Paul BolnoPaul Bolno
Wave Life Sciences has announced that it will discontinue its development of suvodirsen, an investigational treatment for Duchenne muscular dystrophy (DMD) in patients with mutations amenable to exon 51 skipping after an interim analysis of an open-label extension study demonstrated no change from baseline in dystrophin expression with either the 3.5 mg/kg or 5 mg/kg doses of suvodirsen. The phase 2/3 DYSTANCE 51 trial (NCT03907072) will be discontinued in addition to the open-label extension.

The discontinuation comes less than a week after the FDA approved golodirsen (Vyondys 53; Sarepta) for the treatment of DMD with genetic mutations amenable to  exon 53 skipping. Investigators reported that patients experienced a significant increase in dystrophin production in skeletal muscle. Wave Life Sciences added that they will also be suspending their trial of WVE-N531, a drug aimed to treat patients with mutations amenable to exon 53 skipping.

“The suvodirsen results are unexpected and deeply disappointing to us, and undoubtedly will be to the patients we aim to serve. We are grateful to be part of the Duchenne community and our organization has been shaped by their strength and resilience,” said Paul Bolno, MD, CEO of Wave Life Sciences, in a statement. “While we did not achieve dystrophin restoration in this study, there is a rising tide in nucleic acid therapeutics, and we are fully committed to advancing genetic medicines in diseases of the central nervous system, eye, and liver.”

The multicenter, phase 1, open-label extension of suvodirsen included 36 patients who were randomly assigned to doses of either 3.5 mg/kg or 5 mg/kg. Deltoid biopsy was required prior to the initial dosing. Due to the trial cut-off for the interim analysis, only 27 of 36 patients had a follow-up biopsy. Among those in the 5 mg group, 10 and 9 patients received a follow-up muscle biopsy at 12 and 22 weeks, respectively, while 8 patients in the 3.5 mg/kg group had a follow-up biopsy at 22 weeks.  

Patients are expected to have 1 final follow-up visit, but no further doses will be administered and no muscle biopsies will be conducted.

Notably, the FDA recently authorized the first newborn screening test for DMD, giving laboratories the ability to add the GSP Neonatal Creatine Kinase-MM kit to their newborn screening panels. The Muscular Dystrophy Association requested DMD to be added to the Recommended Uniform Screening Panel (RUSP) because of the high amount of cases that result from maternal carriers of dystrophin mutations. While this move by the FDA is not a recommendation that the screening test be added to the RUSP, it is a solid step in that direction.
REFERENCE
Wave life sciences announces discontinuation of suvodirsen development for Duchenne muscular dystrophy [news release]. Cambridge, MA. Wave Life Sciences. December 16, 2019. globenewswire.com/news-release/2019/12/16/1960830/0/en/Wave-Life-Sciences-Announces-Discontinuation-of-Suvodirsen-Development-for-Duchenne-Muscular-Dystrophy.html. Accessed December 16, 2019.