update on the Phase II GENERATION HD2 study
Roche announces study continuation and adjusts dosing strategy for tominersen in early-stage HD patients
What do we know?
Roche has announced the continuation of the GENERATION HD2 Phase II clinical trial evaluating tominersen in individuals with early signs of Huntington’s disease. Following an interim analysis by an independent committee, no safety concerns were identified. The higher 100mg dose showed a stronger potential for clinical benefit and will now be the sole dose tested moving forward. Participants on the 60mg dose will transition to the higher dose. The trial remains blinded, fully enrolled, and is expected to conclude in 2026.
Questions & Answers
Extracted from the community letter
What did the analysis results show?
The iDMC conducted the interim analysis and Roche does not have access to the data reviewed. We are modifying the GENERATION HD2 study based on the iDMC’s recommendations, which were to continue the study and to switch participants on the 60mg dose to the 100mg dose.
Does this mean that the 60mg dose did not work or was not safe?
The iDMC reviewed available trial data and did not raise any concerns regarding participant safety or signs of symptoms worsening with either tominersen dose. Roche is changing the GENERATION HD2 study design to only test the 100mg dose against placebo for the remainder of the study. This change is based on the iDMC’s recommendation that the 100mg dose was more likely than the 60mg dose to result in clinical benefit for people with HD.
Does this mean that the 100mg dose works?
The iDMC recommended that the 100mg dose should continue to be tested in the study, based on their review of interim data. The GENERATION HD2 study is ongoing and we cannot draw final conclusions at this time. The study is expected to complete in 2026.
Will study participants know which dose they were receiving? What does “blinding” mean?
From the start of the study, participants, study teams and Roche do not know treatment assignments. This is called “blinding” and it is done to avoid bias in how the study is run and results are obtained. When the study is “unblinded” after the end of the study, it will be possible for participants to learn which treatment group they were assigned – tominersen (including the dose) or placebo.
What happens now for study participants?
All participants will be contacted by their study sites and asked to consent to continue in the modified study. There will be no change to any participants’ overall study experience or schedules. After consent, the study pharmacy will switch the dosing of participants previously assigned the 60mg dose to the 100mg dose. There will be no change for participants previously assigned to the 100mg and placebo groups. Treatment assignments remain “blinded” to participants, sites and Roche.
What is an iDMC?
An independent Data Monitoring Committee (iDMC) is a group of experts external to a study, and independent of Roche, who periodically review accumulating data from an ongoing clinical trial. The committee monitors the safety of participants and the balance of benefits and risks of a clinical trial. Based on the reviews of data, an iDMC makes recommendations on how the trial is conducted.
What is an interim analysis and its purpose?
An interim analysis is a planned evaluation of data from an ongoing study before its completion. It allows researchers to make informed decisions about continuing, modifying, or stopping a study. Interim analyses are commonly part of study designs in order to avoid unnecessary study burden and patient exposure to an investigational drug.
Where can people go for more information?
Study participants and family members should contact their study site for questions. Community members can speak with their HD specialist or local patient organisations. Roche Medical Information can be reached at medinfo.roche.com.
What Happens Next?
● Investigators have been informed and they are starting to contact study participants about the study modification and next steps.
● The study is fully recruited and expected to complete in 2026.
● The iDMC will continue reviewing study data every 4-6 months to recommend whether to continue, modify or stop the study.