Update on Research & Clinical Trials

By Dr Rachel Harding  Edited by Dr Leora Fox

Scientists have found new leads for how to reduce the levels of the Huntington’s disease (HD) protein by targeting a protein called GPR52. A team of researchers working in Shanghai, China developed small drug-like molecules which lower huntingtin protein levels in HD tissue culture models and in HD mouse models. Treatment with their molecules was also shown to improve the HD mouse symptoms.

To read the full article, go to:  https://en.hdbuzz.net/298

The Huntington’s Disease Research Pipeline 


A research “pipeline” is the process of creating, testing, and ultimately approving a new drug for use in humans. HDSA funds researchers and doctors doing HD research at different stages along the pipeline, and collaborates with industry partners to bring information about clinical trials to the public. We alsofund human-centric research through the HD Human Biology Project and support young scientists through the Donald King Fellowships and Berman-Topper Career Development Fellowships. 


Wave Life Sciences Highlights Pipeline Progress and Expansion Leveraging New PN Backbone Chemistry Modifications
January 11, 2021 at 8:00 AM EST

Data from ongoing PRECISION-HD and OLE clinical trials for Huntington’s disease expected by end of 1Q 2021

PRECISION-HD clinical trials in HD: The PRECISION-HD1 and PRECISION-HD2 Phase 1b/2a and open label extension (OLE) trials evaluating WVE-120101 and WVE-120102 (respectively) in HD are ongoing. WVE-120101 and WVE-120102 are investigational stereopure oligonucleotides designed to selectively target the mHTT mRNA transcript, thereby leaving the wtHTT protein relatively intact.

  • The 32 mg cohorts added to both PRECISION-HD trials in 2020 are fully enrolled and dosing is underway in the multidose portions.
  • At the end of the first quarter, Wave expects to report data from both PRECISION-HD trials as well as available data from both ongoing OLE trials. These data are expected to enable a decision regarding potential Phase 3 development.
    º The analysis of PRECISION-HD2 will be comprised of biomarker and safety data from all cohorts, including all patients from the 32 mg cohort.
    º The analysis of PRECISION-HD1 will be comprised of biomarker and safety data from all completed cohorts, including all patients from the 16 mg cohort. Due to clinical site restrictions related to the COVID-19 pandemic, the last two patients in the PRECISION-HD1 32 mg cohort are currently scheduled to complete dosing in March 2021.
  • The OLE trials have been enrolling patients from PRECISION-HD2 since October 2019 and PRECISION-HD1 since February 2020. The vast majority of eligible patients from the PRECISION-HD trials have enrolled in the OLEs.
    º Patients in the PRECISION-HD OLEs have begun transitioning to the 32 mg doses.
    º PRECISION-HD2 patients have received up to 16 monthly doses of 8 or 16 mg of WVE-120102 in the OLE.
    º PRECISION-HD1 patients have received up to 9 monthly doses of 8 or 16 mg of WVE-120101 in the OLE.


Prilenia Initiates PROOF-HD Study of Pridopidine 

October 27, 2020.  Prilenia issued a press release last week stating that their drug pridopidine has entered a large Phase 3 clinical trial for HD. This study builds on a previous study of pridopidine in HD, which did not meet its key clinical goals. However, because the drug showed some promise for helping people with HD to maintain their daily functions, pridopidine will now be tested for longer in a larger group of people. According to the press release and a presentation at last week’s HSG conference, the study will enroll 480 participants aged 25 or older who have been diagnosed with HD. Participants will take pridopidine for up to 78 weeks (about a year and a half) and there will be an optional open-label extension, meaning that participants can opt to continue receiving the drug following the trial. Further details can be found here. There will be around 60 study centers in the U.S., Canada and Europe. As they begin recruiting, US and Canadian sites will be listed at www.hdtrialfinder.org and at https://clinicaltrials.gov/ct2/show/NCT04556656


Novartis Receives FDA Orphan Drug Designation To Study Potential HD Treatment

October 21, 2020.  This week the pharmaceutical company Novartis announced that they had received special status from the FDA, known as Orphan Drug Designation, to study an experimental drug called branaplam in HD patients. Novartis developed branaplam for the treatment of a genetic disease in children called spinal muscular atrophy (SMA). While testing it in animals and humans, they discovered that it can lower levels of the huntingtin protein, which is the culprit in HD. The exciting part: this drug is already known to be safe in patients with SMA, and is taken by mouth. The next step will be testing branaplam in larger numbers of people, to make sure it is safe for HD patients and see whether it could help with HD symptoms. Novartis plans to start a trial of branaplam in HD patients in 2021, and receiving Orphan Drug status will help them do so.