Dosing to stop in Phase III clinical study of tominersen following recommendation from an Independent Data Monitoring Committee (iDMC)

No new safety signals were identified for tominersen in the iDMC’s review

Basel, 22 March 2021 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced the decision to discontinue dosing in the Phase III GENERATION HD1 study of tominersen in manifest Huntington’s disease (HD). The decision was based on the results of a pre-planned review of the data from the Phase III study conducted by an unblinded Independent Data Monitoring Committee (iDMC). The iDMC made its recommendation based on the investigational therapy’s potential benefit/risk profile for study participants. No new or emerging safety signals were identified for tominersen in the review of the data from this study. Roche intends to continue following participants for safety and clinical outcomes, without the dosing of the investigational medicine or placebo. Once full data from the Phase III study are available and analysed, Roche will share learnings and future plans with the HD community.

Dosing will be paused in the open-label extension study (GEN-EXTEND) of tominersen while data are carefully analysed to inform next steps on this study.

“This is very unfortunate news to deliver on the tominersen Phase III study and we know it will be especially difficult for people with Huntington’s disease to hear. The HD community currently has no treatments to stop or slow the progression of this rare neurodegenerative disease that impacts families across generations.” said Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development. “GENERATION HD1 is the largest clinical trial in Huntington’s disease to date and we do know that the data generated will significantly advance our understanding of huntingtin-lowering as a potential treatment approach. We would like to thank all of the individuals and families participating in the study for their contribution, as well as the broader HD community for their commitment and collaboration.”

The Phase I PK/PD study (GEN-PEAK) of tominersen and the observational Roche HD Natural History Study will continue.

About tominersen and the clinical trials

Tominersen, previously IONIS-HTTRx or RG6042, is an investigational antisense therapy designed to reduce the production of all forms of the huntingtin protein (HTT), including its mutated variant, mHTT. In December 2017, Roche licensed the investigational molecule from Ionis Pharmaceuticals.

Tominersen is being investigated in HD in the following clinical studies:

GENERATION HD1: a randomised, multicenter, double-blind, placebo-controlled Phase III clinical study evaluating the efficacy and safety of treatment with tominersen in people with manifest HD over 25 months. Study participants were randomised to either 120 mg every-2-months or 120 mg every-4-months intrathecal injections of tominersen, or placebo. The study has recruited 791 participants from 18 countries around the world.

GEN-EXTEND: an open label extension study for participants coming from any Roche HD study. Participants receive 120mg tominersen every-2-months or every-4-months in the study.

GEN-PEAK: a Phase I study aiming to better understand the pharmacokinetics of tominersen and how tominersen affects mHTT levels and other markers in the spinal fluid and blood, which studies a range of doses from 30 mg to 120 mg of tominersen over two administrations.

About Huntington’s disease

Huntington’s disease is a rare genetic, progressive condition that causes the nerve cells in the brain to break down, causing problems with a person’s ability to think, move and function, leading to increasing disability and loss of independence. It has a devastating impact on people living with the disease, and the hereditary nature of HD means it profoundly affects entire families for generations. Survival ranges from approximately 10-20 years following motor onset of the disease. There is no known cure for HD and no approved therapies that treat the underlying cause.

About Roche in Neuroscience

Neuroscience is a major focus of research and development at Roche. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases.

Roche is investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Duchenne muscular dystrophy and autism spectrum disorder. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today.

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the twelfth consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2020 employed more than 100,000 people worldwide. In 2020, Roche invested CHF 12.2 billion in R&D and posted sales of CHF 58.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan