Approval Probability
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Label indication VYONDYS 53 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VYONDYS 53 [see Clinical Studies ( 14 )] . FDA label
Also known as Golodirsen, VYONDYS 53
SRP-4053 · 1 trial · 1 indication
Adverse event (AE) was any untoward medical occurrence in a clinical trial participant, which does not necessarily have a causal relationship with the investigational drug. A Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; Required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as AEs that were reported or worsened on or after the start of study drug dosing through 12 weeks. TEAEs included both Serious TEAEs and non-serious TEAEs.
Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal finding were reported as TEAEs. The Investigator determined whether abnormal assessment results were potentially clinically significant or not. Potentially clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were potentially clinically significant or not. Potential clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Physical examinations were performed by the Investigator, or qualified study staff. A full physical examination included a review of general appearance, head, eyes, ears, nose and throat, heart, lungs, abdomen, extremities, skin, lymph nodes, musculoskeletal, and neurological systems. Number of participants with potentially clinically significant abnormalities in physical examinations were reported. Potentially clinically significant abnormalities in physical examinations were based on Investigator's discretion.
Twelve-lead ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel. Number of participants with potentially clinically significant abnormalities in ECG reported as TEAEs presented here. The Investigator determined whether abnormal assessment results were potentially clinically significant or not.
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with potentially clinically significant abnormalities in ECHO were reported.
6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course of 25 meters for 6 minutes (timed), and the distance walked (in meters) was recorded. Change from baseline in 6MWT distance at Week 144 in total golodirsen group was reported.
6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course of 25 meters for 6 minutes (timed), and the distance walked (in meters) was recorded. Change from baseline in 6MWT distance at Week 144 in untreated group (non-exon 53 amenable participants) was calculated.
Change from baseline in dystrophin protein levels (in muscle biopsy samples) was determined by Western blot in total golodirsen group.
| Arm | Type | Description |
|---|---|---|
| Part 1: SRP-4053 | EXPERIMENTAL | Patients will receive SRP-4053 (golodirsen) intravenous (IV) infusions, weekly, at escalating dose levels as follows: Weeks 1-2, 4 mg/kg/week; Weeks 3-4, 10 mg/kg/week; Weeks 5-6, 20 mg/kg/week; Weeks 7-12, 30 mg/kg/week. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator. |
| Part 1: Placebo | PLACEBO_COMPARATOR | Patients will receive SRP-4053 placebo-matching IV infusions, weekly, for 12 weeks. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator. |
| Part 2: SRP-4053 | EXPERIMENTAL | All eligible patients from Part 1, as well as new patients, will receive SRP-4053 (golodirsen) 30 mg/kg/week IV infusions, weekly, for up to 168 weeks. |
| Part 2: Untreated Group | NO_INTERVENTION | Patients with DMD who have a genotypically confirmed deletion of exon(s) not amenable to treatment by exon 53 skipping, but who otherwise meet the same eligibility criteria as treated patients newly recruited to Part 2, will undergo the same study assessments as treated Patients (except for pharmacokinetic \[PK\] sampling and muscle biopsies), but at a reduced schedule through Week 144. The untreated patients are not considered as control group. |
| Name | Type | Description |
|---|---|---|
| Placebo | DRUG | SRP-4053 placebo-matching solution for IV infusion. |
| SRP-4053 | DRUG | SRP-4053 (golodirsen) solution for IV infusion. |
Inclusion Criteria: * Diagnosed with DMD, genotypically confirmed. * Intact right and left biceps muscles or an alternative upper arm muscle group. * Stable pulmonary and cardiac function. * Minimum performance on 6MWT, North Star Ambulatory Assessment, and rise (Gowers) test as specified in the st...
SRP-4053 is an investigational small molecule developed by Sarepta Therapeutics for Duchenne Muscular Dystrophy. It is designed to target exon 53 of the dystrophin gene transcript. It has completed a Phase 1 clinical trial and is not approved for commercial use.
SRP-4053 is being developed for the treatment of Duchenne Muscular Dystrophy, a genetic muscle-wasting disorder. The Phase 1 study enrolled male patients aged 6 years and older with DMD. It is an investigational therapy and has not been approved for any indication.
SRP-4053 targets exon 53 of the dystrophin gene transcript. By acting on this RNA target, the small molecule is intended to address the underlying genetic defect in Duchenne Muscular Dystrophy. The trial was biomarker-selected, meaning patients were chosen based on relevant genetic characteristics.
SRP-4053 is being developed by Sarepta Therapeutics, Inc., which trades on the Nasdaq under the ticker SRPT. Sarepta is a biopharmaceutical company focused on genetic medicines, including treatments for Duchenne Muscular Dystrophy.
SRP-4053 has completed a Phase 1 clinical trial and remains investigational. It is not FDA approved. The single completed study, NCT02310906, was a Phase I/II trial that enrolled 39 patients across the United States, France, Italy, and the United Kingdom.
SRP-4053 has been studied in one completed clinical trial, NCT02310906, titled Phase I/II Study of SRP-4053 in DMD Patients. The trial was randomized, double-blind, and placebo-controlled, enrolling 39 male participants aged 6 years and older with Duchenne Muscular Dystrophy.