Wave Life Sciences Achieves First Human RNA Editing, Advances Pipeline
Key Insights
Wave Life Sciences reported the first-ever RNA editing in humans with WVE-006 for alpha-1 antitrypsin deficiency (search) (AATD), showing increased wild-type AAT protein levels.
Clinical trial for WVE-007, a GalNAc-siRNA targeting INHBE for obesity (search) treatment, is on track for Q1 2025, with potential for monotherapy or combination with GLP-1s.
FDA provides supportive initial feedback on WVE-003 for Huntington’s disease (search), open to caudate atrophy as a biomarker for accelerated approval; IND submission expected in 2H 2025.
Wave Life Sciences has announced significant progress in its RNA medicine pipeline, including the achievement of first-in-human RNA editing and advancements in programs targeting obesity (search), Huntington's disease (HD), and Duchenne muscular dystrophy (search) (DMD). The company's third-quarter financial results and business update highlight key clinical milestones and strategic developments.
RNA Editing Breakthrough in Alpha-1 Antitrypsin Deficiency
The RestorAATion-2 trial of WVE-006, a GalNAc-conjugated AIMer, has demonstrated the first-ever RNA editing in humans. This therapy targets alpha-1 antitrypsin deficiency (search) (AATD), a genetic disorder affecting the lungs and liver. Data from the first single-dose cohort showed that circulating wild-type M-AAT protein in plasma reached a mean of 6.9 micromolar at day 15, representing more than 60% of total AAT. Mean total AAT protein increased from below the level of quantification at baseline to 10.8 micromolar at day 15, meeting the level that has been the basis for regulatory approval for AAT augmentation therapies. WVE-006 was well-tolerated with a favorable safety profile across both RestorAATion-1 and RestorAATion-2. Multidose data from RestorAATion-2 is expected in 2025.
Advancing Obesity Treatment with WVE-007
Wave Life Sciences is developing WVE-007, a GalNAc-conjugated siRNA targeting INHBE, as a novel approach to treat obesity (search). Preclinical data suggests WVE-007 has the potential to be used as a monotherapy, as an add-on to GLP-1s for further improvement of weight loss or to reduce the doses of GLP-1s, and for maintenance to prevent weight regain and weight cycling after discontinuing GLP-1s. A clinical trial for WVE-007 is on track for initiation in the first quarter of 2025.
Huntington's Disease Program Receives Positive FDA Feedback
WVE-003, an allele-selective oligonucleotide for Huntington’s disease (search) (HD), has received supportive initial feedback from the FDA. The FDA is engaged in discussing pathways to accelerated approval and open to Wave’s plan to evaluate biomarkers, including caudate atrophy, as an endpoint to evaluate HD progression. An Investigational New Drug (IND) application for WVE-003 is expected in the second half of 2025. SELECT-HD clinical trial results demonstrated allele-selective reductions in CSF mutant huntingtin (mHTT) protein and preservation of healthy, wild-type huntingtin (wtHTT) protein with multiple doses of WVE-003, as well as a statistically significant correlation between mHTT reductions and slowing of caudate atrophy.
Progress in Duchenne Muscular Dystrophy with WVE-N531
Positive interim data from the FORWARD-53 study of WVE-N531, an exon skipping oligonucleotide for Duchenne muscular dystrophy (search) (DMD), were announced. The interim analysis, conducted after 24 weeks of 10 mg/kg dosing every two weeks, showed a mean absolute muscle content-adjusted dystrophin (search) expression of 9.0% (range: 4.6-13.9%) as measured by Western Blot. 89% of ambulatory participants achieved muscle content-adjusted dystrophin levels of at least 5%. Mean exon skipping was 57% (range: 31-75%) as measured by RT-PCR. The company expects to deliver the complete 48-week FORWARD-53 data and receive feedback from regulators on a pathway to accelerated approval in the first quarter of 2025.
Financial Position
Wave Life Sciences reported cash and cash equivalents of $310.9 million as of September 30, 2024, with a cash runway expected into 2027.