A Prospective Observational Study to Assess the Long-term Safety and Immunogenicity of Olipudase Alfa Therapy During Routine Clinical Care in Pediatric Patients Less Than 2 Years of Age With Acid Sphingomyelinase Deficiency

US, multicenter, cohort, open label observational study with primary data collection. Ancillary protocol-specified procedures to address the study objectives (eg, assessment of ADA) may be considered outside the standard of care for acid sphingomyelinase deficiency (ASMD), but the study methodology remains non-interventional, as the additional collection of data from participants will not dictate treatment. The total overall study duration will be 5 years. The follow-up period will be a minimum of 1 year to a maximum of 3 years. The enrollment period will be up to 4 years, to allow a minimum of 1 year of follow-up for the last participant enrolled.

开始日期2024-04-16

申办/合作机构

Sanofi

NCT05359276 / RecruitingN/A

Acid Sphingomyelinase Deficiency (ASMD): Data Analysis of Adult and Pediatric Patients on Early Access to Olipudase Alfa in France

Primary Objective:
To describe the lung, spleen and liver outcomes of olipudase alfa
Secondary Objectives:
To describe the patient's characteristics
To describe conditions of olipudase alfa use
To describe safety data related to the use of olipudase alfa
To describe complementary effectiveness outcomes parameters

开始日期2022-06-10

申办/合作机构

Sanofi

JPRN-jRCT2031210279 / Completed临床2/3期

An open label interventional single-patient study to evaluate the safety of olipudase alfa enzyme replacement therapy for the patient in Japan with acid sphingomyelinase deficiency (ASMD) who has completed Study DFI12712

开始日期2021-09-15

申办/合作机构-

100 项与 Olipudase alfa 相关的临床结果

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100 项与 Olipudase alfa 相关的转化医学

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100 项与 Olipudase alfa 相关的专利（医药）

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项与 Olipudase alfa 相关的文献（医药）

Orphanet journal of rare diseases

Real-life impacts of olipudase alfa: The experience of patients and families taking an enzyme replacement therapy for acid sphingomyelinase deficiency

Article

作者: Wiseman, Samantha ; Donnelly, Conan ; Pountney, Jackson ; Crowe, Joslyn ; Raebel, Eva M ; Mathieson, Toni ; Hopkin, Justin

Abstract:

Background:

Acid Sphingomyelinase Deficiency (ASMD) is an ultra-rare autosomal recessive lysosomal storage disorder characterized by intracellular lipid accumulation resulting from reduced function of acid sphingomyelinase. Olipudase alfa, an enzyme replacement therapy, was recently approved in several countries for the treatment of the non-neurologic manifestations of ASMD. Studies demonstrate improvement in organomegaly, pulmonary function and lipid profiles with olipudase alfa, yet little is known about its impact on quality of life (QoL) for patients and caregivers. The purpose of this study is to better understand the real-life impact of ASMD on patients and caregivers and assess how olipudase alfa impacts QoL for pediatric patients and their caregivers.

Methods:

Caregivers of pediatric patients (≤ 18 years of age) with a confirmed diagnosis of ASMD that received olipudase alfa for at least 12 months were recruited in early 2022 through national patient organizations to participate in a global online questionnaire followed by semi-structured interviews. Ten caregivers of patients with ASMD who utilized olipudase alfa as an experimental therapy for pediatric patients participated in the study. Quantitative analysis of the results was undertaken, and qualitative data was analyzed using an inductive thematic approach.

Results:

Ten eligible participants completed questionnaires, and 8 of the 10 went on to participate in structured interviews. Symptom burden of ASMD and impact on symptomatology and quality of life after olipudase alfa use are reported here. Five themes emerged from analysis: (1) ASMD is a systemic disease with a wide array of manifestations that significantly impact QoL; (2) Olipudase alfa was associated with improvements in all non-neurologic manifestations of ASMD; (3) Participants perceived the risk associated with olipudase alfa to be low and the benefits to greatly outweigh any risk or burden; (4) Participants reported an unmet need to treat the neurologic manifestations of the disease despite the benefits of olipudase alfa in the management of non-neurological symptoms; (5) Participants felt all patients with ASMD need access to olipudase alfa based on the life-changing experience they perceived.

Conclusions:

These findings highlight the sustained positive impact olipudase alfa had in many domains that are deemed important to patients and families living with ASMD and outline the extensive unmet need for patients and families living with ASMD.

2023-07-01·Journal of molecular medicine (Berlin, Germany)

Acid sphingomyelinase expression is associated with survival in resectable pancreatic ductal adenocarcinoma.

Article

作者: Turner, Kevin M ; Patel, Sameer H ; Gulbins, Erich ; Wilson, Gregory C ; Xu, Kui ; Carpinteiro, Alexander ; Szabo, Ildiko ; Wang, Jiang ; Becker, Katrin Anne ; Ahmad, Syed A

Pancreatic adenocarcinoma (PDAC) is one of the most common cancers worldwide. Unfortunately, the prognosis of PDAC is rather poor, and for instance, in the USA, over 47,000 people die because of pancreatic cancer annually. Here, we demonstrate that high expression of acid sphingomyelinase in PDAC strongly correlates with long-term survival of patients, as revealed by the analysis of two independent data sources. The positive effects of acid sphingomyelinase expression on long-term survival of PDAC patients were independent of patient demographics as well as tumor grade, lymph node involvement, perineural invasion, tumor stage, lymphovascular invasion, and adjuvant therapy. We also demonstrate that genetic deficiency or pharmacological inhibition of the acid sphingomyelinase promotes tumor growth in an orthotopic mouse model of PDAC. This is mirrored by a poorer pathologic response, as defined by the College of American Pathologists (CAP) score for pancreatic cancer, to neoadjuvant therapy of patients co-treated with functional inhibitors of the acid sphingomyelinase, in particular tricyclic antidepressants and selective serotonin reuptake inhibitors, in a retrospective analysis. Our data indicate expression of the acid sphingomyelinase in PDAC as a prognostic marker for tumor progression. They further suggest that the use of functional inhibitors of the acid sphingomyelinase, at least of tricyclic antidepressants and selective serotonin reuptake inhibitors in patients with PDAC, is contra-indicated. Finally, our data also suggest a potential novel treatment of PDAC patients with recombinant acid sphingomyelinase. KEY MESSAGES: Pancreatic ductal adenocarcinoma (PDAC) is a common tumor with poor prognosis. Expression of acid sphingomyelinase (ASM) determines outcome of PDAC. Genetic deficiency or pharmacologic inhibition of ASM promotes tumor growth in a mouse model. Inhibition of ASM during neoadjuvant treatment for PDAC correlates with worse pathology. ASM expression is a prognostic marker and potential target in PDAC.

