- Wave Life Sciences, a biotech based in Cambridge, Massachusetts, is shelving its two most advanced drugs after early clinical testing found neither had a large enough effect on the mutated proteins that cause Huntington's disease.
- The tests evaluated five doses of Wave's drugs, known as WVE-120101 and WVE-120102. High-level results announced Monday show the drugs did not perform significantly better than placebo, nor was there any evidence the dose levels affected how patients responded to treatment. While an extension study of WVE-120102 did see "modest reductions" in the disease-causing proteins, Wave said these effects were "inconsistent over the course of the trial."
- As Wave winds down its two lead programs, the company is hoping another of its experimental drugs will fare better. The drug, called WVE-003, has a different chemical backbone than its predecessors, which Wave believes will allow it to target a specific mutation in the gene responsible for making huntingtin protein. The company expects to begin dosing patients in an early-stage study of WVE-003 sometime this year.
In designing its drugs, Wave takes short pieces of genetic material called oligonucleotides and chemically modifies them to block the production of harmful proteins.
The approach isn't new, though Wave claims to put its own spin on it. Researchers have been exploring the therapeutic potential of oligonucleotides for decades, and in recent years have watched that work turn into approved treatments for several inherited, often debilitating diseases.
But the victories haven't come without setbacks. Ionis Pharmaceuticals, one of the pioneers in the field, has built a lengthy list of partners but breaking through with approved drugs has been a longer road. Another leading company, Sarepta, has three oligonucleotide drugs on the market, but questions remain about how helpful they actually are to patients. And just last week, the Swiss pharmaceutical giant Roche gave a disappointing update to a Huntington's drug it's developing with Ionis.
Wave has run into its own share of problems, announcing in late 2019, for example, that it would stop development of an experimental treatment for Duchenne muscular dystrophy after an early-stage clinical trial generated negative results.
Now, Wave is discontinuing two more programs, leaving it with only a preclinical pipeline.
"This is not where we hoped to be today. What makes it even more difficult for us is that it's on the heels of another devastating setback for the patient community," Michael Panzara, Wave's chief medical officer, said on a Monday call with investors, referring to the recent Roche and Ionis news.
Huntington's disease is a neurodegenerative illness caused by defects in the gene that makes the huntingtin protein. Because typical, so-called "wild" huntingtin performs a variety of important functions, drug developers like Wave are trying to create therapies that only block the mutated forms.
Wave's first drugs didn't appear to have this desired effect based on the newly available clinical results. But the company is optimistic that WVE-003, which is made using a different chemistry approach, will be better. It's designed to lower mutant huntingtin by going after a single DNA change that's often seen in mutated huntingtin genes.
"Today, all of our clinical preclinical and discovery pipeline programs are supported by this next-generation chemistry," said Paul Bolno, Wave's CEO.
Wave expects to offer patients from the WVE-120101 and WVE-120102 studies the ability to participate in the WVE-003 trial slated to begin this year. The company says an estimated 40% or so of adults with Huntington's carry the single DNA change that WVE-003 targets.
Wave investors don't appear sold on this strategy just yet, though, as the company's share price was down about 30% late Tuesday morning.
Since coming to the public market in 2015, Wave shares have gone from $16 apiece, to more than $50 apiece in early 2018, to just over $5 as of Tuesday.
Note: This story has been updated to better describe Ionis Pharmaceuticals' partnership history.