A Long-term Multicenter Prospective Observational Study Evaluating the Comparative Effectiveness and Safety of Sarepta Gene Transfer Therapy vs. Standard of Care in Participants With Duchenne Muscular Dystrophy Under Conditions of Routine Clinical Practice

This is a multicenter, prospective, observational Phase 4 study in the United States. The study is designed to collect both medical history and prospective data on Duchenne muscular dystrophy (DMD) treatment outcomes in participants receiving delandistrogene moxeparvovec as part of clinical care, compared to participants with DMD receiving or prescribed to start chronic glucocorticoid treatment at baseline in routine clinical practice. In addition, treatment outcomes will be collected prospectively from post-trial participants who have received delandistrogene moxeparvovec through participation in select SRP-9001 studies.

开始日期2024-02-07

申办/合作机构

Sarepta Therapeutics, Inc.

NCT06241950 / Active, not recruiting临床1期

An Open-Label, Systemic Gene Delivery Study to Evaluate the Safety, Tolerability and Expression of SRP-9001 in Association With Imlifidase in Subjects With Duchenne Muscular Dystrophy With Pre-existing Antibodies to rAAVrh74

This is a gene transfer therapy study evaluating the safety of delandistrogene moxeparvovec and delandistrogene moxeparvovec dystrophin expression in association with imlifidase, in participants with DMD with pre-existing antibodies to rAAVrh74 over a period of 104 weeks.

开始日期2024-01-29

申办/合作机构

Sarepta Therapeutics, Inc.

[+1]

NCT06128564 / Recruiting临床2期

A Two-Part, Open-Label Systemic Gene Delivery Study to Evaluate the Safety and Expression of RO7494222 (SRP-9001) in Subjects Under the Age of Four With Duchenne Muscular Dystrophy

This open-label, single-arm study will evaluate the safety and expression of delandistrogene moxeparvovec in participants with DMD. Participants will be in the study for approximately 264 weeks.

开始日期2023-11-29

申办/合作机构

Hoffmann-La Roche Ltd.

[+1]

100 项与 Delandistrogene moxeparvovec 相关的临床结果

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100 项与 Delandistrogene moxeparvovec 相关的转化医学

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100 项与 Delandistrogene moxeparvovec 相关的专利（医药）

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项与 Delandistrogene moxeparvovec 相关的文献（医药）

2024-04-01·Pediatric neurology

Practical Considerations for Delandistrogene Moxeparvovec Gene Therapy in Patients With Duchenne Muscular Dystrophy

Article

作者: Mendell, Jerry R ; Darton, Eddie ; McDonald, Craig M ; Mason, Stefanie ; Murphy, Alexander P ; Mercuri, Eugenio ; Muntoni, Francesco ; Zaidman, Craig M ; Proud, Crystal ; Wang, Shufang ; Wandel, Christoph

BACKGROUND:

Delandistrogene moxeparvovec is a gene transfer therapy approved in the United States, United Arab Emirates, and Qatar for the treatment of ambulatory patients aged four through five years with a confirmed Duchenne muscular dystrophy (DMD)-causing mutation in the DMD gene. This therapy was developed to address the underlying cause of DMD through targeted skeletal, respiratory, and cardiac muscle expression of delandistrogene moxeparvovec micro-dystrophin, an engineered, functional dystrophin protein.

METHODS:

Drawing on clinical trial experience from Study 101 (NCT03375164), Study 102 (NCT03769116), and ENDEAVOR (Study 103; NCT04626674), we outline practical considerations for delandistrogene moxeparvovec treatment.

RESULTS:

Before infusion, the following are recommended: (1) screen for anti-adeno-associated virus rhesus isolate serotype 74 total binding antibody titers <1:400; (2) assess liver function, platelet count, and troponin-I; (3) ensure patients are up to date with vaccinations and avoid vaccine coadministration with infusion; (4) administer additional corticosteroids starting one day preinfusion (for patients already on corticosteroids); and (5) postpone dosing patients with any infection or acute liver disease until event resolution. Postinfusion, the following are recommended: (1) monitor liver function weekly (three months postinfusion) and, if indicated, continue until results are unremarkable; (2) monitor troponin-I levels weekly (first month postinfusion, continuing if indicated); (3) obtain platelet counts weekly (two weeks postinfusion), continuing if indicated; and (4) maintain the corticosteroid regimen for at least 60 days postinfusion, unless earlier tapering is indicated.