2023-05-01·Advances in therapy

Healthcare Service Use Patterns Among Patients with Acid Sphingomyelinase Deficiency Type B: A Retrospective US Claims Analysis

Article

作者: Fournier, Marie ; Ganz, Michael L ; Petruski-Ivleva, Natalia ; Pulikottil-Jacob, Ruth

INTRODUCTION:

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease. Patients with ASMD type B experience multiple morbidities, potentially leading to early mortality. Before the 2022 approval of olipudase alfa for non-neuronopathic ASMD manifestations, only symptom management was offered. Data on healthcare services used by patients with ASMD type B are limited. This analysis used medical claims data to evaluate real-world healthcare service use by patients with ASMD type B in the United States of America (USA).

METHODS:

The IQVIA Open Claims patient-level database (2010-2019) was cross-examined. Two patient cohorts were identified: the primary analysis cohort, which included patients with at least two claims associated with ASMD type B (ICD-10 code E75.241) and more total claims with ASMD type B than any other ASMD types, and the sensitivity analysis cohort, which included patients with a high probability of having ASMD type B identified using a validated machine-learning algorithm. Claims for ASMD-associated healthcare services were recorded, including outpatient visits, emergency department (ED) visits, and inpatient hospitalizations.

RESULTS:

The primary analysis cohort included 47 patients; a further 59 patients made up the sensitivity analysis cohort. Patient characteristics and healthcare service use were similar in both cohorts and were consistent with established characteristics of ASMD type B. Overall, 70% of the primary analysis cohort from this study were aged < 18 years, and the liver, spleen, and lungs were the most frequently affected organs. Cognitive, developmental, and/or emotional problems and respiratory/lung disorders caused most outpatient visits; respiratory/lung disorders accounted for most ED visits and hospitalizations.

CONCLUSION:

This retrospective analysis of medical claims data identified patients with ASMD type B who had characteristics typical of this condition. A machine-learning algorithm detected further cases with a high probability of having ASMD type B. High use of ASMD-related healthcare services and medications was observed in both cohorts.

项与 Olipudase alfa 相关的新闻（医药）

2024-05-17

·CPHI制药在线

频繁出手，赛诺菲努力打造罕见病帝国

关注并星标CPHI制药在线近日，赛诺菲动作频频，先是与生物制药公司Fulcrum Therapeutics（简称Fulcrum）达成合作，获得其在研新药Losmapimod在美国以外所有地区的独家开发和商业化权益；两天后，又宣布将加大对在法国的三个生产基地的投资，总额超10亿欧元。一系列动作背后，折射出了赛诺菲面对王牌产品即将迎来专利悬崖的焦虑和打造罕见病帝国的决心。潜在超10亿美元付款，引进一款罕见病产品近日，赛诺菲发布了2024年第一季度财报，公司销售收入为104.64亿欧元（约112.24亿美元），同比强劲增长6.7%。在制药部门，其核心大单品靶向IL-4R单抗药物——度普利尤单抗（Dupixent，商品名：达必妥）一季度销售额为28.35亿欧元，贡献了制药部门绝大部分业绩。然而Dupixent专利将于2027年到期，为了应对专利悬崖，赛诺菲开始不断向外拓展合作。5月13日，赛诺菲与Fulcrum达成独家合作协议，赛诺菲将获得Fulcrum的Losmapimod（洛吡莫德）的开发和商业化权益。Fulcrum将获得8000万美元首付款，以及潜在高达9.75亿美元的监管和销售里程碑付款。Losmapimod是一款选择性p38α/β丝裂原活化蛋白激酶（MAPK）抑制剂，旨在通过阻断p38α和p38β蛋白来降低双同源盒转录因子4（DUX4）基因的活性。Losmapimod最初由GSK研发，2019年，Fulcrum从GSK手中收购了Losmapimod的所有权益。目前，Losmapimod主要被用来开发治疗面肩肱型肌营养不良症（FSHD）。FSHD是一种罕见且严重的肌肉萎缩症，其特征是骨骼肌脂肪浸润导致肌肉萎缩，主要累及面部、肩胛骨等，逐渐导致患者日常活动能力下降、独立性丧失等，目前尚无批准的治疗方法。在FSHD中，约95%的患者是由于4 号染色体变异，造成DUX4基因异常表达所引起。因此，Losmapimod在FSHD领域具有很大的潜力。在治疗FSHD的IIb期临床试验中，评估了Losmapimod治疗FSHD的安全性和有效性。试验共招募80名患有1型 FSHD且DUX4表达抑制丧失的患者。结果显示，与安慰剂组相比，Losmapimod组FSHD患者的DUX4驱动的基因表达水平呈现出下降趋势但并无统计学意义。但是Losmapimod组患者的肌肉脂肪浸润情况、肌肉萎缩情况和生活质量均有所改善。因此，Fulcrum还是决定将Losmapimod推进至III期阶段。22亿美元，收购AATD领域在研治疗药物除了收购Fulcrum外，今年1月，赛诺菲和Inhibrx达成合作协议，将收购与INBRX-101相关的所有资产和负债，该笔交易总价值为22亿美元。INBRX-101是一款拟用于治疗 α-1抗胰蛋白酶缺乏症（AATD）的重组人AAT-Fc融合蛋白候选治疗物，目前正在注册试验中。AATD是一种遗传性孤儿病，其特征是A1AT蛋白水平不足，这会导致患者的肺组织及其功能丧失，进而导致患者的预期寿命缩短。INBRX-101有望使AATD患者在减少用药次数（每月一次）的情况下实现血清α-1抗胰蛋白酶水平的正常化。目前正在开展 II 期临床试验，以进一步评估治疗AATD患者的潜力。以临床价值为导向，赛诺菲旨在打造罕见病帝国赛诺菲在罕见病领域的布局可以追溯到2011年。当年，赛诺菲以201亿美元收购Genzyme（健赞），入局罕见病领域。此后，赛诺菲不断通过并购丰富罕见病管线，包括通过收购Ablynx和Bioverativ，分别从两家公司获得了纳米抗体新药Cablivi和Eloctate、Alprolix等多款血友病新药等。目前，赛诺菲在罕见病领域共布局了11条在研管线，其中6个候选产品处于III期临床。2023年，罕见病领域产品成为公司业绩主要来源之一，其中Nexviazyme（庞贝病）、Enjaymo（冷凝集素病）、Xenpozyme（酸性鞘磷脂酶缺乏症）3款罕见病产品表现亮眼。为了满足新药产能需求，赛诺菲近日表示，将在法国的三个生产基地Vitry、Le Trait、Lyon Gerland投资超10亿欧元，以增加新药和疫苗产能。其中赛诺菲将10 亿欧元投向Vitry工厂，以将其单克隆抗体产能提高一倍，包括治疗慢性阻塞性肺病（COPD）、多发性硬化症等疾病的药物。近几年，赛诺菲正在进行重组优化，如剥离免疫肿瘤产品开发公司Amunix Pharmaceuticals、关闭NK细胞疗法开发公司Kiadis Pharma、削减与IGM Biosciences的合作，放弃原计划在肿瘤学领域的三个靶点等，以筹集资金，来加速布局罕见病等领域。随着候选药物研究的快速推进与产能不断扩张，赛诺菲距离打造罕见病帝国的梦想，正在越来越近。参考来源：1. Press release: Sanofi to acquire Inhibrx, adding potential best-in-class rare disease asset for Alpha-1 Antitrypsin Deficiency to pipeline.2. Maze Therapeutics Announces Exclusive Worldwide License Agreement with Sanofi for MZE001, an Oral Sub.3. strate Reduction Therapy for the Treatment of Pompe Disease；MazeFDA Approves First Treatment for Acid Sphingomyelinase Deficiency, a Rare Genetic Disease. Retrieved August 31, 2022 from https://www.sanofi.com/en/media-room/press-releases/2022/2022-06-28-05-30-00-2469974.【智药研习社近期线下课程预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

