Wave, with new data, plots path forward for Huntington’s drug

 

• Wave Life Sciences on Tuesday said it will meet with regulators to discuss what kind of evidence would be needed to support an accelerated approval application for an experimental drug it’s developing for Huntington’s disease.

• The biotechnology company shared its plans alongside results from a placebo-controlled clinical trial testing the drug, dubbed WVE-003. Data showed treatment significantly lowered levels of a mutant protein that causes the neuron death behind Huntington’s. Wave also said this mutant protein lowering correlated with slowing of “caudate atrophy,” a biomarker the company says is predictive of clinical outcomes.

• “[W]e have been working diligently to establish caudate volume as a biomarker for clinical development,” said Anne-Marie Li-Kwai-Cheung, Wave’s chief development officer, in a statement. “We believe these strong data compel a case for accelerated approval for WVE-003, which we plan to discuss with regulators.”

WVE-003 is Wave’s second attempt at designing an effective drug for Huntington’s, after the company in 2021 shelved two prior candidates that weren’t potent enough in testing. All three candidates are meant to silence expression of mutated forms of the “HTT” gene, thereby reducing levels of mutant “huntingtin” protein that’s toxic to neurons. (The resulting dysfunction and death of neurons is what causes the movement and thinking problems associated with Huntington’s.)

However, WVE-003 was designed using different chemistry modifications, and targets another nucleotide in the RNA transcript produced by mutant HTT. The idea is the drug will selectively degrade mutant HTT protein while sparing the wild-type HTT protein thought to be helpful to normal brain function.

The trial data Wave disclosed Tuesday are evidence of this desired “allele selectivity,” the company said. Participants in the study given three doses of WVE-003 had, on average, 46% lowering in mutant HTT protein levels in the cerebrospinal fluid, compared to placebo. Yet wild-type HTT protein levels were preserved and even increased, according to Wave.

“Wild-type huntingtin plays such a critical role in the central nervous system, and it’s very exciting to finally have an opportunity to evaluate mHTT lowering in the context of allele-selectivity and to see positive signals emerging,” Ralf Reilmann, founder of the George-Huntington Institute in Germany and lead investigator in Wave’s study, said in the company’s statement.

https://finance.yahoo.com/m/157b642c-29a5-3f32-bce5-2eb197786ffd/wave%2C-with-new-data%2C-plots.html