Genentech expects to start enrolling study participants early next year.
The GENERATION HD2 study will evaluate the safety, biomarkers, and efficacy of investigational drug tominersen in people aged 25 to 50 with prodromal (very early subtle signs of HD) or early manifest HD. This global study plans to enroll approximately 360 participants in 15 countries.
This will be a randomized, placebo-controlled study, where eligible participants will receive one of two doses of tominersen (60mg or 100mg) or a placebo every 4 months via a lumbar puncture. The study will be double-blinded, meaning neither the participant nor the study team will know whether the participant is receiving tominersen or a placebo. The study will conclude after all participants have completed 16 months of treatment. An independent data monitoring committee (iDMC) will monitor the trial and will review safety, clinical, and biomarker data every 4-6 months.
What is the basis of the new Phase II GENERATION HD2 study?
Tominersen is an investigational drug that has been studied in several clinical trials since 2015, including in a Phase III study called GENERATION HD1 that tested two different dose regimens of tominersen in adults with manifest HD (120mg every 2 months, and 120mg every 4 months). This is a higher dose than what will be used in the upcoming GENERATION HD2 study.
The GENERATION HD1 study did not meet its main objectives. Dosing of tominersen was stopped in the GENERATION HD1 study in March 2021 after the iDMC evaluated the overall benefits and risks of tominersen in study participants.
However, after Phase III data were available to Roche, exploratory analyses suggest that lower exposure to tominersen may benefit younger adult patients with earlier stages of HD. It is important to note that findings from these exploratory analyses were not statistically significant (i.e., clearly different) versus placebo and could represent a chance result, so they are not definitive and need to be confirmed. Therefore the new Phase II GENERATION HD2 study aims to assess lower doses of tominersen in an earlier HD population than those involved in the previous study.
HD research is cumulative - thank you to all participants in previous studies
All other tominersen studies closed this summer, and Genentech wants to thank all study participants and families who supported the previous studies again. These studies comprised the first-ever Phase III clinical program to test the huntingtin-lowering hypothesis. Additionally, it was because of the HD community’s commitment to research that the trials recruited faster than expected, and thus generated data faster than anticipated.
The incredible HD community inspires all researchers to continue pursuing potential options for people impacted by the disease. Regardless of a study’s outcome, the journey of tominersen research is an example of how every clinical study adds to the overall body of research knowledge. Every piece of data collected is vital. Even if we learn something may not work, or may work differently than thought, together as a research community we get one step closer to finding out what may work for people with HD. And this research can only be done with the participation of the HD community.