Wave tanks again as Huntington's clinical trial data underwhelm

Data from a phase 1b/2a trial have raised doubts about whether Wave Life Sciences’ Huntington’s disease drug can compete with Roche and Ionis’ rival candidate. The results wiped 50% off Wave’s share price, adding to losses it suffered when it dumped a Duchenne muscular dystrophy (DMD) program earlier in December. 

Wave’s Huntington’s asset, WVE-120102, is an antisense oligonucleotide designed to stop the body from making a mutant huntingtin protein linked to the disease. Roche and its partner Ionis also have an experimental asset designed to reduce production of the protein.

Data on Roche and Ionis’ asset, RG6042, set the bar Wave needed to clear to show WVE-120102 is a viable contender for the Huntington’s market. Wave’s phase 1b/2a trial failed to clear that bar.

The trial linked WVE-120102 to a 12.4% placebo-adjusted reduction in mutant huntingtin protein. That result was statistically significant but compares unfavorably to data on RG6042, which drove a 40% reduction in the mutant protein in a phase 1/2 trial. The unfavorable comparison shaped analyst impressions of the results.  

“In its first human data for Huntington's disease, an encouraging efficacy signal (albeit underwhelming; lower vs competitor) and dose-dependent response imply that the set higher dose could offer improvement,” analysts at Jefferies wrote in a note to investors.

Wave put a positive spin on the results, talking up the prospects of a higher dose delivering greater efficacy. To test that hypothesis, Wave plans to add a 32 mg dose cohort to the trial this month. The data shared to date cover patients treated with doses up to 16 mg. Wave’s willingness to add a higher dose cohort reflects the generally favorable safety and tolerability profile seen to date. 

Strong data from the 32 mg cohort could put Wave back in contention in the race for the Huntington’s market, but, as it stands, the odds are stacked against it. Roche and Ionis have a more advanced asset that, on the basis of available data, looks to more efficacious than Wave’s WVE-120102. Those facts led investors to drive Wave’s share price down 50% after seeing the Huntington’s data. 

Back-to-back data drops have radically revised assessments of Wave’s prospects. Ahead of the DMD readout last month, Wave shares traded above $37. The DMD flop drove Wave’s share price down to $16, only for the Huntington’s data to send it spiraling downward again toward $8.