CONCLUSIONS:

Although the clinical safety profile of delandistrogene moxeparvovec has been consistent, monitorable, and manageable, these practical considerations may mitigate potential risks in a real-world clinical practice setting.

2024-01-01·Muscle & nerve

Long‐term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial

Article

作者: Alfano, Lindsay N ; Mendell, Jerry R ; Potter, Rachael A ; Shell, Richard ; Lowes, Linda P ; Mason, Stefanie ; Lehman, Kelly J ; Church, Kathleen ; Rodino-Klapac, Louise R ; Griffin, Danielle A ; Sahenk, Zarife ; Iammarino, Megan A ; Reash, Natalie F ; Wang, Shufang ; Darton, Eddie ; Lewis, Sarah ; Hogan, Mark

Abstract:

Introduction/Aims:

Delandistrogene moxeparvovec is indicated in the United States for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. Long‐term delandistrogene moxeparvovec microdystrophin protein (a shortened dystrophin that retains key functional domains of the wild‐type protein) expression may positively alter disease progression in patients with DMD. We evaluated long‐term safety and functional outcomes of delandistrogene moxeparvovec in patients with DMD.

Methods:

An open‐label, phase 1/2a, nonrandomized controlled trial (Study 101; NCT03375164) enrolled ambulatory males, ≥4 to <8 years old, with DMD. Patients received a single intravenous infusion (2.0 × 1014 vg/kg by supercoiled quantitative polymerase chain reaction) of delandistrogene moxeparvovec and prednisone (1 mg/kg/day) 1 day before to 30 days after treatment. The primary endpoint was safety. Functional outcomes were change from baseline in North Star Ambulatory Assessment (NSAA) and timed function tests.

Results:

Four patients (mean age, 5.1 years) were enrolled. There were 18 treatment‐related adverse events; all occurred within 70 days posttreatment and resolved. Mean NSAA total score increased from 20.5 to 27.5, baseline to year 4, with a mean (standard deviation) change of +7.0 (2.9). Post hoc analysis demonstrated a statistically significant and clinically meaningful 9‐point difference in NSAA score, relative to a propensity‐score–weighted external control cohort (least‐squares mean [standard error] = 9.4 [3.4]; P = .0125).

Discussion:

Gene transfer therapy with delandistrogene moxeparvovec treatment is well tolerated, with a favorable safety profile. Functional improvements are sustained through 4 years, suggesting delandistrogene moxeparvovec may positively alter disease progression.

2023-12-31·Journal of market access & health policy

Assessing the value of delandistrogene moxeparvovec (SRP-9001) gene therapy in patients with Duchenne muscular dystrophy in the United States

Article

作者: Malone, Daniel C ; Mendell, Jerry R ; Gooch, Katherine L ; Sedita, Lauren E ; McDonald, Craig M ; Klimchak, Alexa C ; Rodino-Klapac, Louise R

Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene therapy that may delay progression of Duchenne muscular dystrophy (DMD), a severe, rare neuromuscular disease caused by DMD gene mutations. Early cost-effectiveness analyses are important to help contextualize the value of gene therapies for reimbursement decision making. Objective: To determine the potential value of delandistrogene moxeparvovec using a cost-effectiveness analysis. Study design: A simulation calculated lifetime costs and equal value of life years gained (evLYG). Inputs included extrapolated clinical trial results and published utilities/costs. As a market price for delandistrogene moxeparvovec has not been established, threshold analyses established maximum treatment costs as they align with value, including varying willingness-to-pay up to $500,000, accounting for severity/rarity. Setting: USA, healthcare system perspective Patients: Boys with DMD Intervention: Delandistrogene moxeparvovec plus standard of care (SoC; corticosteroids) versus SoC alone Main outcome measure: Maximum treatment costs at a given willingness-to-pay threshold Results: Delandistrogene moxeparvovec added 10.30 discounted (26.40 undiscounted) evLYs. The maximum treatment cost was approximately $5 M, assuming $500,000/evLYG. Varying the benefit discount rate to account for the single administration increased the estimated value to #$5M, assuming $500,000/evLYG. Conclusion: In this early economic model, delandistrogene moxeparvovec increases evLYs versus SoC and begins to inform its potential value from a healthcare perspective.

