- Wave Life Sciences on Dec. 30 said its experimental Huntington's disease drug significantly reduced levels of a damaging mutated protein across all doses tested so far. Wave expects to begin treating patients with an even higher dose this month.
- However, the 12% lowering in protein levels observed in Wave's study fell short of what was achieved by an experimental drug from Ionis Pharmaceuticals and Roche, which reduced protein levels by up to 42%.
- Wave shares fell by half to $7.99 apiece on Monday following the announcement of the trial results. Stifel analyst Paul Matteis wrote the results may raise questions about the company's drug development technology, since it also discontinued work on a Duchenne muscular dystrophy project in December.
December was a tough month for Cambridge, Massachusetts-based Wave, which dropped out of the billion-dollar biopharma club after it scrapped two projects and reported disappointing data from a third. Shares have lost 78% of their value over the past month and were down 2% on Thursday.
The company aims to develop "stereopure" drugs that hit and correct gene targets more precisely than past technologies in the oligonucleotide space have done. Wave's ambition is to improve efficacy while reducing side effects.
But when Wave canceled suvodirsen and WVE-N531, which were intended to compete with Sarepta Therapeutics' Exondys 51 and Vyondys 53 in DMD, analysts raised questions on the company's platform. Such doubts could be heightened further by the Huntington's disease news.
With the Huntington's drug, the data was at least better than what the company reported in DMD.
Wave tested Huntington's patients at doses of 2, 4, 8 and 16 mg, and found an average reduction of mutant protein of 12.4% in cerebrospinal fluid across the 27 patients exposed to the drug at all doses when compared to placebo. Patients taking placebo saw their mutant protein levels rise 10%.
A further analysis revealed a statistically larger reduction in harmful protein at the 16 mg dose, but the company didn't disclose what the level was.
In addition, Wave said its drug had no effect on total huntingtin protein levels, which suggests the drug is not leading to a decrease in normal huntingtin protein, which plays an important although unclear role in neuronal health.
Mutant huntingtin protein disrupts the normal function of neurons, which is believed to result in the breakdown of nerve cells and the physical and cognitive decline in Huntington's disease patients.
Wave's drug reductions in mutant huntingtin protein were well short of that generated by Roche and Ionis' RG6042, which yielded decreases of 20%, 25%, 28%, 42% and 38% across five increasing doses. Patients taking placebo in that trial saw mutant huntingtin increase by a similar 10%.
Cantor Fitzgerald analyst Eliana Merle said the Wave data confirms RG6042 is in the lead as a treatment for Huntington's. Further competition still is emerging from UniQure with its gene replacement therapy AMT-130, for which human testing is about to begin.
Wave, meanwhile, is hoping to begin dosing patients at an even higher dose of 32 mg this month.
It also has a second experimental Huntington's disease drug that is in a Phase 1/2 trial evaluating dose levels of 2 mg to 16 mg. Based on the data revealed this week, Wave said it will add a 32 mg dose in that trial.