Golodirsen
- Generic Name
- Golodirsen
- Brand Names
- Vyondys 53
- Drug Type
- Biotech
- CAS Number
- 1422959-91-8
- Unique Ingredient Identifier
- 033072U4MZ
- Background
Golodirsen is a morpholino antisense oligomer designed to treat about 8% of patients with Duchenne Muscular Dystrophy (DMD). This is an X-linked condition leading to progressive muscle degeneration that begins in early childhood, rendering many patients wheelchair-bound by age 12. Often, patients succumb to this condition by age 30 or younger due to cardiac and respiratory complications. A similar drug used in the treatment of other types of DMD is eteplirsen, which targets a different genetic mutation.
Golodirsen was developed by Sarepta Therapeutics and granted accelerated FDA approval on December 12, 2019 due to the urgent need for this drug in patients suffering from a certain form of DMD. Continued approval of this drug will depend on the results of clinical trials that confirm its clinical benefit. Golodirsen was initially rejected for FDA approval over concerns about its potential renal toxicity, however, clinical trials did not show significant toxicity.
- Indication
Golodirsen is indicated to treat Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene that would benefit from exon 53 skipping. Continued FDA approval of this drug is contingent upon the results of clinical trials to confirm its benefit.
- Associated Conditions
- Duchenne Muscular Dystrophy (DMD)
Wave Life Sciences to Seek FDA Approval for Duchenne Muscular Dystrophy Drug Following Promising Phase 2 Results
• Wave Life Sciences will pursue FDA accelerated approval for WVE-N531, an exon 53 skipping therapy for Duchenne muscular dystrophy, following positive Phase 2 trial results showing increased dystrophin production.
• The experimental treatment demonstrated substantial improvements in muscle health with a statistically significant improvement in "time to rise" functional tests compared to historical controls through 48 weeks of treatment.
• If approved, WVE-N531 could offer a potential monthly dosing regimen and become a new therapeutic option for approximately 8-10% of Duchenne patients with specific genetic mutations amenable to exon 53 skipping.
Nippon Shinyaku’s DMD Drug Fails Confirmatory Trial
Nippon Shinyaku's Duchenne muscular dystrophy (DMD) therapy, Viltepso, has failed a confirmatory clinical trial, casting doubt on its future. The drug, designed for DMD patients with specific genetic mutations, did not show a significant difference from placebo in improving the time taken for patients to stand up from a lying position.
Sarepta Seeks Accelerated Approval for DMD Gene Therapy SRP-9001
• Sarepta Therapeutics has submitted SRP-9001 (delandistrogene moxeparvovec) to the FDA for accelerated approval to treat ambulatory Duchenne muscular dystrophy (DMD) patients.
• The filing is based on positive data from early-stage studies, showing improvements in clinical function and a consistent safety profile, while awaiting Phase 3 EMBARK results.
• SRP-9001, a one-time gene therapy, delivers a shortened dystrophin gene via an AAV vector, addressing the underlying genetic defect in DMD patients.
• If approved, SRP-9001 would offer a one-time treatment option for DMD, contrasting with Sarepta's existing chronic exon-skipping therapies.
Capricor Therapeutics Completes FDA Submission for Deramiocel in DMD Cardiomyopathy
• Capricor Therapeutics has completed its Biologics License Application (BLA) submission to the FDA for deramiocel to treat Duchenne muscular dystrophy (DMD) cardiomyopathy.
• The BLA is supported by data from Phase 2 HOPE-2 and HOPE-2 Open Label Extension (OLE) trials, showing attenuation of cardiac implications of DMD.
• The FDA has been requested to grant priority review, potentially reducing the review period to six months from the standard ten months.
• The BLA submission triggers a $10 million milestone payment to Capricor from its distribution partner, Nippon Shinyaku.
Elevidys Gene Therapy Shows Sustained Benefits in Duchenne Muscular Dystrophy Patients
• Sarepta Therapeutics' Elevidys demonstrates sustained benefits and disease stabilization in ambulatory Duchenne muscular dystrophy (DMD) patients, according to Phase 3 EMBARK trial results.
• Crossover-treated patients showed a 2.34-point improvement on the North Star Ambulatory Assessment (NSAA) compared to matched external controls after 52 weeks of Elevidys treatment.
• Patients treated with Elevidys in Part 1 of EMBARK maintained clinically meaningful improvements in NSAA, Time to Rise (TTR), and 10-meter walk/run (10MWR) at two years.
• Muscle biopsies showed consistent micro-dystrophin expression, and MRI scans indicated minimal muscle pathology progression, reinforcing Elevidys's long-term efficacy and safety.
Antisense Oligonucleotide Therapies Advance in Genetic Medicine
• Ionis Pharmaceuticals, a pioneer in antisense oligonucleotide (ASO) drugs, priced a $500 million IPO to fund clinical programs and commercial launches.
