking statements are based upon Savara’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, the risks associated with our ability to successfully develop, obtain regulatory approval for, and commercialize MOLBREEVI for autoimmune PAP; changes to applicable laws and regulations; the ability to project future cash utilization and reserves needed for contingent future liabilities and business operations; the availability of sufficient resources for Savara’s operations and to conduct or continue planned clinical development programs; and the timing and ability of Savara to raise additional capital as needed to fund continued operations. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. For a detailed description of our risks and uncertainties, you are encouraged to review our documents filed with the SEC including our recent filings on Form 8-K, Form 10-K and Form 10-Q. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Savara undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as may be required by law. 1 U.S. FDA website: Contacts Media and Investor Relations Contact Savara Inc. Temre Johnson, Executive Director, Corporate Affairs ir@savarapharma.com

转载来源|药智网2026年FDA的新药审评中，部分候选药物针对治疗空白领域，即在美国层面缺少获批的专门疗法，现实管理主要依赖支持治疗、移植、侵入性操作或毒性负担较高的救治方案。围绕这一类治疗空白，最具代表性的方向包括EBV阳性移植后淋巴增殖性疾病、慢性丁型肝炎、重度白细胞黏附缺陷I型、糖原贮积病Ia型的病因治疗，以及自身免疫性肺泡蛋白沉积症。01EBV阳性移植后淋巴增殖性疾病•药物：Ebvallo•模态：同种异体、EBV特异性T细胞免疫治疗•申报者：PierreFabre•适应症：EBV阳性移植后淋巴增殖性疾病，成人及≥2岁儿童；（按申报口径）既往接受至少一线治疗，其中包括抗CD20相关治疗EBV阳性移植后淋巴增殖性疾病，发生在移植后免疫抑制治疗阶段。其本质为EB病毒驱动的B细胞异常增殖，临床进展可能较快。临床表现缺乏特异性，常见情形包括持续或反复发热、盗汗、体重下降等全身症状；淋巴结肿大或肿块形成；肝脾肿大；移植器官或其他器官的局部症状，例如胃肠道可出现腹痛、腹泻或出血，肺部可出现咳嗽、呼吸困难，中枢神经系统可出现头痛、意识改变或局灶性神经功能缺损；部分患者可出现进行性贫血、血小板减少等血液学异常并伴随乳酸脱氢酶升高。临床处理通常先尝试下调免疫抑制治疗强度，以便让机体免疫功能部分恢复，从而对EB病毒相关异常增殖形成控制。这一步的代价是移植器官排斥反应风险上升，因此需要在抗排斥与控病之间反复权衡。若疾病仍未得到控制，常规药物选择多为利妥昔单抗等抗CD20治疗，用于清除相关B细胞克隆。对一线治疗无反应或进展较快的患者，化疗往往成为后续手段。迄今美国尚无针对该病的病因轴或病理过程的专门获批药物，现有管理更多属于风险权衡下的综合处置与经验性治疗。困难在于移植后患者常伴免疫功能低下、器官功能储备不足和感染风险升高，高强度化疗更容易带来严重毒性与并发症；对于复发或难治人群，缺少可标准化推广的专门治疗方案，治疗结局高度依赖中心经验与个体耐受性。Ebvallo的产品定位直接对准EBV驱动这一病因轴。