Wave ALS Update Delights Industry Observers, Investors

ALS Concept

Researchers in WAVE Life Sciences' Phase Ib/IIa study on a potential treatment for amyotrophic lateral sclerosis (ALS) shared a positive update on the drug's disease-targeting abilities.

The ongoing FOCUS-C9 trial showed that WVE-004, the clinical candidate for C9-ALS and frontotemporal dementia (C9-FTD), remained effective across the various dose levels tested. Participants received 10 mg, 30 mg and 60 mg doses for around three months and demonstrated clinically significant reductions in poly(GP) numbers. After single 30 mg doses were given, patients experienced a 34% drop in poly(GP) on the 85th day.

The company's shares rose by 29.6% on NASDAQ shortly after the announcement.

FOCUS-C9 is an adaptive study designed to determine the dose level and frequency of WVE-004 based on early engagement indicators. The latest update is based mainly on observations of poly(GP) dipeptide repeat proteins found in the cerebrospinal fluid. Poly(GP) is a key biomarker of C9-ALS and C9-FTD. When it is at lower levels in the CSF, this means that WVE-004 is engaging with the disease target in the spinal cord and the brain.

"While early, these data are encouraging and open an opportunity to target the disease at the RNA level. It is encouraging to see the benefits of the study's adaptive design, where this early analysis has already helped narrow the doses being explored and enabled more precise, real-time exploration of dose response and optimization," commented Merit Cudkowicz, M.D., chief of the neurology department and director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital and chairperson for the trial's clinical advisory committee. 

A multidose cohort focusing on giving patients 10 mg per month is in the works. More single and multidose data are also expected to be shared throughout 2022. Wave is hoping that more positive results come in to enable discussions with regulatory authorities about its next development plans.

"Based on our preclinical PK/PD modeling, we expected that relatively low doses would engage [the] target; however, seeing this level of poly(GP) knockdown three months after a single 30 mg dose exceeded our expectations and we expect poly(GP) to reduce further with repeat administrations. The next step is to identify a regimen that maximizes knockdown with repeat dosing, while potentially enabling quarterly or less frequent dosing," added Michael Panzara, M.D., MPH, the chief medical officer and head of Wave's therapeutics discovery and development unit in the same announcement.

In addition to WVE-004, Wave is pushing forward with two PhaseIb/IIa clinical trials on WVE-003 and WVE-N531 in 2022. WVE-003 is a drug that targets SNP3 in Huntington's disease and will be evaluated in the SELECT-HD study, while WVE-N531 targets exon 53 in Duchenne muscular dystrophy. The company is also working on advancing its alpha-1 antitrypsin deficiency program, which uses its novel GalNAc-conjugated A-to-I(G) RNA base editing oligonucleotides. Wave expects to begin studies in the third quarter of 2022.

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