Wave Life Sciences won’t further develop one of its most advanced medicines, an experimental treatment for nerve disorders, after a key, early-stage clinical trial found it didn’t provide a substantial benefit to patients.
High-level results disclosed Tuesday show Wave’s medicine, named WVE-004, was generally safe and well tolerated. But after about six months of treatment, participants in the drug arm weren’t faring significantly better than those getting placebos.
The Wave team is “deeply disappointed that we were not able to see any evidence of potential benefits that would be expected to drive meaningful outcomes for these patients,” Paul Bolno, the company’s CEO, said in a statement. “Our hope is that these data can help advance future research, and we are committed to sharing results with the community at an upcoming medical congress.”
Wave’s study enrolled 35 people with either amyotrophic lateral sclerosis or frontotemporal dementia, two diseases in which nerve cells progressively degrade.
WVE-004, meanwhile, is what’s known as an “antisense” therapy, meaning it stops cells from turning genetic material into harmful or unwanted proteins. Wave specifically designed the drug to block mutant versions of “C9orf72,” a gene scientists have long associated with nerve-destroying disorders like ALS and FTD.
Wave said its drug does appear to be working as intended. The study found patients on WVE-004 had “robust, sustained reductions in poly(GP),” a protein that, according to some research, reflects the activity of mutant C9orf72.
“These data do reinforce that our preclinical data on target engagement and pharmacology are translating in the clinic,” Bolno said, adding that Wave is now more confident in its other drug programs targeting illnesses like Huntington’s disease and Duchenne muscular dystrophy.
However, the reductions seen in the WVE-004 trial didn’t improve patients’ function or stabilize their disease.
The study also explored whether Wave’s drug had an effect on another protein of interest to ALS researchers, “neurofilament light chain,” and got mixed results. The study evaluated three different doses of WVE-004 and found an undesirable outcome in two of those groups, with neurofilament light chain levels increasing in the fluid surrounding patients’ brains and spines.
Wave said its decision to end the WVE-004 program was based on the poly(GP) data and the “absence of biomarkers reasonably likely to predict clinical outcomes.”
Founded in 2012, Wave and its genetic medicine technology have attracted interest from both large pharmaceutical firms and public investors. The company raised $102 million through an initial public offering in 2015, and has counted Pfizer, Takeda Pharmaceutical and, more recently, GSK as partners.
Yet, Wave has also hit a string of research setbacks. In 2019, for instance, one of the company’s experimental therapies for Duchenne disappointed in an early-stage trial, leading its development to be discontinued.
A little over a year later, Wave shelved two drugs for Huntington’s after studies found them not significantly better than placebos.
The company’s stock has lost much of its value over the past five years, and currently trades at just under $4 per share.