它属于同种异体EBV特异性T细胞免疫治疗，思路是把可用的EBV定向细胞免疫能力带回患者体内，让免疫系统能更有效地清除EBV相关靶细胞，从而在免疫抑制背景下实现更精准的免疫控制。该产品已经在欧盟获批，用于复发或难治EBV阳性PTLD的成人及2岁以上儿童，这一点等于给出了一条被监管体系认可的临床路径参照。若在美国获得批准，对患者的意义主要体现在两方面：其一，复发难治阶段出现更明确的病因指向治疗选择，有机会降低被动进入高毒性化疗的比例；其二，治疗路径更容易在移植中心标准化，减少完全依赖中心经验的差异。对市场而言，患者基数不大，但高度集中在移植与血液肿瘤中心，支付逻辑往往围绕救命性、稀缺性、住院与并发症成本置换展开，商业化核心将取决于供给可及性、中心覆盖，以及真实世界证据能否支持稳定的临床共识。02慢性丁型肝炎（HDV）•药物：Bulevirtide•模态：多肽•申报者：吉利德•适应症：成人代偿期肝病的慢性丁型肝炎病毒感染慢性丁型肝炎由丁型肝炎病毒引起，该病毒需要乙型肝炎病毒提供包膜蛋白才能完成感染与传播，因此患者通常存在乙型肝炎基础感染。在慢性病毒性肝炎中，乙肝与丁肝共感染导致更快的纤维化进展、更高的肝硬化与肝相关死亡风险，因此被世界卫生组织等机构认定为最严重或最具侵袭性的慢性病毒性肝炎形式。其临床自然史往往更凶险，进展速度更快，较早进入肝硬化阶段的比例更高，随后出现失代偿与肝细胞癌的风险也更高。诊断层面仍存在明显缺口，HDV病毒检测覆盖不足，HDVRNA定量检测的可及性与标准化程度也限制了活动性感染的识别与疗效监测，导致漏诊与延误管理屡屡发生。治疗层面，美国目前可用的药物选择极为有限，临床主要依赖聚乙二醇干扰素作为系统性抗病毒治疗手段，但这一用法属于指南推荐与现实使用层面的选择，其应答率有限，疗效持续性不理想，停药后复发并不少见，耐受性负担使相当一部分患者难以完成足够疗程。对于已进入终末期肝病阶段的患者，肝移植属于少数可能的出路之一，但资源门槛高，等待时间长，围手术期与长期并发症负担也很重。Bulevirtide的机制路径相对清晰。它是脂化多肽抑制剂，靶向肝细胞膜上的NTCP（sodiumtaurocholatecotransportingpolypeptide）受体，阻断HBV与HDV病毒进入肝细胞的入口环节，从而抑制感染过程。它在欧盟以Hepcludex完成了从附条件上市许可到标准上市许可的转换，说明这一机制在真实监管框架内已完成一次关键验证。若在美国获批，对患者的意义是把治疗从疗效有限且耐受性负担重的干扰素体系，推进到更明确的直接抗病毒策略，并为更长期、更可预测的疾病管理打开空间。对市场而言，HDV患者规模不大但疾病负担重，支付讨论常围绕避免肝硬化并发症、延后失代偿、减少移植需求与住院成本展开，真正的放量往往取决于筛查诊断能力提升与专科路径建设，而不只是处方层面的替换。03重度白细胞黏附缺陷I型(LAD-I)•药物：Kresladi•模态：自体慢病毒基因治疗•申报者：RocketPharmaceuticals•适应症：重度白细胞黏附缺陷I型重度白细胞黏附缺陷I型是一种先天性免疫缺陷病，由ITGB2编码的CD18功能缺陷导致白细胞黏附与跨内皮迁移受阻。患儿往往在出生后不久出现反复细菌感染，常见部位包括皮肤、黏膜与呼吸道，可表现为脐炎、肺炎、深部软组织感染等。感染灶常呈炎症反应不足，脓液形成不明显，伤口愈合延迟。新生儿期延迟脐带脱落与持续外周血中性粒细胞显著升高属于具有提示意义的线索。由于感染反复发生且可快速进展，重度表型在缺乏有效根本性干预时具有较高的早期死亡风险。现行管理以抗感染治疗与支持治疗为基础，用于控制急性事件与并发症风险；能够改变疾病自然史的策略主要依赖同种异体造血干细胞移植，其目标是在体内重建具有正常黏附与迁移功能的免疫细胞谱系。未满足需求集中在三方面：移植路径对供者来源与时机高度敏感，存在毒性治疗与移植物抗宿主病风险，且围绕长期免疫重建与感染防控需要高水平中心持续管理。美国监管体系内缺少以LAD-I为适应症、在标签层面获批的专门药物。临床管理更多依赖抗感染与支持治疗来兜底。骨髓移植为唯一可望治愈手段，但存在明显的可及性和风险挑战。Kresladi的模态属于自体慢病毒基因治疗的基因修饰造血干细胞疗法。基本做法是采集患者自身造血干细胞，用慢病毒载体导入功能性基因，再回输到体内，让其重建可表达关键黏附分子功能的免疫细胞谱系，从机制上试图补齐免疫系统的关键功能缺口。Kresladi若获批，患者端的意义非常直接：根治路径从供者依赖的移植，转向自体一次性治疗，供者不确定性显著降低；感染风险与住院负担将在长期维度上降低。市场端则典型符合超罕见病一次性疗法模型：患者人数少，单例价值高，支付可围绕终身成本置换来建立。商业化的关键变量集中在制造周转时间、中心认证覆盖、长期随访体系，以及新生儿或早期确诊后的转诊效率。