Wave Life Sciences Ltd. announced its decision to discontinue development of suvodirsen for patients with Duchenne who have mutations amenable to exon 51 skipping, based on its interim analysis of the Phase 1 open-label extension (OLE) study. The results showed no change from baseline in dystrophin expression, as measured by western blot, with either the 3.5 mg/kg or 5 mg/kg doses of suvodirsen. No safety concerns or emerging safety signals were observed. In addition, Wave is suspending further development of WVE-N531, their candidate for individuals with Duchenne who have mutations amenable to exon 53 skipping.

We are all devastated by the news from Wave regarding the termination of this study. 2019 has been a difficult year, an emotional roller coaster – the highs of an approval just last week and then another blow with the termination of another study. For every step forward we see, it feels like we take one or two steps backward and struggle for answers.

In this case, there was no target engagement, no expression of dystrophin.  Wave has stated that as a result of this decision, they are working with clinical trial sites to immediately discontinue the OLE study and the Phase 2/3 trial, DYSTANCE 51. No further doses of suvodirsen will be administered, and no further biopsy procedures will be performed. They have indicated that they are also working with investigators to provide what they need to support families participating in these studies. After the final data from the study have been analyzed, Wave is committed to enabling investigators to share data for each patient with their family. PPMD will remain in contact with the Wave team and look forward to seeing this data so that we can better understand what happened in this trial.

As a community, we believe in antisense oligonucleotides as a strategy to express dystrophin by skipping or eliminating a single exon and restoring a truncated or shortened version of. We had high hopes that this stereopure oligo would become another option in the delivery of therapies for Duchenne.

Wave ensures us that they will continue to work hard to find answers – remember the definition of translational medicine, bench to bedside and often back to bench before returning to bedside. We are hopeful Wave will find a way forward and will return to the Duchenne community.

PPMD and World Duchenne Organization will host a webinar on Friday, December 20 with Wave to learn more. Details coming soon.

Read Wave’s Community Letter:

December 16, 2019

Dear Duchenne community:

We have a disappointing update to share on the clinical program for suvodirsen, our investigational
exon 51 skipping stereopure antisense oligonucleotide. After reviewing interim dystrophin results
from the Phase 1 open-label extension (OLE) study, we’ve made the difficult decision to discontinue
the suvodirsen program. In addition, we are suspending further development of our candidate for
individuals with Duchenne who have mutations amenable to exon 53 skipping.

We initiated our research in Duchenne with the goal of restoring meaningful levels of dystrophin and
we are profoundly saddened to have fallen short of achieving this objective with suvodirsen. Over
the past few years, as we’ve worked to develop suvodirsen, many of us at Wave have been privileged
to meet hundreds of families living with Duchenne, and to work with the advocacy organizations that
support you. The strength, courage, and perseverance of the Duchenne community has humbled and
inspired us every single day. While today’s announcement is deeply disappointing, we are hopeful
and confident that brighter days are ahead for individuals and families living with Duchenne.

The results from the clinical trial show that there was no change in dystrophin expression with either
the 3.5 mg/kg or 5 mg/kg doses of suvodirsen. These results were unexpected given the preclinical
results seen with suvodirsen, but clearly demonstrated that treatment with suvodirsen did not result
in increased dystrophin restoration in boys. No safety concerns were observed. We will share the
findings from this study in hopes that the community can benefit from its contributions to this
program.

As a result of this decision, we are working with clinical trial sites to immediately discontinue the OLE
study and the Phase 2/3 trial, DYSTANCE 51. No further doses of suvodirsen will be administered,
and no further biopsy procedures will be performed. We are also working with investigators to
provide what they need to support families participating in these studies. After the final data from
the study have been analyzed, we are committed to enabling investigators to share data for each
patient with their family.

Our sincere and heartfelt thanks to the individuals and families that have participated in clinical trials
for suvodirsen. If you or a family member are participating in the study, we encourage you to contact
your clinician for further information. We would also like to thank all of those in the Duchenne
community – including the families, advocacy partners, regulators, and clinicians – who have
provided invaluable guidance on this program.

Sincerely,
Paul Bolno
President and Chief Executive Officer

 

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