Trials Evaluate the First Allele-Specific Investigational Drugs for Huntington’s Disease, WVE-120101 and WVE-120102
Wave Life Sciences Ltd. (NASDAQ:WVE), a biotechnology company focused on delivering transformational therapies for patients with serious, genetically-defined diseases, today announced the initiation of the Company’s PRECISION-HD program, which includes PRECISION-HD1 and PRECISION-HD2, the Company’s two Phase 1b/2a clinical trials evaluating WVE-120101 and WVE-120102, respectively, for patients with Huntington’s disease (HD).
“Wave’s PRECISION-HD program is the first to target the underlying cause of Huntington’s disease with an allele-specific approach,” said Michael Panzara, MD, MPH, Neurology Franchise Lead of Wave Life Sciences. “Obtaining approvals to initiate these global studies as part of our first clinical program marks an important milestone for Wave. More importantly, these investigational compounds have the potential to address a critical unmet need for the HD patient community where no disease-modifying treatments are currently approved.”
PRECISION-HD1 and PRECISION-HD2 are Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled studies that will primarily evaluate the safety and tolerability of single and multiple doses of WVE-120101 and WVE-120102, respectively, administered intrathecally in HD patients. Additional exploratory objectives include assessing the impact that each compound has on the toxic mutant protein known to cause loss of brain cells in HD, as well as evaluating potential clinical effects and impact on brain atrophy as measured by magnetic resonance imaging (MRI). Both PRECISION-HD trials will follow the same protocol, and each will target a single nucleotide polymorphism, or “SNP,” that marks a separate and distinct location on the mutant huntingtin (HTT) gene transcript. Wave intends to enroll approximately 50 patients globally in each of the two studies through multiple sites, in Canada initially, with Europe and the United States to follow.
The PRECISION-HD trials for WVE-120101 and WVE-120102 will include adult patients with early manifest HD who carry a SNP at the rs362307(“SNP1”) or the rs362331 (“SNP2”) location, respectively. Potential HD patients for the PRECISION-HD program will be pre-screened for the presence of SNP1 or SNP2, and directed to the appropriate study upon qualifying for entry. Approximately two-thirds of all HD patients are expected to carry either SNP1, SNP2, or both, in association with the HD gene.
SNPs are a common type of genetic variation that normally occur in all humans, but may also act as biological markers to aid in locating genes associated with a particular disease. Previous HD research has identified multiple SNPs that are associated with the disease-causing expanded cytosine-adenine-guanine (CAG) repeat, which is an abnormality present in all HD patients that results in the production of mutant huntingtin protein, and causes HD. Therefore, Wave is utilizing common SNPs to precisely target the underlying cause of the disease.
“Reducing the disease-causing mutant huntingtin while preserving the healthy protein would be an important breakthrough for the HD community,” said Dr. Edward Wild, Principal Researcher at University College London Huntington’s Disease Centre, Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, London, and member of the PRECISION-HD Clinical Advisory Committee. “The pre-clinical data for Wave’s targeted compounds are encouraging and I am thrilled that we are beginning to explore the potential of these compounds in HD patients in this exciting programme.”
Source: WAVE Life Sciences