• Isarna Therapeutics' lead candidate, ISTH0036, targeting TGF-β, shows promise in Phase 2 trials for wet AMD and DME, major ophthalmic conditions.
• Regulus Therapeutics is advancing RGLS8429, an ASO targeting microRNA for autosomal dominant polycystic kidney disease (ADPKD), with positive Phase 1b data.
• Sarepta Therapeutics, with three approved PPMO therapies for Duchenne muscular dystrophy (DMD), continues to expand its RNA-based therapeutic pipeline.
Sarepta Discontinues Development of Vesleteplirsen for Duchenne Muscular Dystrophy
• Sarepta Therapeutics halts development of vesleteplirsen (SRP-5051), a more potent follow-up to Exondys 51 for Duchenne muscular dystrophy (DMD).
• The decision was influenced by risk-benefit considerations, FDA feedback, and the evolving DMD treatment landscape, including gene therapy options.
• Vesleteplirsen faced challenges, including a clinical hold by the FDA due to hypomagnesaemia observed in a clinical trial.
• Sarepta's revenues are shifting towards Elevidys, its gene therapy for DMD, which saw $181 million in sales compared to $249 million for exon-skipping drugs.
Sarepta Therapeutics Reports Strong Q3 2024 Financials and ELEVIDYS Expansion
• Sarepta Therapeutics reported a significant increase in total revenues for Q3 2024, reaching $1,243.6 million, up from $846.6 million in the same period last year.
• ELEVIDYS (delandistrogene moxeparvovec-rokl) received FDA approval for treating ambulatory Duchenne muscular dystrophy patients and expanded use to non-ambulatory patients.
• The company is advancing its manufacturing capabilities and expanding its product pipeline through strategic initiatives, including a new R&D facility and partnerships.
• Sarepta faces challenges including regulatory compliance, reimbursement uncertainties, and market acceptance of gene therapy, impacting its operational performance.
DMD Pipeline Shows Promise with Over 75 Therapies in Development
• Over 75 drugs are in development for Duchenne Muscular Dystrophy (DMD), targeting various mechanisms and routes of administration.
• REGENXBIO initiated a Phase I/II trial of RGX-202 in young boys with DMD to assess safety and efficacy.
• Emerging therapies focus on gene modulation, dystrophin replacement, and anti-inflammatory approaches to combat DMD.
• Key companies like Sarepta Therapeutics, Italfarmaco, and FibroGen are advancing DMD therapeutics through clinical trials.
Elevidys Gene Therapy for Duchenne Shows Sustained Benefit in Long-Term Follow-Up
• Five-year follow-up data from Study 101 supports the role of delandistrogene moxeparvovec (Elevidys) in stabilizing or slowing Duchenne muscular dystrophy (DMD) progression.
• Patients treated with Elevidys maintained 10-meter walk/run time over five years, showing a clinically meaningful difference compared to the external control cohort.
• EMBARK trial data indicates Elevidys does not negatively impact cardiac measures over a 52-week treatment period, reinforcing its manageable safety profile.
• A pre-specified global statistical test in the EMBARK trial indicated a functional treatment effect, despite not meeting the primary endpoint of change in NSAA score.
Pfizer's DMD Gene Therapy Fails to Meet Primary Endpoint in Phase III Trial
• Pfizer's fordadistrogene movaparvovec gene therapy for Duchenne muscular dystrophy (DMD) did not meet the primary endpoint in the Phase III CIFFREO study.
• The study, involving patients aged 4-8, assessed motor function improvement using the North Star Ambulatory Assessment (NSAA) scale after one year.
• Key secondary endpoints, including 10-meter run/walk velocity and time to rise from the floor, also showed no significant difference compared to placebo.
• Pfizer plans to share more detailed results from the CIFFREO study at an upcoming medical meeting.
Advancements in AAV Gene Therapy for Duchenne Muscular Dystrophy Show Promise
• AAV-mediated gene therapy is emerging as a promising strategy for treating Duchenne Muscular Dystrophy (DMD) by restoring dystrophin expression.
• Micro-dystrophin gene transfer using AAV vectors has demonstrated therapeutic success in large animal models, paving the way for human clinical trials.
• Clinical trials by Sarepta Therapeutics, Pfizer, and Solid Biosciences are underway, utilizing different mini-/micro-dystrophin constructs delivered via AAVs.
• Managing immune responses and optimizing vector dosage remain key challenges in achieving effective and long-term AAV gene therapy for DMD patients.
Biogen's Alzheimer's Drug in Spotlight Following Sarepta's Vyondys 53 Approval
The unexpected FDA approval of Sarepta Therapeutics' Vyondys 53 for Duchenne muscular dystrophy has sparked discussions about the potential flexibility the FDA might show towards Biogen's Alzheimer's drug, aducanumab. This comes amidst skepticism over the efficacy and safety of both drugs, with Biogen's application based on a controversial Phase 3 study.
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