RegulationPriority Review (US), Fast Track (US), Accelerated Approval (US), Orphan Drug (US), Rare Pediatric Disease (US), Orphan Drug (EU), Orphan Drug (JP), Paediatric investigation plan (EU)

Gene Sequence

Sequence Code 453698636

Clinical Trials associated with Delandistrogene moxeparvovec

NCT06270719 / RecruitingNot Applicable

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.

Start Date07 Feb 2024

Sponsor / Collaborator

Sarepta Therapeutics, Inc.

NCT06241950 / Active, not recruitingPhase 1

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.

Start Date29 Jan 2024

Sponsor / Collaborator

Sarepta Therapeutics, Inc.

[+1]

NCT06128564 / RecruitingPhase 2

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.

Start Date29 Nov 2023

Sponsor / Collaborator

Hoffmann-La Roche Ltd.

[+1]

100 Clinical Results associated with Delandistrogene moxeparvovec

100 Translational Medicine associated with Delandistrogene moxeparvovec

100 Patents (Medical) associated with Delandistrogene moxeparvovec

Literatures (Medical) associated with Delandistrogene moxeparvovec

01 Apr 2024·Pediatric neurology

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

Article

Author: Mendell, Jerry R ; Darton, Eddie ; McDonald, Craig M ; Mason, Stefanie ; Murphy, Alexander P ; Muntoni, Francesco ; Mercuri, Eugenio ; Proud, Crystal ; Zaidman, Craig M ; 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.

01 Jan 2024·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

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

31 Dec 2023·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

Author: 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.

146

News (Medical) associated with Delandistrogene moxeparvovec

17 Jun 2024

·www.prnewswire.com

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

Phase 3Drug ApprovalOrphan DrugFast Track

17 Jun 2024

·www.biospace.com

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.

Phase 3Clinical ResultDrug ApprovalPhase 2Priority Review

13 Jun 2024

·www.biopharmadive.com

Pfizer setback brings questions for Duchenne gene therapy ahead of Sarepta decision

The failure of a Pfizer medicine for Duchenne muscular dystrophy adds new uncertainty around the effectiveness of gene therapy for the muscle-wasting condition, days before the Food and Drug Administration is expected to decide on expanding use of a similar treatment from Sarepta Therapeutics.On Wednesday, Pfizer said the treatment missed its mark in a definitive Phase 3 study of boys between 4 and 7 years of age with Duchenne. Pfizer didnt disclose specifics, but said the therapy didnt lead to a significant difference versus placebo on a measure of motor function, or on key secondary measures such as timed tests for how quickly study participants could stand or walk. The results will be presented at future medical and patient advocacy meetings.The studys failure makes it much less likely there will soon be a second gene therapy option for people with Duchenne, a progressive and deadly condition with no cure and limited treatment options. Pfizer had previously expected to file for a regulatory approval of its medicine if study results were positive. Now the company says it is evaluating appropriate next steps for the program. Multiple Wall Street analysts expect Pfizer to discontinue research.The results are a discouraging blow to our community, particularly devastating to those who participated in the study, said Parent Project Muscular Dystrophy, a patient advocacy group, in a statement.The setback also has important implications for Sarepta, whose therapy, Elevidys, is the only approved gene therapy for the disease. The Food and Drug Administration is currently reviewing whether to broaden use of Elevidys. A decision is expected by June 21.The FDA last year granted an accelerated approval to Elevidys, a milestone clearance built on decades of scientific research into how to correct the genetic errors that cause Duchenne. Yet that approval was narrower than Sarepta had hoped, a reflection of mixed study results that led some FDA scientists to question Elevidys effectiveness. The therapy was only approved after Peter Marks, the head of the FDA office that reviews gene therapies, overruled other agency reviewers.Pfizer and Sareptas treatments deliver into the body instructions to make a tiny version of a muscle-protecting protein that people with Duchenne lack. Researchers engineered this so-called microdystrophin because its small enough to pack into the benign viruses used to deliver gene therapies. It is designed to imitate a form of the protein found in people with a milder type of muscular dystrophy.The FDA has established dystrophin production as a biological marker likely to predict a benefit in Duchenne patients, and has used it to approve multiple therapies in the last decade. Developers and researchers similarly believe microdystrophin can be helpful, and that the substantial levels gene therapies produce can halt or even reverse Duchennes course.But evidence in testing of Sarepta and Pfizers therapies hasnt shown that, leading to uncertainty about the connection between protein production and functional benefits. Sareptas treatment missed the main goal of two placebo-controlled trials, one of which was meant to provide confirmatory evidence for Elevidys approval. A dystrophin-boosting medicine from Japanese drug developer Nippon Shinyaku also recently failed a trial that was supposed to validate earlier results. Now Pfizers therapy has fallen short, too.The findings could perpetuate some questions about correlation between micro/mini-dystrophin expression and functional improvements, which could be important for the FDAs comfort around accelerated approval for Elevidys in broader populations, wrote RBC Capital Markets analyst Brian Abrahams in a note to clients.Having a second gene therapy with a relatively similar approach show efficacy could have helped reassure that Elevidys's effects are real [or] replicable, Abrahams added.Baird analyst Brian Skorney noted how skeptics believe the stumbles for dystrophin and microdystrophin-producing drugs should lead to the agency rethinking the suitability of the proteins as predictive markers.Sarepta has argued the totality of the evidence in its clinical trials makes clear the benefits of treatment. Unlike Pfizer, Sarepta reported consistent benefits on multiple secondary measures in its latest trial effects that, it claims, persuaded the FDA to consider a broader label. Sareptas treatment is also made of different gene therapy components and testing hasnt been slowed by safety concerns, as Pfizers therapy has.As a result, analysts have expected the FDA to widen Elevidys availability, and many still do following Pfizers setback. Skorney contended, that rather than change its view of Elevidys, the agency and companies should re-evaluate the viability of designing Duchenne trials with one-year study goals. Because Duchenne is a heterogeneous condition, that just isnt enough time to detect a treatment effect, he wrote.In a separate note to clients, Mizuho Securities Uy Ear wrote the FDA has likely already made its decision, rendering Pfizer's results irrelevant to Sareptas case.The consistency of Pfizers negative data provide support for Sarepta's consistently positive secondary results, according to Ear, who added that his team believes “the key secondary endpoints demonstrate that Elevidys has activity in [Duchenne] and that these positive data were unlikely to be a coincidence.“ '

