Wave Life Sciences said new Phase 2 biomarker data for its exon-skipping therapy are promising for certain patients with Duchenne muscular dystrophy, and it plans to discuss accelerated approval plans with the FDA early next year.
The company on Tuesday disclosed the results, which come at the 24-week halfway point of the study that is testing WVE-N531 administered every two weeks in 11 boys with DMD who are amenable to exon 53 skipping. Ten of the boys are ambulatory, meaning they can still walk on their own, and one is non-ambulatory.
Wave reported biomarker data from nine of the ambulatory boys, and chief development officer Anne-Marie Li-Kwai-Cheung told investors on Tuesday that the company did not have biomarker results from one boy, since his muscle biopsy was “too low-quality to be analyzed.”
Wave found that muscle content-adjusted dystrophin levels were 9% of normal and average unadjusted dystrophin expression was 5.5% of normal. The biotech also said that eight of nine ambulatory boys reached muscle content-adjusted dystrophin levels that were at least 5% of normal, a sign that the boys were able to produce more of the key muscle protein.
“Achieving 9% dystrophin and doing that consistently, I think, is a really transformational dataset for the field, which is so used to low inconsistent levels of dystrophin from study after study,” CEO Paul Bolno said in an interview before the news was announced. Wave’s shares $WVE jumped about 45% Tuesday morning.
Anne-Marie Li-Kwai-CheungThe company noted that its data showed WVE-N531 could enter muscle stem cells, which Li-Kwai-Cheung said hasn’t been reported before with the approved gene therapy or approved exon skipping drugs to her knowledge.
There are currently two approved exon 53 skipping therapies on the market — Sarepta Therapeutics’ Vyondys 53 and NS Pharma’s Viltepso. (In June, Sarepta also won a controversial broad approval of its Duchenne muscular dystrophy gene therapy.) For both exon skipping therapies, patients are dosed once a week while Wave’s experimental therapy is dosed once every two weeks in this study. The company plans to switch the enrolled boys to a once-monthly dosing regimen, citing the drug’s 61-day half-life.
There were four cases of mild treatment-related adverse events reported in three boys, with no serious side effects and no study discontinuations. Li-Kwai-Cheung told investors that the treatment displayed “an extraordinarily clean profile for an exon-skipping therapy.”
The company didn’t share data on functional improvements, though it expects to have final 48-week data in the first quarter of 2025. It plans to engage US regulators then to discuss the accelerated approval pathway.
Bolno told investors that the company is also assessing another endpoint called stride velocity 95th centile (SV95C), a digital measure of a patient’s fastest strides over a 180-hour period. European regulators have emphasized this measure more than their US counterparts as a secondary endpoint for DMD studies.
“The fact that we’ll be generating these data will be important as we do think about treatment opportunities for boys not just in the US, but outside the US,” he said.
Editor’s note: This story was corrected to note that four cases of adverse events were treatment-related in three boys.