引进/卖出并购临床3期财报

2024-03-20

·FiercePharma

#FierceMadness is back: Get voting in the 2024 drug name tournament

This year we’re taking the branded drug names that were officially approved by the FDA in 2022 and 2023 - now it's your turn to vote for your winner. LAUNCHED: Wednesday, March 20, 7:00 a.m. ET It’s March, so it’s time for some #FierceMadness. Last year, we channeled the NCAA tournament for the best pharma ad campaigns, but, this year, we’re looking for the best of the best in drug names. Here’s how it works. We’ve chosen 64 of the most distinctive drug names to come out of the FDA’s 2022 and 2023 crop of new approvals. Whittling down to 64 from the 92 drug names available was our staff challenge, but now it’s up to you, readers, to deliberate and vote down to the final winner. Remember, this isn’t about the drugs themselves—neither how well they may work (or not) nor any controversies in how they may have been approved. Our goal is to assess their marketing suitability, considering how well they perform in their respective field and against competitors. Ready to play? Check out the bracket here (PDF) and see the full Madness 64 list below. Then vote is via our poll here. You can vote from now until Friday, March 22, at 6 p.m. ET. Check back here Monday, March 25, for your results, and the chance to vote in the next round. After that, we’ll be back with a new round each Wednesday and Monday through Monday, April 8, when you can vote for your championship winner. Any remote robo-voting will be noted, and those votes will be discarded. Please play fair. Don’t forget to tell us why you picked what you picked in the voting poll comments section—and what you think each drug name really sounds like. We’ll include the funniest and most out-of-the-box comments in our recaps every round, so make 'em good! New this year: Our sister publication Fierce Biotech is also running its own Madness tournament for the best of the best in biotech company names. Check out and vote in its championship here. Good luck, and happy Madness! #FierceMadness 2024: The full bracket of 64 Jesduvroq vs. Lamzede Jesduvroq Maker: GSK Indication: Anemia due to chronic kidney disease Sounds like: When you hit your finger with a hammer, but it’s in front of your children so you’re trying not to swear Lamzede Maker: Chiesi Indication: Non-central nervous system manifestations of alpha-mannosidosis Sounds like: A vegan meal Pluvicto vs. Lunsumio Pluvicto Maker: Novartis Indication: Prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer following other therapies Sounds like: A new planet Lunsumio Maker: Roche Indication: Relapsed or refractory follicular lymphoma, a type of non-Hodgkin lymphoma Sounds like: A Japanese wrestler Briumvi vs. Camzyos Briumvi Maker: TG Therapeutics Indication: Relapsing forms of multiple sclerosis Sounds like: A sixth-generation cheese Camzyos Maker: Bristol Myers Squibb Indication: Obstructive hypertrophic cardiomyopathy Sounds like: A Spanish holiday resort Voquezna vs. Mounjaro Voquezna Maker: Phathom Pharmaceuticals Indication: Helicobacter pylori infection Sounds like: A sports drink with a kick Mounjaro Maker: Eli Lilly Indication: Lowering blood sugar levels in Type 2 diabetes Sounds like: A legendary medieval sword fighter Vtama vs. Amvuttra Vtama Maker: Dermavant Indication: Plaque psoriasis Sounds like: A mouthful Amvuttra Maker: Alnylam Indication: Polyneuropathy of hereditary transthyretin-mediated amyloidosis Sounds like: A pope’s gift Xenpozyme vs. Daxxify Xenpozyme Maker: Sanofi Indication: Acid sphingomyelinase deficiency Sounds like: An alien protein Daxxify Maker: Revance Indication: The treatment of cervical dystonia and for the temporary improvement of frown lines Sounds like: A ray gun to make you sassy Fruzaqla vs. Sotyktu Fruzaqla Maker: Takeda Pharmaceuticals Indication: Refractory, metastatic colorectal cancer Sounds like: A European swear word Sotyktu Maker: Bristol Myers Squibb Indication: Moderate to severe plaque psoriasis Sounds like: Gesundheit! Terlivaz vs. Imjudo Terlivaz Maker: Mallinckrodt Pharmaceuticals Indication: Improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function Sounds like: A Hungarian dance Imjudo Maker: AstraZeneca Indication: Unresectable hepatocellular carcinoma Sounds like: A self-confident martial artist Elahere vs. Vabysmo Elahere Maker: ImmunoGen Indication: Recurrent ovarian cancer that is resistant to platinum therapy Sounds like: An inebriated attempt at Hawaiian Vabysmo Maker: Roche Indication: Neovascular (wet) aged-related macular degeneration and diabetic macular edema Sounds like: A new way of saying fantastic Pyrukynd vs. Rystiggo Pyrukynd Maker: Agios Indication: Hemolytic anemia in pyruvate kinase deficiency Sounds like: A drunk Scrabble game Rystiggo Maker: UCB Indication: Generalized myasthenia gravis in adults who are anti-acetylcholine receptor- or anti-muscle-specific tyrosine kinase antibody-positive Sounds like: An Italian village Beyfortus vs. Xdemvy Beyfortus Maker: AstraZeneca Indication: To prevent respiratory syncytial virus lower respiratory tract disease Sounds like: A medieval stronghold Xdemvy Maker: Tarsus Pharmaceuticals Indication: Demodex blepharitis Sounds like: Elon Musk’s drunk attempt at renaming his business Tzield vs. Rezlidhia Tzield Maker: Provention Bio Indication: Delay the onset of stage 3 Type 1 diabetes Sounds like: An electronic barrier Rezlidhia Maker: Rigel Pharmaceuticals Indication: Relapsed or refractory acute myeloid leukemia with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation Sounds like: A new Disney princess Krazati vs. Leqembi Krazati Maker: Mirati Therapeutics Indication: KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer in adults who have received at least one prior systemic therapy Sounds like: A crazy party Leqembi Maker: Eisai Indication: Alzheimer’s disease Sounds