353

项与 Delandistrogene moxeparvovec 相关的新闻（医药）

2024-06-17

·PRNewswire

Pfizer's Setback in Duchenne Muscular Dystrophy Treatment Trial Clears Path for Sarepta, and Many Other Pharma Companies | DelveInsight

Pfizer's mini-dystrophin gene therapy fordadistrogene movaparvovec failure in the Duchenne muscular dystrophy treatment opens new opportunities for several pharmaceutical companies such as Sarepta Therapeutics (SRP-5051), Santhera Pharmaceuticals/ReveraGen BioPharma (Vamorolone), Taiho Pharmaceutical (TAS-205), FibroGen (Pamrevlumab), and others, to advance their therapies and potentially dominate the DMD market. LAS VEGAS, June 17, 2024 /PRNewswire/ -- Duchenne muscular dystrophy is the most prevalent type of muscular dystrophy found in children. This genetic condition leads to ongoing muscle weakening and degeneration. It is one among nine different forms of muscular dystrophy. According to DelveInsight's estimates, the US accounted for around ~17K total prevalent cases of Duchenne muscular dystrophy in 2023. The highest cases were found in the children of the 5-9 age group, these numbers are expected to grow by the year 2034. As per DelveInsight's analysis, the most commonly associated comorbidities accompanied with DMD included the highest cases of scoliosis accounting for around ~20% of cases followed by ADHD, cardiomyopathy, and obsessive-compulsive disorders accounting for around ~19%, ~18%, and ~15% cases respectively in the US in the year 2023. The standard of care for DMD typically involves a combination of corticosteroids and surgical interventions. Prednisone and deflazacort are commonly prescribed glucocorticoids that have been utilized for over two decades to increase muscular strength in DMD patients. Surgery may be necessary to address contractures, spinal curvature, or scoliosis, which can affect breathing and overall mobility. Additionally, interventions such as pacemakers or other cardiac devices may be utilized to improve heart function. Sarepta Therapeutics is a key player in the DMD market, boasting three approved assets and two in the current pipeline. Despite its dominance, emerging competition is evident. The historical success rate for market entry varies across the 7MM. Notably, the DMD market exhibits geographic disparities in regulatory approvals, with instances of products approved in one jurisdiction and rejected in another, despite identical clinical data, reflecting the distinct standards of regulatory bodies such as EMA and FDA. Learn more about the FDA-approved DMD drugs @ Drugs for Duchenne Muscular Dystrophy Treatment The current US DMD treatment market possesses approved products, EMFLAZA (deflazacort), VYONDYS 53 (golodirsen), EXONDYS 51 (eteplirsen), AMONDYS 45 (casimersen), and VILTEPSO (viltolarsen), ELEVIDYS (delandistrogene moxeparvovec) in patients with DMD. In January 2024, Santhera Pharmaceuticals announced the introduction of its AGAMREE (vamorolone) to treat DMD patients aged four years and above in Germany. Santhera Pharmaceuticals has officially entered the commercial stage of its biopharma journey with the launch of this drug in Germany. ELEVIDYS, the first FDA-approved gene therapy for DMD, received accelerated approval in June 2023. However, ICER recently challenged the potential conversion of Sarepta's gene therapy to full approval, citing concerns about the surrogate endpoint used in the approval process. In the EU4 and the UK, the current market is dominated by steroid therapies along with an approved medication targeting DMD patients with the nonsense mutation, TRANSLARNA (ataluren). In Japan, the only approved treatment is VILTEPSO (viltolarsen). ELEVIDYS is a prescription gene therapy designed for ambulatory children aged 4 to 5 years with DMD and a confirmed dystrophin gene mutation. It received accelerated approval. Patients will take oral corticosteroids before and after receiving ELEVIDYS and will have weekly blood tests to monitor liver enzyme levels for three months post-treatment. In June 2023, the USFDA approved ELEVIDYS as the first gene therapy for treating pediatric patients aged 4-5 years with Duchenne Muscular Dystrophy and a confirmed DMD gene mutation. VYONDYS 53, developed by Sarepta Therapeutics, is prescribed for treating DMD in patients with a specific mutation of the DMD gene that can be addressed by exon 53 skipping. This approval is under the accelerated approval pathway, based on the observed increase in dystrophin production in the skeletal muscle of patients treated with VYONDYS 53. The FDA approved VYONDYS 53 (golodirsen) in December 2019. Additionally, the FDA granted VYONDYS 53 (golodirsen) New Chemical Entity (NCE) exclusivity until December 2024 and Orphan Drug Exclusivity until December 2026. To know more about DMD treatment options, visit @ New Treatment for Duchenne Muscular Dystrophy The DMD market