Many of you have asked LuMind RDS about the publishing of the results of the Hoffman-La Roche (Roche) trials that took place from 2011 to 2016 with their GABA-A targeting molecule basmisanil (RG1662) tested for improving cognition in people with Down syndrome. As you may know, Roche first conducted a small 35-person Phase 1 trial. That first trial was conducted to establish the drug’s safety and tolerability at different dose levels, as those aims are always at the forefront of any drug trial. The study demonstrated that basmisanil was safe and well tolerated over 5 weeks of treatment and showed some trends to improve cognition. Because 35 people is too few participants to make valid statistical claims about trial efficacy or the drug’s ability to make clinically significant changes in cognition, Roche then conducted two larger Phase 2 trials (in 173 participants ages 12-30 years – the CLEMATIS trial, and in 45 children ages 6-11 years – the pediatric trial). In 2016, a thorough data analysis of the CLEMATIS trial showed no positive effects with the drug candidate, and Roche decided to terminate the pediatric trial that was ongoing at the time.
Roche presented results from the CLEMATIS trial at the T21 Research Society meeting in Chicago in June 2017 showing the lack of efficacy on the primary endpoints in the trial (the RBANS for cognition, VABS-II for daily living/communication and socialization skills, and CGI-I as a measure of a clinician’s global impression of change). However, no information was presented last year on the secondary endpoints (i.e., cardiac changes, blood results, safety) and at the time Roche could not share in depth the full data supporting the reasons the drug candidate did not work in the CLEMATIS trial for individuals with Down syndrome.
LuMind RDS has been in contact with Roche, and they are in the process of preparing and submitting a paper around the more detailed results of the CLEMATIS study, including the secondary endpoints and more explanations for their decision to halt the pediatric trial. Roche is targeting to submit the paper for peer review by the end of 2018. When the paper is published, LuMind RDS will arrange a webinar with experts and/or representatives from Roche to share the information with you.
We wanted to, once again, thank all the individuals with Down syndrome who volunteered in the trials and their families for the support and time involved. Trial participation is an essential component of research, and the only way to bring promising new treatment options forward. In order to establish cutting edge standards of care for individuals with Down syndrome, more randomized and controlled treatment studies will need to be conducted, and we will all need to partner together – individuals with Down syndrome, families, clinicians, researchers, industry, Down syndrome foundations and the NIH – to make sure those studies are conducted with the utmost scientific rigor, eye to safety, and maximum engagement of those who care for and have family members with Down syndrome.
We are also very thankful to Roche for conducting one of the most rigorous trials to date in the Down syndrome population, and to all the researchers and clinicians involved at the 37 sites in the United States and internationally. Even though basmisanil did not show efficacy, it was an example of success in conducting a large study in individuals with Down syndrome. A lot was learned about how to optimally conduct larger trials in this population and the outcome assessments that may be improved in future trials.
We look forward to providing you with further updates later this year or early next year once the paper describing the CLEMATIS study has been published.