like: An inspirational French aphorism Cibinqo vs. Brenzavvy Cibinqo Maker: Pfizer Indication: Refractory, moderate to severe atopic dermatitis Sounds like: A game of cheeky bingo Brenzavvy Maker: TheracosBio Indication: Glycemic control in adults with Type 2 diabetes mellitus as an adjunct to diet and exercise Sounds like: Heard in a copy of "Pirates of the Caribbean" Jaypirca vs. Skyclarys Jaypirca Maker: Eli Lilly Indication: Relapsed or refractory mantle cell lymphoma in adults who have had at least two lines of systemic therapy, including a BTK inhibitor Sounds like: A strong coffee Skyclarys Maker: Biogen Indication: Friedreich’s ataxia Sounds like: A high-rise building Zavzpret vs. Paxlovid Zavzpret Maker: Pfizer Indication: Migraine treatment Sounds like: A Turkish fast-food restaurant Paxlovid Maker: Pfizer Indication: Mild to moderate COVID-19 in adults at high risk for progression to severe COVID-19 Sounds like: A bizarre Pac-Man sequel Inpefa vs. Columvi Inpefa Maker: Lexicon Pharmaceuticals Indication: Heart failure Sounds like: An anti-fascist offshoot group Columvi Maker: Roche Indication: Diffuse large B-cell lymphoma, not otherwise specified, or large B-cell lymphoma arising from follicular lymphoma after two or more lines of systemic therapy Sounds like: An ancient Roman detective Daybue vs. Zynyz Daybue Maker: Acadia Indication: Rett syndrome Sounds like: How my five-year-old insists debut is spelled Zynyz Maker: Incyte Indication: Metastatic or recurrent locally advanced Merkel cell carcinoma Sounds like: Drug naming companies may be running out of ideas Rezzayo vs. Qalsody Rezzayo Maker: Melinta Therapeutics Indication: Candidemia and invasive candidiasis Sounds like: A phrase used when you’ve had a great nap in the day Qalsody Maker: Biogen Indication: Amyotrophic lateral sclerosis in adults who have a SOD1 gene mutation Sounds like: From the makers of “Better Call Saul” comes “better Qalsody” Elfabrio vs. Veozah Elfabrio Maker: Chiesi Indication: Fabry disease Sounds like: The lost Spanish Mario brother Veozah Maker: Astellas Indication: Moderate to severe hot flashes caused by menopause Sounds like: A Broadway play Epkinly vs. Zurzuvae Epkinly Makers: AbbVie/Genmab Indication: Relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma after two or more lines of systemic therapy Sounds like: Someone who watches too many streaming episodes Zurzuvae Makers: Sage/Biogen Indication: Postpartum depression Sounds like: A mouthful Izervay vs. Talvey Izervay Maker: Iveric Bio Indication: Geographic atrophy secondary to age-related macular degeneration Sounds like: A new app for scanning the land Talvey Maker: Johnson & Johnson Indication: Relapsed or refractory multiple myeloma who have received at least four prior therapies Sounds like: A little too close to talc… Elrexfio vs. Veopoz Elrexfio Maker: Pfizer Indication: Relapsed or refractory multiple myeloma who have received at least four prior lines of therapy Sounds like: A new dinosaur found in Mexico Veopoz Maker: Regeneron Pharmaceuticals Indication: Patients 1 year old and older with CD55-deficient protein-losing enteropathy Sounds like: Double-plus good! Zilbrysq vs. Ojjaara Zilbrysq Maker: UCB Indication: Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive Sounds like: Absolute zero Ojjaara Maker: GSK Indication: Intermediate or high-risk myelofibrosis in adults with anemia Sounds like: “What’s my name?” Exxua vs. Pombiliti Exxua Maker: Fabre-Kramer Pharmaceuticals Indication: Major depressive disorder Sounds like: Someone who’s always leaving Pombiliti Maker: Amicus Indication: Late-onset Pompe disease Sounds like: The ability to treat Pompe disease (this feels a little on the nose) Rivfloza vs. Velsipity Rivfloza Maker: Novo Nordisk Indication: Urinary oxalate levels in patients 9 years and older with primary hyperoxaluria type 1 and relatively preserved kidney function Sounds like: An exuberant DJ Velsipity Maker: Pfizer Indication: Moderately to severely active ulcerative colitis in adults Sounds like: A deodorant brand you wouldn’t want to buy Bimzelx vs. Omvoh Bimzelx Maker: UCB Indication: Moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy Sounds like: Throwing away unwanted antacids Omvoh Maker: Eli Lilly Indication: Ulcerative colitis Sounds like: A new age prayer Loqtorzi vs. Defencath Loqtorzi Maker: Coherus Biosciences Indication: Recurrent or metastatic nasopharyngeal carcinoma when used together with or following other therapies Sounds like: How you close the door in a magical kingdom Defencath Maker: CorMedix Indication: Reduce the incidence of catheter-related bloodstream infections in adults with kidney failure receiving chronic hemodialysis Sounds like: A Dungeons and Dragons character Augtyro vs. Ryzneuta Augtyro Maker: Bristol Myers Squibb Indication: ROS1-positive non-small cell lung cancer Sounds like: A virtual reality game where you’re the bad guy Ryzneuta Maker: Acrotech Biopharma Indication: Neutropenia Sounds like: Getting rid of someone’s charisma Truqap vs. Ogsiveo Truqap Maker: AstraZeneca Indication: Breast cancer that meets certain disease criteria Sounds like: A limit on truth Ogsiveo Maker: SpringWorks Indication: Progressing desmoid tumors who require systemic treatment Sounds like: Oh, give us a go! Quviviq vs. Ztalmy Quviviq Maker: Idorsia Indication: Insomnia Sounds like: A producer asking a biotech founder turned politician to get ready for his TV appearance Ztalmy Maker: Marinus Indication: Seizures in cyclin-dependent kinase-like 5 deficiency disorder Sounds like: A nefarious Yevgeny Zamyatin character Opdualag vs. Wainua Opdualag Maker: Bristol Myers Squibb Indication: Unresectable or metastatic melanoma Sounds like: A Russian prison Wainua Maker: AstraZeneca Indication: Polyneuropathy of hereditary transthyretin-mediated amyloidosis Sounds like: A Premier League footballer

