The following is a community letter from Wave Life Sciences about their SELECT-HD trial. To learn more about allele-selectivity, check out our Breaking Down Barriers video.

Dear Members of the Huntington’s Disease Community,

Today we announced positive results from SELECT-HD, our Phase 1b/2a placebo-controlled trial evaluating the investigational therapy WVE-003. These results demonstrate that WVE-003 selectively lowers toxic, mutant huntingtin (mHTT) protein and preserves healthy, wild-type huntingtin (wtHTT) protein for individuals with Huntington’s disease.

Read the complete press release

Trial Results In our analysis, we compared participants treated with three 30 mg intrathecal doses of WVE-003 every 8 weeks to participants who received placebo and saw the following:

• Significant, durable mHTT lowering of up to 46%.

• Preservation of healthy, wtHTT.

• WVE-003 was generally safe and well-tolerated.

• Statistically significant correlation of mHTT lowering with slowing of caudate loss, which is an imaging biomarker that is predictive of clinical outcomes.

• While this study was not powered for clinical outcomes, slowing of decline was observed for Total Motor Score (TMS).

What happens next? Based on the successful SELECT-HD study, next steps for WVE-003 will be informed by meetings with regulators to discuss the development path for WVE-003, which will include a potential for accelerated approval as well as an open-label extension (OLE) study for SELECT-HD.

Our gratitude All of us at Wave would like to extend our deepest thanks to the clinical trial participants, their families, investigators, and clinical site staff who have dedicated their time and effort to SELECT-HD. Your continued contributions are critical to advancing the discovery and development of new treatments for HD, which we hope will help improve the lives of people impacted by HD.

We look forward to sharing future updates on our WVE-003 program. If you have any questions, please reach out to our advocacy team at patientadvocacy@wavelifesci.com.

Sincerely, Chelley Casey VP Patient Advocacy