Multiple pieces of news about ongoing clinical trials were shared this week by companies developing therapies for HD. We discuss those announcements in more depth in the blog today, and point you to their sources. HDSA will be hosted a webinar on Thursday, August 11, 2022, from 12PM-1PM (ET), to offer people a chance to learn more, share, and listen. Members of the HDSA team reviewed what we know and don’t know, provided helpful resources, and answered questions as best were able. CLICK HERE TO WATCH THE RECORDING.
If you or someone you know needs support around any of the information shared this week, reach out to us through the HDSA Helpline at (800) 345-4372 or click here to access any of our community and social support services and programs.
Dosing of Branaplam halted in Novartis’ VIBRANT-HD study
Novartis has shared with participants, investigators, and community organizations that dosing of branaplam has been suspended in the VIBRANT-HD trial. Branaplam is an oral drug originally developed for kids with spinal muscular atrophy. It was found to also lower levels of harmful huntingtin protein, which is found in the cells of the brain and body in people with HD. It is being studied in a clinical trial called VIBRANT-HD, which was designed to test the safety of branaplam and its ability to lower levels of huntingtin protein in adults with HD. The trial sought to recruit 75 participants across 11 countries for weekly doses of branaplam.
The first group (cohort) of around 20 participants was taking a low dose of branaplam, with about 5 taking a placebo control, and if all had looked safe and tolerable, a higher dose would have been tested in more people. Unfortunately, after reviewing the initial findings, an independent Data Monitoring Committee found evidence that branaplam could have concerning side effects. Some of those in the low dose cohort had started to experience peripheral neuropathy and had other signs of potential harm to the nervous system. This can come, for example, in the form of altered reflexes, the feeling of pins and needles or pain in hands and feet. For this reason, Novartis decided to pause dosing, but the study is ongoing. Participants are encouraged to continue their study visits, an essential step towards learning whether it makes sense for Novartis to move forward with testing branaplam in people with HD. We don’t have a lot of answers right now as to why these unfortunate side effects are occurring, but HDBuzz broke down the news in more depth in their latest article. Click here to read the complete story.
uniQure announces serious adverse events in some participants receiving high doses of AMT-130
Also on Monday, as part of an announcement of its second quarter 2022 financial results, uniQure shared the news that high-dose procedures in their HD study will be put on hold. The main goal of this small study is to determine a safe dose of the huntingtin-lowering gene therapy AMT-130, which is delivered by brain surgery. It has been ongoing for a couple of years in the US and Europe. In June uniQure announced good news about safety and huntingtin lowering in the first 10 people who received a low dose of AMT-130. Information included in the latest investors’ report, from Monday August 8th, unfortunately showed that three (out of 14) participants who received a high dose of AMT-130 experienced unexpected severe side effects in the couple of weeks following the surgery. These included things like headaches, dizziness, vomiting, and some other neurological signs.
It’s not clear exactly why this happened with the higher dose; perhaps a strong immune reaction – but high dose surgeries have been put on hold until further safety review. However, there’s strong potential to resume with new monitoring in place. We will likely hear more information soon about how they plan to proceed with the high dose group, and then further data from the full low dose group in 2023. As was announced in June, a one-year safety review indicated that the drug has been well-tolerated at the low dose with no significant safety concerns and lower levels of huntingtin observed after the first year of follow-up. Read the full press release here.
SAGE Therapeutics announces initiation of Phase 2 SURVEYOR study
This week also brought good news for the HD community; Sage Therapeutics announced on Wednesday that they’ve opened enrollment in the SURVEYOR study, a Phase 2, real-world functioning study of the experimental drug, SAGE-718. The SURVEYOR study is the second part of Sage’s PERSPECTIVE program, a series of studies to evaluate the safety and efficacy of SAGE-718. This drug is taken by mouth and is aimed at addressing cognitive decline in HD and related neurodegenerative diseases. The first study to open in this series was Sage’s Phase 2 DIMENSION study to test the safety and efficacy of the compound, which is also actively recruiting in North America. The SURVEYOR study will build upon the DIMENSION study by evaluating SAGE-718’s effects on real world tasks; the study protocol will include things like an optional driving simulation and virtual reality experiences to simulate tasks of daily living. These tests will be used to observe differences in cognitive performance between people with early HD symptoms and people without HD, and to confirm the safety and efficacy of the drug. To learn more about the study and whether you may be eligible to participate, visit HDTrialfinder. Sage expects to launch the last study in the PERSPECTIVE series, an open-label safety study, by the end of 2022. To read the full community letter, click here.