2023-10-28

·行舟Drug

2022年全球获批上市的原创新药：回顾与展望

点击上方的行舟Drug ▲ 添加关注摘要2022年生物医药全行业热力指数逐渐下行，但基因治疗、细胞治疗等细分赛道依然活跃，源头技术突破、多学科交叉整合创新加快了新药研发进程。2022年全球获批新药的种类丰富，一些重磅新药和新技术疗法为复杂疾病带来了新的治疗希望。美国FDA药品评估和研究中心（CDER）在2022年共批准了37款新药，其中25款为全球首次批准；欧洲EMA全年共批准了51款新药，其中8款为全球首次批准；日本PMDA全年共批准了48款新药，其中12款为全球首次批准；我国国家药品监督管理局（NMPA）全年共批准了40款新药，其中11款为全球首次批准。本文总结了2022年美国、欧洲、日本和中国获批上市的新药，并对2023年新药研发和生物医药发展态势进行展望。关键词：创新药；全球首批；细胞与基因治疗；孤儿药2022年在众多不确定因素的影响下，世界经济前景黯淡且存在不确定性，全球生物医药行业面临着前所未有的风险和挑战[1]。2022年全球新药获批数量较往年减少，但类别丰富，涉及靶向小分子药物、抗体药物、罕见病药物、细胞与基因治疗产品等，产品开发向“高含金量”方向发展，多种嵌合抗原受体T细胞（CAR⁃T）免疫疗法、程序性死亡受体1/程序性死亡受体⁃配体1（PD⁃1/PD⁃L1）、mRNA疫苗产品相继获批上市。本文对美国、欧洲、日本和我国2022年获批上市的新药进行梳理和重点介绍，包括新分子实体（NME）和新的治疗用生物制品（BLA），并对2023年新药研发和生物医药发展态势进行展望。2022年以前就已获批上市药物的相关仿制药、新剂型以及血液制品、中药、疫苗等产品不在本文讨论范围内。一2022年美国FDA批准的全新药物2022年美国FDA药品评估和研究中心（Center of Drug Evaluation and Research，CDER）共批准了37款新药（见表1），其中全球首批新药25款[2]。与往年批准新药近50款相比，2022年获批新药数量有所下降，但是创新的步伐并没有减缓，获批生物药15款，涉及单克隆抗体、双特异性抗体、抗体药物偶联物（antibody⁃drug conjugates，ADC）、T细胞受体嵌合型T细胞（TCR⁃T）疗法、酶替代疗法等，创3年新高。从适应证来看，抗肿瘤药物依然占据主导地位，其次是神经系统和皮肤药物。值得一提的是，37款新药中获得孤儿药资格认定的多达20款。从创新性上看，2022年CDER共批准了21款“first⁃in⁃class”疗法，超过新药获批总数的一半，其中10款获得突破性疗法认定。从审评方式看，37款新药中共有24款药物使用了1个或多个加速计划，其中快速通道12种，突破性治疗13种，优先审查21种，加速审批6种。美国FDA批准了多个领域的“首款”新药和创新疗法。例如治疗不可切除或转移性葡萄膜黑色素瘤的Kimmtrak是全球首款获批的T⁃细胞受体疗法（TCR疗法），实现了TCR疗法“从0到1”的突破[3]。针对百年顽疾肌萎缩侧索硬化症（ALS）的疗法Relyvrio，或将成为“渐冻症”患者群体新的希望。百时美施贵宝（BMS）公司的Sotyktu是美国FDA批准的首款酪氨酸激酶2（TYK2）抑制剂，将为中重度斑块型银屑病患者群体带来一种更为安全有效的一线口服治疗方案。此外，还有全球首款能够干预1型糖尿病进程的单克隆抗体药物Tzield，首款针对淋巴细胞活化基因3（LAG⁃3）的复方制剂Opdualag，以及4款针对罕见病的药物[小分子丙酮酸激酶激活剂Pyrukynd、用于治疗细胞周期依赖激酶样蛋白5（CDKL5）缺乏症相关的癫痫发作的Ztalmy、治疗成人遗传性转甲状腺素蛋白淀粉样变性伴多发性神经病（hATTR⁃PN）的Amvuttra、用于酸性鞘磷脂酶缺乏症（ASMD）的Xenpozyme]。2022年，美国FDA共批准了4款基因疗法，数量空前。此外，还批准了1款细胞疗法Carvykti和1款微生物疗法Rebyota。其中细胞疗法产品来自我国企业传奇生物公司，用于治疗成人复发/难治性多发性骨髓瘤。这是第一款获美国FDA批准上市的国产CAR⁃T细胞疗法，Carvykti的成功“出海”是我国创新药研发史上一件里程碑式的大事件。获美国FDA批准后不久，Carvykti分别于2022年5月和9月于欧洲和日本上市。Rebyota是美国FDA首次批准的粪便微生物组疗法，代表了微生物疗法的一大步，并为艰难梭菌感染（CDI）复发的治疗提供了新选择。二2022年欧洲批准的全新药物2022年欧洲EMA共批准了51款新药，涉及14个治疗领域，其中8款为全球首批新药（见表2）[4]。有2款小分子实体药物值得关注，分别是ObsEva公司研发的治疗子宫肌瘤的口服促性腺激素释放激素（GnRH）拮抗剂Yselty[5]和Gilead Sciences Inc. 的注射用抗艾滋病药物Sunlenca[6]，Sunlenca的优势在于简化了药物治疗方案。基因治疗、细胞治疗药物在欧盟被纳入先进技术治疗医学产品（ATMP）管理[7]。2022年欧洲EMA批准了3款基因治疗药物和3款细胞治疗药物，其中2款基因治疗药物和1款细胞治疗药物属于全球首批新药，它们分别是：PTC Therapeutics公司开发的用于治疗罕见病芳香族L⁃氨基酸脱羧酶（AADC）缺乏症的脑内注射基因疗法Upstaza、Bio⁃Marin Pharmaceutical公司开发的重型血友病A基因疗法Roctavian以及Atara Biotherapeutics与Pierre Fabre合作开发的同种异体T细胞疗法Ebvallo。值得一提的是，不同于已上市高度定制化的自体CAR⁃T疗法，Ebvallo使用来自供体的EB病毒T细胞，Ebvallo的获批是细胞治疗的一个里程碑式进展，也为EB病毒阳性移植后淋巴增生性疾病（EBV+PTLD）患者带来了新的希望。