giving Tominersen a second chance

– Written by the Moving Forward team on February 7th, 2023

After a hard setback in March 2021, when Roche stopped the GENERATION HD1 trial because of potential safety issues, the company is now fully prepared to give its huntingtin-lowering drug, Tominersen, a second chance. In fact, at the end of 2021, a comprehensive data analysis led Roche to conclude that the drug seemed to have benefited younger people who began the trial in earlier stages of HD – see Moving Forward news piece here 

Therefore, Roche has decided to move forward and plan a second trial with Tominersen, the GENERATION HD2 trial, which will enroll participants who are younger and have milder HD symptoms than those enrolled in GENERATION HD1.

GENERATION HD2 is a phase 2 clinical trial that wants to evaluate the safety and efficacy trends of different dose levels of Tominersen compared with placebo in participants with prodromal and early manifest Huntington’s Disease.

The trial aims to recruit around 360 participants with subtle signs of Huntington’s disease (prodromal HD) or clinical symptoms of HD in an early stage (early manifest HD), aged 25 to 50 years, with a CAP score of 400 to 500. The CAP score is a research calculation based on age and the number of CAG repeats that is a predictor of disease state variables in HD. Potential participants will need to tolerate giving blood, having lumbar punctures and magnetic resonance imaging scans. They will also need to have someone who can be their ‘study companion’ throughout the trial. People involved in GENERATION HD1 will not be able to take part in GENERATION HD2 (except for those who participated in the placebo group), as this new study is testing Tominersen in previously untreated adults.

The trial is set to be conducted in 15 countries, namely Argentina, Australia, Austria, Canada, Denmark, France, Germany, Italy, New Zealand, Poland, Portugal, Spain, Switzerland, UK and USA. The participants will be split into 3 groups by chance and will receive spinal injections every 4 months for 16 months. These injections will have either a lower dose of Tominersen (60 mg), a higher dose of Tominersen (100 mg) or a placebo (injection with no drug). Participants and researchers are unaware of who belongs to which investigational group.

The researchers expect that lower and less frequent dosing at earlier HD stages will help uncover the positive impact of Tominersen in huntingtin lowering and overcome the safety issues identified in GENERATION HD1.

We believe that this new opportunity for Tominersen highlights the important role of people with prodromal and early manifest Huntington’s disease to advance research and we hope that the lower and less frequent dosing of Tominersen will make this trial less burdensome for them.

We also hope that the inclusion of countries such as Australia, Argentina and Portugal in this specific trial will expand the geography of HD research and bring new opportunities to those who really want to engage in HD studies and trials but haven’t had any opportunity until now.

Additionally, we believe that the incorporation of new assessment scales such as the HD-ISS into the GENERATION HD2 trial reinforces the importance of the scientific work constantly developed by HD researchers and strengthens the relevance of including people in preclinical disease stages in the research process. We think that this clinical trial may open the door for an active participation of asymptomatic people in HD research, which justifies and reinforces our commitment and efforts to provide support to this group within the Moving Forward project.

By investigating Tominersen for so many years, Roche has shown a long-term commitment to HD research, which is highly appreciated by the global HD community.

This commitment and the huge efforts of HD researchers and HD families who participate in clinical trials will continue the “CureHD” race, bringing us hope and belief in a better future without HD. 

More details about GENERATION HD2 can be found here: