Wave Life Sciences achieves first human RNA editing in AATD trial

Wave Life Sciences has achieved a groundbreaking milestone in the field of therapeutic RNA editing with its RestorAATion-2 trial, targeting alpha-1 antitrypsin deficiency (AATD). This genetic disorder is known to affect the lungs and liver. The trial marks the first instance of RNA editing being used as a treatment in humans.

In this phase 1b/2a study, participants received a single subcutaneous dose of WVE-006. The results were promising, as the therapy led to a significant restoration of wild-type M-AAT protein levels in two patients who have the "ZZ" genotype, which is a serious form of AATD. The restored protein constituted over 60% of the total alpha-1 antitrypsin (AAT) observed, and the effectiveness of the treatment was detectable up to 57 days after administration.

The trial's data revealed that the plasma levels of total AAT reached about 11 micromolar, with the mean wild-type M-AAT making up more than 60% of the total AAT. These findings are significant because they indicate that RNA editing has the potential to restore protein levels to those similar to the "MZ" genotype. Individuals with the "MZ" genotype have a lower likelihood of developing severe lung and liver diseases related to AATD.

The ongoing trial aims to gather more data, and Wave Life Sciences intends to release information from a multidose cohort in 2025. The initial results have laid a solid foundation for the continued exploration of RNA editing as a therapeutic approach for AATD.

Importantly, WVE-006 was well tolerated by patients. All reported adverse events were mild to moderate, and no serious adverse events were observed. This safety profile is encouraging for the future development of this treatment.

Wave Life Sciences retains the exclusive rights to develop and commercialize WVE-006. However, an agreement is in place with GSK, granting them the responsibility to further develop and commercialize the treatment after the RestorAATion-2 study is completed. According to this agreement, Wave Life Sciences could potentially earn up to $525 million in milestone payments as well as royalties on the net sales of the treatment.

This breakthrough in RNA editing therapy offers hope for individuals suffering from AATD. The significant restoration of functional protein levels suggests a promising future for this innovative treatment approach, potentially transforming the standard of care for this genetic disorder. Wave Life Sciences' ongoing research and collaboration with GSK highlight the commitment to advancing this therapy towards broader clinical use, aiming to improve the lives of patients affected by AATD.