Wave culls leading Huntington's meds as shares go under after rival Roche hit by similar fate

Wave Life Sciences
Paul Bolno, M.D., president and CEO of Wave (Wave Life Sciences)

Just over a year after Wave Life Sciences cut staffers, threw out a Duchenne muscular dystrophy med and saw its Huntington's disease drug flop in a key test, the waves come crashing down again for the biotech.

In an update posted after-hours Monday evening, Wave said data out of a midstage tests for two of its Huntington’s drugs, WVE-120102 and WVE-120101, were simply too poor to keep going, and they have been axed.

WVE-120102 works as an antisense oligonucleotide designed to stop the body from making a mutant huntingtin (mHTT) protein linked to the disease. The writing was already on the wall for the experimental drug after it failed to beat or match Roche and Ionis’ rival Huntington’s med tominersen.

RELATED: Wave tanks again as Huntington's clinical trial data underwhelm

WVE-120101, meanwhile, also works as an antisense oligonucleotide and interferes with the mutant mRNA copy of the huntingtin (HTT) gene. It does this by binding to the mutant mRNA, preventing the cell’s protein-making machinery from reading it. This prevents abnormal Huntingtin protein from being produced.

Across two trials, however, the drugs failed to perform. In the so-called PRECISION-HD2 core trial, results from all participants (88 in total) showed “no statistically significant change” in mHTT when pitted against a dummy treatment, either with single or multiple doses of WVE-120102.

In an open-label test, too, the data were poor and “inconsistent,” the biotech said. A similar testing theory was also behind its other asset WVE-120101, and, because of the failure seen for the former drug, the biotech is also cutting its losses here.

“Given these and results from Wave’s previous clinical trials, as well as current understanding of the limitations of the company’s first-generation candidates, Wave will also stop clinical development of WVE-120101,” the company said in a statement.

This is a notoriously tough area: Huntingdon’s disease has few success stories in R&D and is a tricky target. Just ask Roche and Ionis, which earlier this month stopped work on tominersen, also known as IONIS-HTTRx and RG6042, which is designed to reduce production of HTT.

This was the very drug Wave lost out to last year, but a lack of efficacy appears to have scuppered the pair’s blockbuster hopes.

RELATED: Roche halts Huntington's phase 3 of Ionis-partnered antisense drug as blockbuster hopes fade

Wave will, however, continue on with a third asset, which it sees as a next-generation drug, in WVE-003, which is designed to selectively lower mHTT by targeting a specific single nucleotide polymorphism (SNP3).

The biotech is planning dosing in a phase 1b/2a this year and will offer some trial subjects from its failed test that may have this biomarker for “potential enrollment in the WVE-003 trial.” Wave said 40% of adults with the disease carry SNP3 in association with the Huntington’s mutation, so there could be some crossover.

“Everyone at Wave wishes our PRECISION-HD programs had yielded different results, but we believe our WVE-003 program will enable us to address deficiencies with our first-generation candidates while maintaining our commitment to developing wild-type sparing therapies for HD,” said Paul Bolno, M.D., president and CEO of Wave.

“Our next generation of investigational clinical candidates, which also includes WVE-004 for amyotrophic lateral sclerosis and frontotemporal dementia and WVE-N531 for Duchenne, as well as our current preclinical and discovery programs, all use novel PN chemistry, which has been shown to increase potency, exposure, and durability across our silencing, splicing, and editing modalities in preclinical studies.

“Moreover, we are implementing innovative, adaptive designs across our new clinical programs to speed development and help us make data-driven decisions more quickly. These collective advances and learnings will improve our ability to deliver transformative genetic medicines.”

Despite the upbeat mantra, shares in Wave crashed Monday night, down 15% premarket on the news.

Analysts at Jefferies said that in light of Roche’s flop, expectations for Wave’s efforts were “low,” but added: “Not even showing biomarker reduction at higher dose is a surprise.”

After its Duchenne cull more than a year ago and now the axing of its two Huntington’s meds, Jefferies sees  “little room for optimism.”