Roche and Genentech have discontinued the GENERATION HD2 and POINT-HD programmes in Huntington’s disease after separate datasets showed no clinical benefit for tominersen and chronic dosing infeasibility for RG6496. Biomarker findings confirm huntingtin lowering, but future research must clarify its link to disease progression.
Written By: Anamika Koshti, Pharm D
Reviewed By: Pharmacally Editorial Team
Roche and Genentech informed Huntington’s disease (HD) patient community leaders on July 9, 2026, of a decision to discontinue both the GENERATION HD2 and POINT-HD clinical development programmes. The two decisions are independent, data-driven events that arose from separate datasets and coincidentally occurred at the same time. In a letter to the HD patient community, Roche acknowledged that the timing of these setbacks is deeply disappointing and reaffirmed its commitment to sharing all study data and learnings with the research community to support future HD drug development.
What is Huntington’s Disease?
Huntington’s disease (HD) is a rare, fatal, inherited neurodegenerative disease caused by an expansion of the CAG repeat in the HTT gene, leading to production of the mutant huntingtin protein. This abnormal protein progressively damages neurons, affecting movement, cognition, and behaviour. There is currently no approved disease-modifying treatment for HD. Both discontinued programmes enrolled people with early-stage HD, a period considered an important therapeutic window in which disease-modifying interventions may have the greatest opportunity to slow disease progression.
GENERATION HD2: Tominersen Phase II Results
The GENERATION HD2 study (NCT05686551) was a Phase II trial designed to validate a trend observed in the earlier GENERATION HD1 study in adults with early or very subtle symptoms of HD. The study enrolled 301 participants across 15 countries who received either tominersen 100 mg or placebo by intrathecal (spinal fluid) injection three times a year for a minimum of 16 months. Participants were aged 25 to 50 years, and clinical efficacy was evaluated using the composite Unified Huntington’s Disease Rating Scale (cUHDRS) and Total Functional Capacity (TFC) scores.
Top-line results from the primary analysis showed three key findings:
- Safety: Tominersen was well tolerated with no new safety signals.
- Biomarkers: Tominersen significantly reduced mutant huntingtin protein and Neurofilament Light Chain (NfL), a marker of neuronal damage that is elevated in people with HD, compared with placebo.
- Efficacy: Tominersen demonstrated no meaningful impact on clinical efficacy compared with placebo.
The biomarker findings confirmed that tominersen significantly lowered mutant huntingtin protein and NfL in study participants. However, these biological effects did not translate into measurable clinical benefit. Because the study met its safety and biomarker objectives but failed to meet its efficacy objective, Roche decided to discontinue further clinical development of tominersen for Huntington’s disease.
POINT-HD: RG6496 Phase I Discontinuation
POINT-HD (NCT07246941) was a Phase I, first-in-human study evaluating the safety and tolerability of RG6496 in adults aged 25 to 65 years with early HD. RG6496 was designed to selectively lower mutant huntingtin protein by targeting a specific single nucleotide polymorphism (SNP) in the expanded HTT gene. The study evaluated a single intrathecal dose and had enrolled three participants across sites in New Zealand, Argentina, and Australia, with plans to expand into Canada and Europe.
In parallel with the clinical study, Roche conducted longer-term non-clinical (animal) research to support future repeated-dose development. New findings from one of these studies indicated that RG6496 could not be administered chronically with repeated doses. Roche clarified that there were no safety concerns for participants who received the single dose. However, because the company could no longer offer participants the possibility of long-term treatment, it decided to discontinue the POINT-HD study. The enrolled participants will continue to be monitored according to the study protocol.
What Remains Active?
Roche’s Phase I/II study evaluating the investigational gene therapy RG6662 (formerly SPK-101; NCT06826612) remains ongoing as planned. The company also reaffirmed its commitment to exploring multiple therapeutic approaches for Huntington’s disease and continuing to follow promising scientific advances in the field.
What This Means for the HD Community
More than 1,500 HD families and members of the broader patient community contributed to the two programmes, with tominersen being studied since 2015 through Roche’s collaboration with Ionis Pharmaceuticals. Roche emphasized that these programmes demonstrated it is possible to lower the disease-causing mutant huntingtin protein in humans, an important scientific milestone that has shaped subsequent Huntington’s disease research.
At the same time, the GENERATION HD2 results showed that lowering mutant huntingtin protein and improving biomarkers alone were not sufficient to produce measurable clinical benefit in this study, underscoring the complexity of Huntington’s disease and the need for continued research. Roche has committed to completing the analyses and presenting the full data at future medical meetings so that the findings from both programmes can help guide the next generation of Huntington’s disease therapies.
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About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.