is crowded with so many companies including FibroGen, Santhera Pharmaceutical, Italfarmaco, ReveraGen BioPharma, Cumberland Pharmaceuticals, Sarepta Therapeutics, Antisense Therapeutics, Capricor Therapeutics, and others are running clinical trials to improve the treatment space. The DMD pipeline possesses potential drugs in mid-stage developments to be launched shortly. Some of the promising drugs in the pipeline include Pizuglanstat (TAS-205), SRP-5051, Allogeneic Cardiosphere-derived Cells (CAP-1002), ITF2357 (Givinostat), and others that hold the potential to create a significant positive shift in the DMD market size. Discover which therapies are expected to grab major DMD market share @ Duchenne Muscular Dystrophy Market Report Italfarmaco is developing Givinostat (ITF2357), an oral small molecule that functions as a histone deacetylase inhibitor with potential anti-inflammatory, anti-angiogenic, and antineoplastic properties. ITF2357 increases the production of follistatin protein in muscle cells by inhibiting the HDAC enzyme, leading to increased muscle mass and prevention of muscle degeneration. This action counters the effects of myostatin, helping to alleviate the symptoms of DMD. Givinostat is currently in Phase III trials. The FDA has granted it Orphan Drug, Rare Pediatric Disease, and Fast Track designations for DMD treatment. Additionally, the European Commission has designated Givinostat as an Orphan Medicinal Product for DMD treatment. TAS-205 (pizuglanstat) is a selective inhibitor of hematopoietic prostaglandin D synthase (HPGDS), developed by Taiho Pharmaceutical. It is being advanced as a treatment for Duchenne muscular dystrophy (DMD), effective irrespective of the type of dystrophin gene mutation. By inhibiting HPGDS, which worsens the inflammatory response in the muscles of DMD patients, it helps control the decline in motor function. Currently, it is in Phase III of clinical trials. Discover more about drugs for DMD in development @ Duchenne Muscular Dystrophy Clinical Trials The anticipated launch of these emerging therapies for Duchenne muscular dystrophy are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the Duchenne muscular dystrophy market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for DMD is expected to grow from USD 2.1 billion in 2023 with a significant CAGR by 2034. The growth of the DMD market is expected to be mainly driven by increased diagnosed incidence, patient awareness, and a robust clinical pipeline during the forecast period (2024–2034). DelveInsight's latest published market report titled as Duchenne Muscular Dystrophy Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the DMD country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The DMD market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Prevalent Cases of Duchenne Muscular Dystrophy Age-specific Cases of Duchenne Muscular Dystrophy Ambulatory and Non-ambulatory Cases of Duchenne Muscular Dystrophy Mutation-specific Cases of Duchenne Muscular Dystrophy Associated Comorbidities in Duchenne Muscular Dystrophy The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM DMD market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this DMD market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the DMD market. Also, stay abreast of the mitigating factors to improve your market position in the DMD therapeutic space. Related Reports Duchenne Muscular Dystrophy Epidemiology Forecast Duchenne Muscular Dystrophy Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted Duchenne muscular dystrophy epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Duchenne Muscular Dystrophy Pipeline Duchenne Muscular Dystrophy Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Duchenne muscular dystrophy companies, including Santhera Pharmaceuticals, Sarepta Therapeutics, Italfarmaco, Wave Life Sciences Ltd, FibroGen, Edgewise Therapeutics, Pfizer, Daiichi Sankyo, Sarepta Therapeutics, Inc., ENCell, Taiho Pharmaceutical, Solid Biosciences, Capricor, Nippon Shinyaku, Hansa Biopharma, Ultragenyx Pharmaceutical, Dyne Therapeutics, Entrada Therapeutics, AAVogen, PepGen, Antisense Therapeutics, BioMarin Pharmaceutical, Avidity Biosciences, Sarepta Therapeutics, Dyne Therapeutics, Solid Biosciences Inc, Regenxbio, Stealth BioTherapeutics, among others. Nonsense Mutation Duchenne Muscular Dystrophy Pipeline Nonsense Mutation Duchenne Muscular Dystrophy Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key nonsense mutation Duchenne muscular dystrophy companies, including Taiho Pharmaceutical, Solid Biosciences, Capricor, Nippon Shinyaku, among others. Becker Muscular Dystrophy Pipeline Becker Muscular Dystrophy Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key becker muscular dystrophy companies, including Epirium Bio, Ultragenyx, Strykagen, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

