Wave Life Sciences Stock Plunges After Antisense Oligonucleotide Candidates Disappoint In Huntington's Disease Study

Wave Life Sciences Ltd's WVE closely-watched antisense oligonucleotide program crashed in an early-stage Huntington's disease study, thus wiping out two experimental drug candidates.

What Happened: WVE-120102 failed to separate from the placebo with no evidence of a dose-response on mutant Huntingtin protein (mHTT) at any of the doses.

WVE-120102 had a non-statistically significant median reduction of 9.9% in mHTT in the CSF compared to a pooled placebo group who had a median decrease in mHTT of 0.8%.

A separate, smaller open-label extension study showed modest reductions in mutant Huntingtin protein after a mean of 8.1 monthly doses, but effects were inconsistent over the trial. WVE-120101 had a non-statistically significant median reduction of 11.6% in mHTT in the CSF, versus 10.0%.

Wave will stop the clinical development of WVE-120102. The trial participants will have a final follow-up visit but receive no further doses.

The company will also stop the development of WVE-120101. Dosing in the 32 mg cohort of the PRECISION-HD1 core trial is complete, and core and OLE trial participants will have a final follow-up visit but receive no further doses.

The complete analysis of the 32 mg cohort is expected in the second quarter of this year. There are no observed changes in wtHTT and NfL during trials.

Why It Matters: Wave Life Sciences will now focus on the development of WVE-003 and WVE-004.

Site activation and enrollment in Phase 1b/2a trial of WVE-003 in Huntington's disease that carries SNP3 are currently underway. The dosing will start this year.

Wave also expects to initiate dosing in two other clinical trials this year, which will assess target engagement, impact on key disease biomarkers, and initial safety of WVE-004.

Also, last week Roche called off tominersen study targeting the huntingtin protein and a mutant variant.

Price Action: WVE shares dropped 18.9% at $5.75 in premarket trading on the last check Tuesday.