New Medicines

Vyondys 53Duchenne muscular dystrophy in patients who have genetic mutations subject to skipping exon 53 of the DMD gene


Vyondys 53
New molecular entity
Sarepta Therapeutics
Sarepta Therapeutics

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Apr 22It appears Roche has yet to exercise its option to commercialise golodirsen outside the US. Sarepta has not announced any specific plans to seek a licence for golodirsen in the EU or UK. Availability in the UK in the near future seems very unlikely [15,16].
Dec 21No plans for filing in EU or UK described on company website [13,14].
Sep 20Sarepta have granted Roche an exclusive option to obtain an exclusive license to commercialise certain products, including golodirsen, outside of the U.S. If this option is exercised, Roche will have sole control over and decision-making authority with respect to the commercialisation of such products outside the U.S. [11].
Jan 20PIII ESSENCE (NCT02500381) trial estimated primary completion date is May 2022 [9].
Dec 19Launched in the US [10].
Dec 19FDA grants accelerated approval to Vyondys 53 (golodirsen) injection to treat DMD patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping [8].
Dec 19Sarepta said it intends to file for approval of golodirsen to treat in pts who have genetic mutations subject to skipping exon 53 of the DMD gene. They hope to receive accelerated approvalprior to completion of the PIII ESSENCE trial. They anticipates filing for approval of golodirsen by the end of the year.[4]
Aug 19The FDA rejected the New Drug Application for golodirsen for DMD. The decision was made due to risk of infection linked to i.v. infusion ports placed under the skin to administer the drug as well as kidney toxicity seen in animal studies. The company plans to request a meeting with the FDA to discuss its next steps. [7]
Dec 18Sarepta completes submission of its New Drug Application (NDA) to the FDA seeking approval of golodirsen (SRP-4053) in patients with Duchenne muscular dystrophy amenable to skipping exon 53 [5].


Genetic transcription inhibitor of dystrophin gene. Golodirsen allows exon 53 to be skipped, providing altered messenger RNA (mRNA) with a shortened but functional version of dystrophin. [2,4]
In the UK, about 100 boys are born with Duchenne MD each year, and there are about 2,500 boys living with the condition in the UK at any one time.[1]
Duchenne muscular dystrophy in patients who have genetic mutations subject to skipping exon 53 of the DMD gene
Intravenous infusion

Trial or other data

Nov 18: ESSENCE study estimated primary completion now May 2022 [6].

Feb 18: ESSENCE trial on temporary hold following one serious adverse event (SAE) that could possibly be related to the investigational drug product. The study remains blinded and the adverse event observed is consistent with those seen in pts with DMD. The safety data were reviewed by an independent Data Monitoring Committee (DMC). The DMC deemed that dosing could continue for all patients. However, the MHRA required that dosing stop at all UK sites. Sarepta is currently submitting an amendment to the MHRA. Following approval from the MHRA, dosing can be reinitiated at the UK sites.[3]

Sep 17: Positive results from the phase I/II (4053-101; EudraCT2014-002008-25; NCT02310906) trial reported. Mean dystrophin protein increased to 1.019% of normal compared to a mean baseline of 0.095% of normal (p < 0.001) as measured by Western blot, the primary biological endpoint in the study - a 10.7 fold increase from baseline. Further, the study showed a statistically significant increase in dystrophin immunofluorescence as measured by immunohistochemistry (IHC), confirming sarcolemma-associated protein expression and distribution. The two-parts trial randomised 12 patients in part 1 and 13 patients in part 2 to receive a dose titration of golodirsen or placebo.[2]

Aug 16: PIII, randomised, double-blind, parallel-assignment ESSENCE trial (4045-301; NCT02500381) initiated. This will evaluate the efficacy and safety of golodiresen vs. placebo, in pts aged 7-13 yrs with Duchenne muscular dystrophy (DMD) with deletions amenable to skipping exon 45 and exon 53, respectively. Pts will be randomised to receive once weekly IV infusions of 30 mg/kg SRP-4045 or 30 mg/kg golodiresen respectively or placebo for up to 96 weeks, followed by an open label extension period, where all patients will receive open-label SRP-4045 or golodirsen for up to 96 weeks. The primary endpoint was defined as change in 6 minute walk test (6MWT) from baseline to week 96. The trial intends to enrol 99 pts in the US, Belgium, Canada, France, Germany, Italy, Netherlands, Sweden and the UK.[2]

Dec 14: Initiation of a randomised, double-blind, placebo-controlled dose escalation PI/II trial to evaluate the pharmacokinetics, safety and tolerability of golodiresen in ~48 pts aged 6-15 with DMD, responsive to exon 53 skipping (4053-101; EudraCT2014-002008-25; NCT02310906). Enrolment underway in France, the UK and Italy.[2]