临床3期上市批准孤儿药快速通道

2024-06-17

·BioSpace

FDA Action Alert: Merck, BMS, Sarepta and More

Pictured: A scientist with pill bottles in front of FDA headquarters/Taylor Tieden for BioSpace With six target action dates lined up, the FDA has a very busy week ahead. The regulator is expected to release decisions on drug applications for a pneumococcal vaccine, a gene therapy for Duchenne muscular dystrophy and a label expansion for one of cancer’s cornerstone therapies. Read below for more. Merck Awaits Verdict on Pneumococcal Shot Merck is seeking approval for its investigational 21-valent vaccine, dubbed V116, to prevent invasive pneumococcal disease and pneumococcal pneumonia in adults. The FDA is expected to release its verdict on June 17. The pharma is backing its regulatory bid with data from the Phase III STRIDE-3 trial, which in November 2023 showed that V116 induced non-inferior immune responses as compared with a 20-valent comparator vaccine. Merck is also supporting V116’s application with several other studies, including STRIDE-3, STRIDE-4, STRIDE-5 and STRIDE-6. Data from additional studies will be shared at future medical meetings. If approved, Merck’s vaccine would become the first pneumococcal conjugate shot designed specifically for use in adults. Argenx Seeks Approval for Vyvgart Hytrulo in CIDP Argenx is proposing to use its antibody fragment Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) to treat the rare autoimmune disease chronic inflammatory demyelinating polyneuropathy (CIDP). The FDA’s decision is due on June 21. The Netherlands-based biotech is supporting its supplemental Biologics License Application (sBLA) with data from the Phase II ADHERE study, which demonstrated a 61% reduction in the risk of relapse after treatment with Vyvgart Hytrulo versus placebo. In ADHERE’s open-label phase, 67% of patients showed evidence of clinical improvement. Vyvgart Hytrulo is a subcutaneous formulation of the human IgG1 antibody fragment efgartigimod alfa, combined with the recombinant human hyaluronidase PH20, which allows its subcutaneous administration. The drug was approved in June 2023 for the treatment of generalized myasthenia gravis. BMS Targets Krazati Expansion into CRC In February 2024, the FDA accepted Bristol Myers Squibb’s supplemental New Drug Application (sNDA) for its KRAS blocker Krazati (adagrasib), in combination with cetuximab, for the treatment of locally advanced or metastatic colorectal cancer (CRC). The deadline for the regulator’s decision is June 21. The application, which seeks to make Krazati a treatment option for CRC patients with KRAS G12C-mutated CRC, is supported by data from the KRYSTAL-1 study. BMS reported data from this trial in March 2024, touting a 34% objective response rate at a median follow-up of 11.9 months. Median progression-free survival was 6.9 months, while median overall survival reached 15.9 months. Krazati is an orally available small molecule inhibitor of G12C-mutated KRAS that won the FDA’s accelerated approval in December 2022. It was originally developed by Mirati Therapeutics, which BMS acquired in October 2023 for $4.8 billion. Harmony Aims for Wakix Expansion into Pediatric Narcolepsy Harmony Biosciences is proposing its oral drug Wakix (pitolisant) as a treatment for excessive daytime sleepiness in pediatric narcolepsy patients aged 6 years and above. The FDA’s deadline for a decision is June 21. In its sNDA, Harmony provided data from a Phase III multicenter, randomized and placebo-controlled study evaluating the efficacy and safety of Wakix in narcolepsy patients ages six through 17 with or without cataplexy. The FDA granted the application its priority review status. Wakix is an orally available histamine 3 receptor antagonist. It was approved by the FDA in August 2019 for the treatment of excessive daytime sleepiness of adult narcolepsy. Merck Targets Addition to Growing List of Keytruda Indications By June 21, the FDA is expected to release its verdict on Merck’s sBLA proposing to use its blockbuster PD-1 inhibitor Keytruda, in combination with standard of care chemotherapy, as a treatment for primary advanced or recurrent endometrial carcinoma. Merck is supporting its bid for the additional indication with results from the Phase III NRG-GY018 study, which found that the Keytruda-based investigational regimen cut the risk of disease progression or death by 46% in patients whose disease was mismatch repair proficient. Meanwhile, those with mismatch repair deficient disease saw a 70% reduction in the risk of progression or death versus chemotherapy alone. If approved, Keytruda would become the “first immunotherapy indicated for the frontline treatment of advanced endometrial cancer regardless of mismatch repair status,” Gursel Aktan, vice president of global clinical development at Merck Research Laboratories, said in a statement accompanying the sBLA’s acceptance in February 2024. Sarepta Seeks Full Approval for DMD Gene Therapy Despite Shaky Data In February 2024, the FDA accepted an efficacy supplement to Sarepta Therapeutics’ sBLA seeking to convert the accelerated approval of its gene therapy Elevidys (delandistrogene moxeparvovec-rokl) into traditional approval, as well as broaden its label to include all Duchenne muscular dystrophy (DMD) patients with confirmed DMD gene mutations. The FDA’s decision is due on June 21. Currently, Elevidys is only indicated for ambulatory pediatric patients aged 4 through 5 years of age. The FDA granted Elevidys accelerated approval in June 2023, a decision that has recently come under fire, particularly as the gene therapy failed its primary efficacy endpoint in part 1 of the SRP-9001-102 study, unable to significantly outdo placebo in terms of patients’ functional performance. Sarepta’s bid for full approval is supported by the Phase III EMBARK study, which in October 2023 also fell short of its primary endpoint. In patients treated with Elevidys, scores on the North Star Ambulatory Assessment tool at 52 weeks were only 0.65 points higher than placebo comparators, an effect that did not satisfy statistical significance. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