三2022年日本批准的全新药物2022年日本PMDA共批准48款新药，其中全球首次获批产品12个（见表3），包括8个化学药品和4个生物制品。获批新药的分子类型较多元，包含小分子药物、单抗、蛋白和肽等；治疗领域广泛，主要涉及抗恶性肿瘤、消化系统、呼吸系统、激素/代谢等领域；数量上虽然不及美国FDA，但在日本PMDA全球首批的12个新药中有一半是由日本本土药企自主研发。2022年5月，日本的“药品与医疗器械法”新增了应急批准制度，不仅适用于除日本外的国家药监部门已批准上市许可的品种，也同样适用于日本企业自主研发的新药。盐野义制药公司用于新型冠状病毒感染的抗病毒药物富马酸Ensitrelvir片是第一个通过应急批准制度程序获日本PMDA批准上市许可的药品[8]。获批新药中有几个亮点产品值得期待：辉瑞公司Ngenla的批准上市带来了一种长效、每周1次的治疗选择，有助于减轻儿童生长激素缺乏症（GHD）患儿及其亲人和护理者每日注射生长激素的负担。Samtasu是一种静脉利尿剂，为口服托伐普坦有困难的体液潴留患者提供了一种新的治疗选择。nemolizumab是全球首个获批上市的白细胞介素⁃31受体（IL⁃31R）α抗体药物，使瘙痒缓解患者比例提高近3倍。四2022年中国批准的全新药物近年我国不断进行创新药审评改革，进一步简化境外上市新药审批程序、优化药品临床试验审批流程等，加快了境外药物在中国上市的速度，也同时对中国创新药的发展带来了巨大利好。新《药品注册管理办法》中增加了4个药品注册快速通道，分别为突破性治疗药物、附条件批准、优先审评审批、特别审批[9]，这些举措推动了本土创新药研发的快速发展。2022年国家药品监督管理局（NMPA）共批准了40款新药[10]，包括27款化学药、13款生物药。全球首批的有11款（见表4），其中小分子化药6款、抗体5款。2022年获批数量较2021年有所下降，但其中不乏多个“首款”亮点药物值得关注：华领医药公司first⁃in⁃class降糖药多格列艾汀是全球范围内首个获批上市的葡萄糖激酶启动剂（GKA）药物，是过去近10年来糖尿病领域首个全新机制的原创新药。NMPA附条件批准康方生物公司的PD⁃1/CTLA⁃4双抗卡度尼利单抗是首款获批用于晚期宫颈癌的免疫治疗药物。绿叶制药公司的盐酸托鲁地文拉法辛缓释片是我国首个自主研发并拥有自主知识产权用于治疗抑郁症的化学药品1类创新药，也是目前全球唯一从药物作用机制到临床效果均被证实的多重再摄取抑制剂。华北制药公司的奥木替韦单抗是首个国内获批上市的用于成人狂犬病毒暴露者的被动免疫单抗药物。恒瑞医药公司的瑞维鲁胺是我国首个获批的国产新型雄激素受体（AR）抑制剂；璎黎药业公司的林普利塞片是我国首个获批的高选择性磷脂酰肌醇3⁃激酶（PI3K）δ抑制剂。2022年，抗新型冠状病毒口服药迎来曙光。2022年7月25日，我国NMPA附条件批准了首个国产新冠口服药阿兹夫定，还应急附条件批准了2款新冠口服药——辉瑞公司的Paxlovid和莫诺拉韦胶囊。五2023年生物医药领域展望 Evaluate Vantage近期发布的“Evaluate Vantage 2023 Preview”报告中预测[11]：阿尔茨海默病是2023年的重点领域之一，卫材公司和礼来公司都有望将其各自的清除淀粉样斑块的抗体推向市场，lecanemab和donanemab是2023年该领域最值得关注的药物。默克公司的PD⁃1靶向药物Keytruda将在2023年成为全球最畅销的药物，预计增加30亿美元的销售额。葛兰素史克（GSK）、辉瑞、强生（J&J）和Moderna等公司在呼吸道合胞病毒领域的作为也值得期待。除此之外，科睿唯安公司的2023年度药物观察报告中指出[12]，9种主要针对艾滋病毒、帕金森病、克罗恩病、脱发、多发性骨髓瘤和乳腺癌等重磅药物到2030年可能在中国实现10亿美元的销售额。近年来，罕见病正在成为生物制药行业追逐的新领地。GMI Insights近日发布的一份报告显示，2022年全球罕见病治疗市场规模超过1950亿美元，未来10年该市场估计复合年增长率（CAGR）超过8.5%，到2032年将达到4350亿美元。阿斯利康、辉瑞、罗氏等公司是罕见病药物的巨头，辉瑞公司已有超过5款新分子实体和3款基因疗法项目已经进入Ⅲ期临床试验阶段。2022年1月，NMPA药品审评中心（CDE）发布了《罕见疾病药物临床研发技术指导原则》，从国家层面为罕见病药物研发企业指明了方向。NMPA全年共批准12款罕见病药物上市，增速平稳。近期发布的2022年国家医保药品目录新增利司扑兰等7个罕见病用药，现共有73种药物纳入医保，涉及31种罕见病[13]。越来越多罕见病药物上市并纳入医保使我国罕见病患者的用药环境持续改善。六结语近年来，大数据与人工智能[14]、基因编辑[15]、细胞疗法[16]等新兴技术和疗法在制药领域的深度交叉融合，医药产业新理念、新技术、新模式和新业态不断涌现，深刻影响了全球新药研发的思路和方向，推动创新药研发进入变革时代。得益于政策、人才、资本、企业等多重利好叠加，近年来我国医药产业创新能力显著提高，与全球制药强国在创新和品种的研发能力、新产品数量的差距正在逐步缩小，新药开发正在实现从“量”到“质”的飞跃。国内的创新药企业也开始走出国门，加速开拓海外市场，从年初传奇生物公司CAR⁃T在美国顺利上市，到年末康方生物公司双抗以50亿美元成功对外授权，中国制药企业开始在全球市场崭露头角。随着政策红利持续加码、医药研发新技术的迭代升级、全球商业化格局的演变，中国制药企业国际化道路充满机遇与挑战，任重而道远。参考文献[1]United Nations. World Economic Situation and Prospects 2023[EB/0L].( 2023 )[2023 - 04 - 11]. htps://www. un.org/development/desa/dpad/publication/world-economic-situationand.prospecls-2023/.