Phase 3Gene Therapy

100 Deals associated with Delandistrogene moxeparvovec

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Muscular Dystrophy, Duchenne	US	Sarepta Therapeutics, Inc.	22 Jun 2023

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05096221 (SRP-9001-301 \| EMBARK, Corporate Publications) Manual	Phase 3	Muscular Dystrophy, Duchenne	125	ELEVIDYS	inebifwtmd(jnsgmznchp) = atkrtsmrpr oiipyypvgj (fsqndxriof ) Not Met	Positive	30 Oct 2023
	Phase 3	Muscular Dystrophy, Duchenne	125	placebo	inebifwtmd(jnsgmznchp) = uzesyenrmr oiipyypvgj (fsqndxriof ) Not Met	Positive	30 Oct 2023
FDA Manual	Not Applicable	Muscular Dystrophy, Duchenne	41	ELEVIDYS	bmxsymnqcp(ioyzkjgbsy) = Most common adverse reactions across studies (incidence ≥5%) were vomiting and nausea, liver function test increased, pyrexia, and thrombocytopenia. aysdhnkquy (kvzzrufxtj ) View more	Positive	22 Jun 2023
FDA Manual	Not Applicable	Muscular Dystrophy, Duchenne	41	Placebo		Positive	22 Jun 2023
Phase 1/2a study (MDA2023)	Phase 1/2	Muscular Dystrophy, Duchenne	4	Delandistrogene moxeparvovec	rsikumvypo(ajlzxclzjt) = gnuwgkpuvv tryzrxfztu (cqpxkmhafp, 1.0)	Positive	19 Mar 2023
NCT04626674 (ENDEAVOR, MDA2023)	Phase 1	Muscular Dystrophy, Duchenne	20	Delandistrogene moxeparvovec	atesvpiuzz(elvtqrsyry) = zbvoxhnpxp jssvnzruqm (ujcudycygu ) View more	Positive	19 Mar 2023
NCT03769116 (SRP-9001-102, Corporate Publications) Manual	Phase 2	Muscular Dystrophy, Duchenne	41	Placebo+delandistrogene moxeparvovec (Part 2)	kviklzjxcv(znxtwfjlte) = yymrqkoxcs esvbagavti (dwkdrjvoun ) View more	Positive	11 Oct 2022
NCT03769116 (SRP-9001-102, Corporate Publications) Manual	Phase 2	Muscular Dystrophy, Duchenne	41	delandistrogene moxeparvovec+Placebo (Part 2)	czdxguzwwe(ffrtbecler) = zyfpxzhhxc qoqxpdzlib (ejeylbbkax ) View more	Positive	11 Oct 2022
NCT03375164 (Corporate Publications) Manual	Phase 1/2	Muscular Dystrophy, Duchenne	4	delandistrogene moxeparvovec	dluqfcsoad(owddolnbjw) = ixyatmkuek iaqkyvurvk (zmlaqudmtp ) View more	Positive	11 Oct 2022
NCT04626674 (ENDEAVOR, Corporate Publications) Manual	Phase 1	Muscular Dystrophy, Duchenne	20	Delandistrogene moxeparvovec (ambulatory, ≥4 to <8 years old)	jpckjgqmxx(zdbxrpkjqo) = buyhibfaof tpqlgjrggy (tzfjfddcks, 42.6) View more	Positive	09 Jul 2022
NCT04626674 (SRP-9001-103 \| ENDEAVOR, Corporate Publications) Manual	Phase 1	Muscular Dystrophy, Duchenne	20	SRP-9001	gnagkxcqgy(outyzmhydv) = tlcmysohad nnxxzyhqbr (qivvkkuads )	Positive	06 Jul 2022
NCT03769116 (SRP-9001-102, Corporate Publications) Manual	Phase 2	Muscular Dystrophy, Duchenne	41	SRP-9001 (Single IV infusion SRP-9001)	ufjcnbcube(ymirdnggyp) = ideixybpzl wokblajkou (qunaitfczt ) View more	Negative	07 Jan 2021
NCT03769116 (SRP-9001-102, Corporate Publications) Manual	Phase 2	Muscular Dystrophy, Duchenne	41	SRP-9001 (Single IV infusion placebo)	kkgyjazacv(llrthmzqea) = yoteukxica deaetlqipp (kjhnjcjyel ) View more	Negative	07 Jan 2021
NCT03375164 (Pubmed \| JAMA Neurol)	Phase 1/2	Muscular Dystrophy, Duchenne	4	rAAVrh74.MHCK7.micro-dystrophin	aylncumdhl(fmrdwhyjjh) = uczzngtodz hnnmbpxvuz (lsfygiopzj )	-	15 Jun 2020

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