This Monday, March 29th, Wave Life Sciences shared a press release and community letter explaining that data from their PRECISION-HD1 and PRECISION-HD2 trials does not support further development of the huntingtin-lowering ASOs they were testing in people. Essentially, these relatively small trials were designed to measure whether two genetic drugs could lower the harmful form of huntingtin in the spinal fluid of people with HD. The bottom line: despite being safe and well tolerated, neither drug successfully lowered huntingtin, so they will not be useful treatments for HD.
This outcome has absolutely nothing to do with last week’s announcement from Roche. The data from the PRECISION-HD trials was expected from Wave by the end of Q1 2021, and they delivered. Though we were all hoping for a better outcome, the research community will learn from this roadblock, and in fact, Wave will soon be moving forward with a third ASO trial to lower mutant huntingtin. This new drug, called WVE-003, has an updated chemical structure so there is hope that it will have more potent effects in people. For a more in-depth discussion of the news, check out the most recent HDBuzz article.
News about Dosing Halt for GENERATION-HD1: Resources Recap
If you missed them, here are some resources to learn more about what the news from Roche means for the HD community, as well as how to support ourselves and our loved ones as we move forward together.
HDSA webinar/Q&A about processing the news, and answering scientific questions using the information available.
A video message from Roche to the community.
HDBuzz article about the Roche news.
We also received some new information this week about when more data is expected to be shared with the community. From Roche:
- We understand the HD community wants more information about the reasons for this decision, and at Roche/Genentech we are working with urgency to access and understand the data. We now have the raw data from GENERATION HD1 and are in the process of analysing this.
- The full analysis of GENERATION HD1 will take time, and we plan to share data and learnings with the community over the course of the year. As a first step, we will present preliminary data from GENERATION HD1 to the community at CHDI at the end of April.
HD research forges ahead: many sources of optimism
After the challenges brought forth in recent weeks, HDSA remains optimistic that the demonstrated commitment of pharmaceutical leaders to the HD community will continue to progress us towards new treatments for HD. Even in the wake of the ASO trial news, we continue to hear from companies entering the HD space and seeking to incorporate family voices into drug development.
Prilenia Therapeutics is running the PROOF-HD clinical trial to test pridopidine as a treatment for early HD, and new site locations are being added on a weekly basis on the Huntington Study Group website and at www.hdtrialfinder.org. They also launched a website which reviews previous studies of pridopidine in HD and provides resources to learn more about the ongoing Phase 3 trial.
Anima Biotech, a leader in the discovery of small molecule drugs that can control expression of individual genes, has teamed up with Takeda in a preclinical research collaboration that will expand upon Anima’s existing Huntington Disease program aimed at selectively lowering mutant huntingtin. Should they find preclinical success, the partners will work to expand the molecules to clinical candidates, which Takeda will look to develop and commercialize.
Vaccinex, which announced last year that the SIGNAL trial of pepinemab for Huntington’s disease unfortunately did not meet its key goals, shared its 2020 Fourth Quarter Update. Despite failing to reach its primary endpoints in the trial, after fully analyzing the data Vaccinex believes that pepinemab could still have potential cognitive benefit for HD patients. They are currently exploring the possibility of moving into phase 3 in individuals with mid-stage HD symptoms.