[2]FDA. Novel Drug Approvals for 2022 [ EB/OL].( 2023 - 01 -10)[2023 - 04 - 07 ]. htps://www. fda. gov/drugs/new-drugsfda-cders-new-molecular-entities-and-new-therapeutic-biological-producls/novel-drug-approvals-2022.[3]FDA. FDA approves tebentafusp-tebn for unreseclable or metastatic uveal melanomal EB/OL] .( 2023 - 01 - 10)[ 2023 - 04 07 ]. https ://www. fda. gow/drugs/resources-information-approveddrugs/fda-approves-tebent ausp-tebn-unresectable-or-melaslatic-uveal-melanoma.[4]EMA. Human Medicines Highlights 2022[ EB/OL].(2023 - 0216)[2023 - 04 - 07 ]. https :// www. ema. europa. eu/en/newshuman-medicines-highlights-2022 .[5]ObsEva Press Release. ObsEva Announces European CommissionMarketing Authorization for YseltyW ( linzagolix ) , an Oral GnRHAntagonist , for the Treatment of Uterine Fibroids [ EB/OL ](2022 -06 -17)[ 2023 - 04 - 07 ].htps://www. obseva. compressrelease-delail/? pr = 5038. Accessed 14 NOV 2022 7.[6]Biospace. Gilead Scores First Approval for Twice-Yearly HIV Drugin Lalest Advance[ EB/0L].(2022 - 08 - 22)[2023 - 04 - 07 ]https://link. zhihu. com/? target = https% 3A//www. biospacecom/article/eu-approval-for-gilead-s-sunlenca-addresses-unmel-need-in-multi-drug-resistant-hiv/.[7]陈云.李珊珊.邵蓉,等.欧洲前沿疗法药物的监管、审批及其启示[J].中国新药杂志,2020,29(15):1681 -1690.[8]王欢,王宏亮,谢菲.首个口服非共价、非肤性严重急性呼吸综合征冠状病毒 23CL蛋白酶抑制剂一Ensitrelvir[J].临床药物治疗杂志,2022,20(8):17 -21.[9]陈新.温宝书.浅谈新法规框架下药品加快上市注册程序变化[J].中国食品药品监管,2020(8):18 - 22.[10]医药魔方。2022 年中国新药注册审评报告[EB/OL].( 2023 -02 )[2023 - 04 - 07 ]. https ://www. pharmcube. com/product/report /index.[11]Evaluate. Evaluate Vantage 2023 Preview[ EB/0L]( 2022 - 04 -11)[2023 - 04 - 07 ]. https ://www. evaluate. com/thought-leader-ship/vanlage/evaluate-vantage-2023-preview? um source = markelo&utm medium = email&utm _campaign = 2023Preview Webinar&utmcontent = content hub.[12]Clarivate.科睿唯安发布年度《最值得关注的药物预测》报告聚焦 2023 年15 种潜在重磅炸弹药物[ EB/OL].(2022 -01 - 11)[2023 - 04 - 07 ]. https ://clarivate. com. cn/2023/01/11/thedrugs-to-watch-in-2023 /.[13]中新网.73 种军见病药物纳人医保,涉及 31 个病种[EB/0L].( 2023 - 02 - 28) 2023 - 04 - 11]. hup://www. chi-nanews. com. cn/sh/2023/02-28/9961854.shtml.[14]郑明月.蒋华良.高价值数据挖掘与人工智能技术加速创新药物研发[J].药学进展,2021,45(7) :481 -483.[15]杨若南.许丽.李伟,等.2022 年基因治疗领域发展态势[J]生命科学_2023 ,35( 1):95 - 102.[16]秒香.高鹏翼.郑浩呈,等.CART 细胞疗法新兴治疗的前沿进展[]].中国医药导刊,2022,24(10):974 -982.文章信息源于公众号注册圈，登载该文章目的为更广泛的传递行业信息，不代表赞同其观点或对其真实性负责。文章版权归原作者及原出处所有，文章内容仅供参考。本网拥有对此声明的最终解释权，若无意侵犯版权，请联系小编删除。学如逆水行舟，不进则退；心似平原走马，易放难收。行舟Drug每日更新欢迎订阅+医药大数据|行业动态|政策解读