临床3期临床结果上市批准临床2期优先审批

2024-06-14

·药融圈

辉瑞DMD基因疗法3期临床失败

▲8月15-16日 NDC2024生物医药创新者峰会扫码立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。 6月12日，辉瑞宣布其杜氏肌营养不良症基因疗法PF-06939926的III期临床CIFFREO失败，与安慰剂相比，PF-06939926在III期试验中未达到主要和关键次要终点。杜氏肌营养不良症（DMD）是一种罕见且严重的遗传性肌肉疾病，由抗肌萎缩蛋白基因突变导致。患者通常在5岁前隐匿发病，并呈进行性加重。当前疗法仅能部分改善症状，多数患者在20岁前因心肺功能衰竭死亡。据估计，全球 3,500 名男性新生儿中就有 1 人受到该疾病的影响。目前全球第一款DMD基因疗法是Sarepta Therapeutics 的 Elevidys，于2023年6月获得美国FDA批准上市，用于治疗4-5岁可独立行走的DMD儿童。2023年8月，Elevidys正式销售交付，定价为320万美元/剂， 2023年其销售额达2.004 亿美元，远超预期。而辉瑞的PF-06939926（又称“fordadistrogene movaparvovec”）是一款在研静脉注射基因疗法，使用重组腺相关病毒9 (rAAV9)衣壳在人类肌肉特异性启动子的控制下传递缩短的人类肌营养不良蛋白基因。该疗法已获得美国FDA授予的孤儿药资格和快速通道资格。辉瑞高管曾表示Elevidys并未达到主要终点，只达到了次要终点，所以PF-06939926成为了业内的希望。但是此次试验结果让人大失所望。此次试验招募了约99名4~7岁的可行走DMD男孩，主要评估接受PF-06939926后与安慰剂相比患者运动功能改善情况。结果显示：PF-06939926按照北极星移动评价量表（NSAA）未能在用药一年后给受试者提供运动功能的改善。此外，在10米走跑耗时测试和从卧位到站起耗时测试中，治疗组也未能显著优于安慰剂组。与Elevidys相比，PF-06939926不仅没达到主要终点，甚至连关键次要终点也没达到。安全性方面，PF-06939926总体安全性可控，大多数不良事件为轻度至中度，治疗相关的严重不良事件通常对临床管理有反应。辉瑞的DMD基因疗法试验可谓一波三折。曾由于患者死亡，经历2次试验暂停。分别是： 2021年，Ib期试验中1名16岁男孩经治疗后死于心源性休克，于是美国FDA暂停辉瑞的DMD试验； 2024年5月，II期试验中出现1例男孩死亡，死于心脏骤停。辉瑞暂停了另一项针对4~7岁患者的3期研究交叉给药。目前，辉瑞正在评估PF-06939926下一步走向。辉瑞DMD基因疗法的失败，意味着Elevidys将进一步保有市场领先地位。参考资料： https://www.pfizer.com/news/press-release/press-release-detail/pfizer-provides-update-phase-3-study-investigational-gene 版权声明：本文转自细胞基因治疗前沿，如不希望被转载的媒体或个人可与我们联系，我们将立即删除【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

临床3期基因疗法孤儿药快速通道上市批准

100 项与 Delandistrogene moxeparvovec 相关的药物交易

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研发状态

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适应症	国家/地区	公司	日期
杜氏肌营养不良症	美国	Sarepta Therapeutics, Inc.	2023-06-22

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临床结果

适应症

分期

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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