04糖原贮积病Ia型(GSDIa)•药物：Pariglasgenebrecaparvovec•模态：基因疗法•申报者：Ultragenyx•适应症：糖原贮积病Ia型糖原贮积病Ia型是一种常染色体隐性遗传代谢病，核心缺陷为肝脏等组织中葡萄糖六磷酸酶系统功能不足，导致机体在禁食状态下难以维持血糖输出，糖原和脂质在肝脏、肾脏异常蓄积。典型表现通常在婴儿期开始出现，最突出的问题是反复的禁食性低血糖，可伴抽搐、嗜睡等低血糖相关急症风险；同时常见肝脏明显肿大、腹部膨隆，生长发育受限，常见乳酸升高导致代谢性酸中毒倾向，并可合并高脂血症、高尿酸血症等代谢紊乱。现实管理的核心是严格避免禁食，通过频繁进食和规律补充生淀粉维持血糖稳定，很多患者需要围绕夜间血糖下降而实施持续性补给方案，并长期随访监测。这种管理方式显著延长生存期并降低急性低血糖风险，但并未触及病因轴。长期并发症风险仍然突出，肝脏可出现腺瘤等病变，肾脏也可能逐步出现慢性损害并影响远期结局，疾病负担长期叠加在生活质量、依从性和持续医疗监测之上。当出现严重肝部并发症或肝功能衰竭等情况时，肝移植被作为可选路径之一，并不一定阻止或逆转肾并发症，部分情形需要进一步进入肝肾联合移植策略，但该路径受供体资源、围手术期风险和长期管理要求限制，可及性并不普遍。Pariglasgenebrecaparvovec属于AAV8载体的肝靶向基因治疗，单次静脉给药递送与葡萄糖稳态相关的关键转基因，目标是在肝细胞层面恢复维持血糖稳态所需的关键酶活，从而降低对持续补糖方案的依赖并减少严重低血糖风险。若这一类疗法获批，对患者的意义首先体现在生活与风险结构的改变：补糖依赖度下降、夜间管理压力下降、急性低血糖事件风险下降；随后才是更长期维度的并发症谱可能被改写。对市场而言，这类病因治疗的支付讨论通常围绕长期代偿成本、并发症治疗成本、急性事件风险成本进行置换；真实放量取决于确诊率、专科转诊效率、治疗中心容量，以及长期随访对疗效持续性的信心建设。05自身免疫性肺泡蛋白沉积症（aPAP）•药物：Molbreevi•模态：蛋白质生物药•申报者：Savara•适应症：自身免疫性肺泡蛋白沉积症自身免疫性肺泡蛋白沉积症的病理基础为肺泡巨噬细胞清除表面活性物质的功能受损，肺泡腔内表面活性物质逐步累积，导致气体交换效率下降。临床表现以进行性活动后气促为主，可伴乏力、咳嗽，部分患者出现低氧血症，肺功能检查常体现弥散能力下降，影像学可见与肺泡内容物蓄积一致的改变。长期以来，最常用的干预手段为全肺灌洗，需要在麻醉条件下进行，通过灌洗清除肺泡内沉积物以改善氧合与症状，这一方式能够带来相对快速的缓解，但依赖具备经验的专科中心，侵入性负担较高，且疾病可能复发，部分患者需要重复接受灌洗。由于缺少已获批的专门药物，治疗策略很难形成可长期维持的标准化用药路径，患者管理往往在操作性干预与随访观察之间反复切换，未满足需求集中在可持续、可在常规门诊框架下实施的长期治疗选择。Molbreevi为吸入给药的重组人粒细胞巨噬细胞集落刺激因子，作用机制指向恢复相关信号通路并改善肺泡巨噬细胞功能，开发目标是在病理环节上游降低表面活性物质持续累积的趋势。若获批，患者端的意义是治疗形态的切换：侵入性操作的占比有机会下降，维持治疗更容易在门诊框架内实现，长期随访可以围绕肺功能与生活质量展开。市场端，这属于典型的利基市场，商业化依赖呼吸专科中心覆盖、诊断路径标准化，以及支付方对减少灌洗住院与并发症成本的认可。它有望成为罕见肺病药物化的一次关键推进。06门克斯病从无获批疗法进入标准化治疗•药物：Zycubo•申报者：SentynlTherapeutics•适应症：门克斯病儿科患者•获批时间：2026-01-12门克斯病是一种以铜转运障碍为核心的儿科罕见遗传病，典型起病于婴儿早期，进展较快。临床表现常涉及神经系统与结缔组织发育相关特征，常见情形包括发育迟缓、肌张力低下、喂养困难、反复呕吐或体重增长不良，随后可出现癫痫发作、嗜睡或意识反应减弱等神经系统问题；体征层面具有提示意义的特征之一是毛发异常，表现为稀疏、短而脆、颜色偏浅并呈卷曲或钢丝样改变，同时可见皮肤与结缔组织脆弱、体温偏低等表现，部分患儿可合并血管脆性相关并发症或骨骼改变。由于铜依赖性酶活性不足涉及多条生理通路，疾病可累及多个器官系统，未经有效干预时预后通常较差。Zycubo的获批为门克斯病提供了首个在监管标签下可被标准化执行的治疗选项。对临床而言，最直接的变化是管理路径从经验性处置转向更一致的用药决策，诊断后的治疗启动更容易形成明确的时间窗口与随访框架。对支付体系而言，首个获批治疗通常会带来准入规则的建立与细化，围绕用药指征、给药与监测要求，以及具备管理能力的中心形成更清晰的路径。对患者家庭而言，新增价值主要来自确定性与可及性提升，治疗不再依赖零散经验或个别中心的临时方案，而是进入可被复制的标准化医疗服务体系，从而降低路径不确定性带来的延误与负担。注：本文仅作信息交流之目的，文中观点不代表药智网立场，也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。-END-