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外链

KEGG	Wiki	ATC	Drug Bank
D10820	-	-	DB12835

研发状态

批准上市

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适应症	国家/地区	公司	日期
酸性鞘磷脂酶缺乏症	日本	Sanofi KK	2022-03-28

未上市

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适应症	最高研发状态	国家/地区	公司	日期
A型尼曼匹克病	临床3期	美国	Genzyme Corp.	2015-12-18
A型尼曼匹克病	临床3期	日本	Genzyme Corp.	2015-12-18
A型尼曼匹克病	临床3期	阿根廷	Genzyme Corp.	2015-12-18
A型尼曼匹克病	临床3期	澳大利亚	Genzyme Corp.	2015-12-18
A型尼曼匹克病	临床3期	比利时	Genzyme Corp.	2015-12-18
A型尼曼匹克病	临床3期	巴西	Genzyme Corp.	2015-12-18
A型尼曼匹克病	临床3期	保加利亚	Genzyme Corp.	2015-12-18
A型尼曼匹克病	临床3期	智利	Genzyme Corp.	2015-12-18
A型尼曼匹克病	临床3期	法国	Genzyme Corp.	2015-12-18
A型尼曼匹克病	临床3期	德国	Genzyme Corp.	2015-12-18

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适应症

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EHA2023	N/A	酸性鞘磷脂酶缺乏症	-	Olipudase alfa	鹹鬱簾淵醖襯壓鏇範網(鏇選觸鏇觸窪顧鏇憲餘) = 選糧願繭製鏇憲襯願網蓋廠齋壓鹹夢蓋蓋壓範 (膚獵夢鬱夢築繭糧壓蓋, 7.3) 更多	-	2023-06-08
SSIEM2022	N/A	酸性鞘磷脂酶缺乏症	60	Olipudase alfa	糧構鏇願鑰顧鏇鑰構淵(餘醖壓顧範鬱糧選壓築) = 糧壓獵襯蓋醖選範艱構範餘範選膚醖築繭襯夢 (獵鏇醖鹹構鏇蓋觸鹹獵, ±15.6)	-	2022-08-30
NCT02004691 (ASCEND, EHA2022)	临床2/3期	酸性鞘磷脂酶缺乏症	36	Olipudase alfa	鏇製夢廠鏇壓蓋壓繭構(廠繭選蓋鏇鏇築築糧艱) = 獵醖廠淵製夢艱築壓顧遞鏇繭衊齋夢簾構選簾 (願構網範壓餘鹽餘繭齋, 6.2) 更多	-	2022-06-10
NCT02004691 (ASCEND, Pubmed \| Genet Med) 人工标引	临床2/3期	酸性鞘磷脂酶缺乏症	36	Olipudase alfa	壓範窪憲鏇選願壓遞鹹(構壓壓繭餘顧鑰顧網積) = 糧網願選繭鹽衊鹽觸艱獵願觸顧築襯選繭鹽觸 (艱簾網簾觸淵齋廠鏇鹹 ) 更多	积极	2022-04-26
				Placebo	壓範窪憲鏇選願壓遞鹹(構壓壓繭餘顧鑰顧網積) = 憲製範餘艱餘鏇鏇鹽鑰獵願觸顧築襯選繭鹽觸 (艱簾網簾觸淵齋廠鏇鹹 ) 更多
NCT02004704 (GlobeNewswire) 人工标引	临床3期	酸性鞘磷脂酶缺乏症	25	Olipudase alfa (Adult)	窪簾糧淵膚憲鏇鹹願鑰(鏇觸衊製簾構襯餘壓鹹) = 7 events were observed in four patients: one patient had an anaphylactic reaction but restarted treatment after tailored desensitization and reached the target dose; one patient had two events of transient alanine aminotransferase elevation; one patient had urticaria and rash; and one patient had two hypersensitivity reactions. 淵繭艱齋鬱築鬱齋積壓 (衊餘夢膚艱繭蓋膚膚顧 ) 更多	积极	2022-02-09
				Olipudase alfa (Pediatric)
EHA2021	N/A	酸性鞘磷脂酶缺乏症	-	Olipudase alfa	糧淵夢鏇醖遞繭選願獵(繭範鑰構遞鏇夢繭齋齋) = 願製艱衊醖構鏇膚構製廠製淵鏇網憲憲餘鹽廠 (夢選壓顧夢膚衊衊築選 ) 更多	-	2021-06-09
				Placebo	糧淵夢鏇醖遞繭選願獵(繭範鑰構遞鏇夢繭齋齋) = 構網鹽鹹獵廠憲憲窪鏇廠製淵鏇網憲憲餘鹽廠 (夢選壓顧夢膚衊衊築選 )
NCT02292654 (CTgov)	临床1/2期	酸性鞘磷脂酶缺乏症 \| A型尼曼匹克病	20	Olipudase Alfa (Olipudase Alfa: Adolescent Cohort)	衊鏇選觸鹽艱繭選衊願(夢鹽構築醖糧廠顧夢壓) = 膚範窪齋艱鬱鹽艱鹹製壓齋齋願遞齋淵鏇築範 (簾鏇衊鬱鑰選膚齋壓醖, 構鹹鹹鏇範淵壓窪選繭 ~ 鑰蓋積窪壓糧網齋糧願) 更多	-	2021-02-01
				Olipudase Alfa (Olipudase Alfa: Child Cohort)	衊鏇選觸鹽艱繭選衊願(夢鹽構築醖糧廠顧夢壓) = 網艱夢憲遞淵醖壓遞願壓齋齋願遞齋淵鏇築範 (簾鏇衊鬱鑰選膚齋壓醖, 獵糧廠範選鏇範鹽淵廠 ~ 鹹鑰糧艱製築選鑰製廠) 更多
ASCEND (Biospace) 人工标引	N/A	酸性鞘磷脂酶缺乏症	36	Olipudase alfa	憲襯繭醖鹹窪觸網製網(醖醖鏇淵觸願鬱鬱衊遞) = 鬱廠選築窪鹹憲艱憲衊夢鑰積網網範鹽淵蓋醖 (醖鹹顧壓壓選遞遞鬱鏇 ) 更多	积极	2020-01-30
				Placebo	憲襯繭醖鹹窪觸網製網(醖醖鏇淵觸願鬱鬱衊遞) = 築夢憲壓膚積窪範窪壓夢鑰積網網範鹽淵蓋醖 (醖鹹顧壓壓選遞遞鬱鏇 ) 更多
NCT02004704 (Pubmed) 人工标引	临床2期	酸性鞘磷脂酶缺乏症	5	Olipudase alfa	鑰餘餘衊齋餘鑰鏇遞窪(願觸淵糧簾積網窪鬱醖) = The majority of adverse events were mild and included headache, nausea, and abdominal pain 製憲網糧願襯蓋壓夢夢 (鹹觸醖夢糧糧醖窪築獵 )	积极	2018-09-01
NCT01722526 (Pubmed \| Mol Genet Metab)	临床1期	酸性鞘磷脂酶缺乏症	5	Olipudase alfa	構齋獵憲淵觸選齋廠廠(夢齋廠壓獵繭繭蓋簾淵) = 繭夢積衊窪選鬱艱窪簾網網廠餘襯廠鑰壓鹹夢 (襯積選壓艱壓鏇衊遞壓 ) 更多	-	2015-09-30