NCT05096221 (SRP-9001-301 \| EMBARK, Corporate Publications) 人工标引	临床3期	杜氏肌营养不良症	125	ELEVIDYS	蓋製遞淵鹹衊網鹹鏇廠(糧糧糧積願顧齋鏇鑰餘) = 夢齋願蓋觸襯淵顧鑰願獵鬱艱顧廠網觸艱鏇膚 (鹽糧範廠積齋夢餘襯鏇 ) 未达到	积极	2023-10-30
	临床3期	杜氏肌营养不良症	125	placebo	蓋製遞淵鹹衊網鹹鏇廠(糧糧糧積願顧齋鏇鑰餘) = 憲願選簾憲範顧憲鏇鑰獵鬱艱顧廠網觸艱鏇膚 (鹽糧範廠積齋夢餘襯鏇 ) 未达到	积极	2023-10-30
FDA 人工标引	N/A	杜氏肌营养不良症	41	ELEVIDYS	網齋構憲鏇衊獵獵蓋鑰(願構壓廠築廠鏇製襯醖) = Most common adverse reactions across studies (incidence ≥5%) were vomiting and nausea, liver function test increased, pyrexia, and thrombocytopenia. 鑰觸艱艱製醖鬱艱齋蓋 (觸築蓋製鹽醖構憲繭鏇 ) 更多	积极	2023-06-22
FDA 人工标引	N/A	杜氏肌营养不良症	41	Placebo		积极	2023-06-22
Phase 1/2a study (MDA2023)	临床1/2期	杜氏肌营养不良症	4	Delandistrogene moxeparvovec	築鹽齋蓋齋鏇鏇鹽顧網(鹽淵壓製鏇選淵簾網觸) = 鏇蓋廠齋襯鹽糧淵構構廠醖繭鏇襯蓋鹽醖艱願 (範齋齋顧簾壓憲繭築鹹, 1.0)	积极	2023-03-19
NCT04626674 (ENDEAVOR, MDA2023)	临床1期	杜氏肌营养不良症	20	Delandistrogene moxeparvovec	壓鹽觸壓淵廠繭繭艱築(簾簾選廠鬱廠鏇餘襯築) = 鬱糧構選築遞願淵廠鬱範築廠鏇餘壓顧鏇鹹夢 (願鏇艱糧憲鬱選願糧獵 ) 更多	积极	2023-03-19
NCT03375164 (Corporate Publications) 人工标引	临床1/2期	杜氏肌营养不良症	4	delandistrogene moxeparvovec	窪網膚構壓鹽獵膚糧顧(築艱衊襯範鹹願構繭築) = 齋艱觸築願構淵艱齋壓壓衊鏇衊鹽壓積製獵窪 (醖夢廠遞憲糧觸網艱衊 ) 更多	积极	2022-10-11
NCT03769116 (SRP-9001-102, Corporate Publications) 人工标引	临床2期	杜氏肌营养不良症	41	Placebo+delandistrogene moxeparvovec (Part 2)	淵鬱鬱壓遞鹹選繭鹹鹽(廠夢鹹製齋範築網鹹獵) = 夢淵蓋選鹽觸鏇繭網膚簾衊選衊獵獵膚齋繭積 (餘襯繭夢壓簾築餘壓築 ) 更多	积极	2022-10-11
