GSK has decided to return rights to WVE-006, an RNA editing oligonucleotide developed by Wave Life Sciences for alpha-1 antitrypsin deficiency (AATD), leaving the Massachusetts-based biotech with full control over the program. The company did not provide a specific reason for the decision, which follows the release of Phase Ib/IIa clinical data in September 2025 that came in below analyst expectations.
The September data showed that patients treated with repeat injections of a 200-mg dose of WVE-006 achieved 11.9 micromolar of alpha-1 antitrypsin (AAT) protein. At the time, Wave described the result as therapeutically relevant. However, Truist Securities analysts said they had expected AAT levels of 12 micromolar or higher, noting that the outcome was “exceedingly close” but still below buy-side expectations.
Despite this, the analysts maintained a positive outlook on higher doses. Truist said a 400-mg dose “could drive total AAT well into the 13uM+ range.” Data from that dose are expected in the first quarter of 2026, while results from a 600-mg single dose and from multidose cohorts are expected later this year, according to a Monday news release. Truist also noted that GSK’s decision to step away ahead of these readouts means there should be no read-through to upcoming AATD data.
Wave said GSK had been expected to take over development of WVE-006 once the current Phase 1b/2a RestorAATion-2 trial concluded. Instead, Wave now plans to continue development independently and seek accelerated approval for the candidate from the U.S. Food and Drug Administration. Data from RestorAATion-2 are expected in the first quarter of this year, and the company expects regulatory feedback by mid-2026.
“We have been eager to accelerate our registrational strategy for WVE-006 since reporting our interim data that achieved key AATD treatment goals,” Wave CEO Paul Bolno, M.D., said in the announcement.
AATD is caused by a defective SERPINA1 gene, leading to insufficient production of AAT, a protein that protects lung tissue. Low AAT levels can result in emphysema, while abnormal accumulation of the protein in the liver can lead to cirrhosis over time. Unlike gene-editing approaches aimed at permanently correcting the SERPINA1 gene, Wave’s strategy focuses on transiently correcting the mRNA produced by the gene.
Although GSK has stepped away from WVE-006, the broader collaboration between the companies remains in place. The partnership began in December 2022, when GSK paid $170 million upfront and committed up to $3.3 billion in potential milestones for an exclusive global license to WVE-006 and access to Wave’s PRISM platform, which supports RNA silencing and editing programs. Under the agreement, GSK planned to advance up to eight preclinical programs.
According to Wave, GSK selected a fourth program to advance last month, with validation work ongoing across several therapeutic areas. If these programs proceed, Wave could receive up to $2.8 billion in additional milestones, along with tiered royalties.
Wave reported $196.2 million in cash and equivalents as of Sept. 30, 2025, and said its current cash runway is expected to fund operations into the third quarter of 2028, excluding any potential milestone payments.
GSK Hands Back WVE-006 Rights to Wave After AATD Results
GSK has returned the rights to WVE-006 — an investigational RNA editing therapy it was jointly developing for alpha-1 antitrypsin deficiency (AATD) — back to Wave Life Sciences. The decision follows early Phase Ib/IIa clinical results that fell below broader expectations, prompting GSK to realign its strategic focus away from the rare disease program.
What Happened With WVE-006 and GSK
Under the original collaboration, GSK held an exclusive global license to develop and commercialize WVE-006 while supporting Wave’s ongoing RestorAATion-2 clinical trial. After reviewing data from the Phase Ib/IIa study, the companies agreed that Wave Life Sciences is better positioned to take full control of WVE-006 and advance its regulatory strategy independently.
Clinical Readouts and Strategic Implications
The mid-stage readout showed that WVE-006 was able to raise key markers of alpha-1 antitrypsin protein but did not fully meet the more optimistic expectations of some analysts. As a result, GSK decided not to continue with the AATD program, returning rights to Wave while maintaining collaboration on other RNA-based programs.
