Wave’s Huntington’s Drug Disappoints in Clinical Trial, Stock Sinks

Wave Life Sciences’ stock took another plunge after the company reported early results from its Huntington’s disease study.

Cambridge, MA-based Wave Life Sciences (NASDAQ: [[ticker:WVE]]) earlier this week released topline data from its ongoing Phase 1b/2a PRECISION-HD2 trial evaluating WVE-120102.

The experimental therapy is being developed for the potential treatment of Huntington’s disease (HD), a neurological disorder in which the brain’s nerve cells gradually deteriorate, causing a breakdown in a patient’s ability to think and move. The disease is ultimately fatal.

The Wave drug, WVE-120102, was designed to lower mutant huntingtin protein by targeting single nucleotide polymorphism (SNP) rs362331 (SNP2). While the preliminary analysis showed a “statistically significant” reduction in the mutant form of the protein compared to placebo, the company says there was no reduction in total huntingtin protein levels.

Additionally, the analysis reviewed the presence of neurofilament light chain (NfL) in the cerebrospinal fluid, levels of which are often elevated when neurons are damaged. According to the company, the NfL levels were the same in both the WVE-120102 and placebo-treated groups.

Following the announcement, the company’s stock fell nearly 37 percent from $15.8 on December 27 to $9.34 Monday morning. At close on New Year’s Eve the stock was priced at $8.02. It is currently trading at $7.60.

The stock plunge is the second for the company in the last month. In mid-December,  Wave announced its decision to discontinue development of its investigational Duchenne muscular dystrophy drug, suvodirsen, after data showed the treatment wasn’t working.

In an investor note, SVB Leerink analysts noted the “lower than expected” mutant huntingtin knockdown falls short of RG6042—a comparable treatment in development by Ionis Pharmaceuticals (NASDAQ: [[ticker:IONS]]) and Roche. Due to the disappointing results, the analysts reduced their probability of success for the Wave Huntington’s program from 50 percent to 30percent.

Still, WVE-120102 was generally well tolerated so the company says it will add a higher dose cohort this month and expects to release additional data in the second half of 2020.

Approximately 30,000 people in the US have symptomatic HD and more than 200,000 are at risk of inheriting the disease based on their genetics.

There is no known cure and no disease-modifying therapies are currently approved, though several companies are developing potential drugs. Triplet Therapeutics out of Cambridge, MA, joined Ionis and Roche in pursuit of a Huntington’s treatment. The startup—which in December closed a $49 million Series A round—is taking a different approach to HD drug research, by targeting DNA damage responses.

Voyager Therapeutics (NASDAQ: VYGR) and uniQure (NASDAQ: QURE) also are developing gene therapies to treat the disease.

(Photo by Robina Weermeijer on Unsplash)