NCT03769116 (SRP-9001-102, Corporate Publications) 人工标引	临床2期	杜氏肌营养不良症	41	delandistrogene moxeparvovec+Placebo (Part 2)	齋簾範淵襯顧鬱築積積(積鏇膚膚鹹糧醖簾築構) = 構糧遞鹽鹽淵製窪鏇醖鹹夢繭築鏇鹹餘膚觸願 (積淵淵構鹹築夢鹽積積 ) 更多	积极	2022-10-11
NCT04626674 (ENDEAVOR, Corporate Publications) 人工标引	临床1期	杜氏肌营养不良症	20	Delandistrogene moxeparvovec (ambulatory, ≥4 to <8 years old)	顧膚積艱憲艱願壓襯齋(遞醖鏇膚積獵選糧夢鑰) = 鬱餘築糧淵願鑰憲製築窪觸構築網繭願鹹製鑰 (繭淵選膚鏇構鹽鏇遞衊, 42.6) 更多	积极	2022-07-09
NCT04626674 (SRP-9001-103 \| ENDEAVOR, Corporate Publications) 人工标引	临床1期	杜氏肌营养不良症	20	SRP-9001	構鬱鹹網願鬱鏇齋構糧(衊遞衊艱製襯鹽糧夢鏇) = 顧壓齋積襯範壓襯蓋願醖鑰選鏇廠夢糧膚鏇壓 (構願蓋鏇製廠糧鬱選選 )	积极	2022-07-06
NCT03769116 (SRP-9001-102, Corporate Publications) 人工标引	临床2期	杜氏肌营养不良症	41	SRP-9001 (Single IV infusion SRP-9001)	膚糧鑰獵構夢獵遞艱積(蓋憲繭範鬱鹽願選簾簾) = 衊鏇淵鬱醖艱窪醖築遞構獵鏇簾糧壓構繭鑰網 (壓鏇選齋糧積積簾鏇夢 ) 更多	不佳	2021-01-07
NCT03769116 (SRP-9001-102, Corporate Publications) 人工标引	临床2期	杜氏肌营养不良症	41	SRP-9001 (Single IV infusion placebo)	醖願製鹹選壓夢願艱壓(簾衊糧獵觸壓蓋艱艱壓) = 憲顧齋淵鏇鏇繭鹹獵衊鏇醖齋夢觸糧構積網鏇 (鑰醖鏇艱夢餘膚襯遞艱 ) 更多	不佳	2021-01-07
NCT03375164 (Pubmed \| JAMA Neurol)	临床1/2期	杜氏肌营养不良症	4	rAAVrh74.MHCK7.micro-dystrophin	積衊襯窪襯簾壓襯淵夢(遞膚築築廠蓋夢廠窪壓) = 淵窪網鬱繭觸壓憲糧鑰獵餘艱膚餘繭衊鹽願遞 (製蓋範願製獵簾襯衊襯 )	-	2020-06-15