{"id":622473,"date":"2024-06-25T11:30:00","date_gmt":"2024-06-25T15:30:00","guid":{"rendered":"https:\/\/platohealth.ai\/wave-with-new-data-plots-path-forward-for-huntingtons-drug\/"},"modified":"2024-06-25T23:17:42","modified_gmt":"2024-06-26T03:17:42","slug":"wave-with-new-data-plots-path-forward-for-huntingtons-drug","status":"publish","type":"post","link":"https:\/\/platohealth.ai\/wave-with-new-data-plots-path-forward-for-huntingtons-drug\/","title":{"rendered":"Wave, with new data, plots path forward for Huntington\u2019s drug","gt_translate_keys":[{"key":"rendered","format":"text"}]},"content":{"rendered":"
WVE-003 is Wave\u2019s second attempt at designing an effective drug for Huntington\u2019s, after the company in 2021 shelved two prior candidates<\/a> that weren\u2019t potent enough in testing. All three candidates are meant to silence expression of mutated forms of the \u201cHTT\u201d gene, thereby reducing levels of mutant \u201chuntingtin\u201d protein that\u2019s toxic to neurons. (The resulting dysfunction and death of neurons is what causes the movement and thinking problems associated with Huntington\u2019s.)<\/p>\n However, WVE-003 was designed using different chemistry modifications, and targets another nucleotide in the RNA transcript produced by mutant HTT. The idea is the drug will selectively degrade mutant HTT protein while sparing the wild-type HTT protein thought to be helpful to normal brain function.<\/p>\n The trial data Wave disclosed Tuesday are evidence of this desired \u201callele selectivity,\u201d the company said. Participants in the study given three doses of WVE-003 had, on average, 46% lowering in mutant HTT protein levels in the cerebrospinal fluid, compared to placebo. Yet wild-type HTT protein levels were preserved and even increased, according to Wave.<\/p>\n \u201cWild-type huntingtin plays such a critical role in the central nervous system, and it\u2019s very exciting to finally have an opportunity to evaluate mHTT lowering in the context of allele-selectivity and to see positive signals emerging,\u201d Ralf Reilmann, founder of the George-Huntington Institute in Germany and lead investigator in Wave\u2019s study, said in the company\u2019s statement.<\/p>\n Researchers measured mutant HTT protein levels at week 24 of the study, two months after participants\u2019 last dose, and at week 28. Average protein lowering was maintained, at 44%, through the additional four weeks, Wave said.<\/p>\n The protein reductions surpassed analysts expectations of what would WVE-003 would need to show at this phase of testing.<\/p>\n Participants on treatment also \u201ctrended towards\u201d less caudate atrophy, which is imaged using MRI scans. In a presentation to Wave investors<\/a>, the company pitched caudate atrophy as a sort of intermediate measure between mutant HTT protein lowering and functional benefits. It also outlined a 12- to 18-month study of 150 Huntington\u2019s disease patients and measuring caudate atrophy as an \u201cefficient pathway\u201d to an accelerated approval.<\/p>\n But there were less positive signs in Wave\u2019s data, too. Cerebrospinal fluid levels of another protein, called neurofilament light chain or NfL, generally increased in participants given WVE-003, although Wave described the change as \u201cin line\u201d with the placebo group. NfL has become an increasingly important biomarker<\/a> in certain neurological diseases and is thought to be indicative of nerve cell damage.<\/p>\n The Huntington\u2019s field has also been disappointed before with drugs that reduced mutant HTT protein, but didn\u2019t lead to clear benefits<\/a> in motor function or cognition. Wave has emphasized \u201callele selectivity\u201d as a reason why it\u2019s drug could be different.<\/p>\n Shares in the company fell by as much as 11% in Tuesday morning trading.<\/p>\n PTC Therapeutics and Roche<\/a> are also working on Huntington\u2019s drugs designed to silence mutant HTT expression, while UniQure is developing a gene therapy<\/a>. Last week, the Food and Drug Administration lifted a partial clinical hold<\/a> it had imposed on a study of PTC\u2019s treatment.<\/p>\n Takeda Pharmaceuticals previously partnered with Wave on WVE-003, and holds an option<\/a> to co-develop and co-market the drug. Wave said it will submit its \u201copt-in package\u201d to Takeda.<\/p>\n Dive Brief: Wave Life Sciences on Tuesday said it will meet with regulators to discuss what kind of evidence would be needed to support an accelerated approval application for an experimental drug it\u2019s developing for Huntington\u2019s disease. The biotechnology company shared its plans alongside results from a placebo-controlled clinical trial testing the drug, dubbed WVE-003. […]<\/p>\n","protected":false,"gt_translate_keys":[{"key":"rendered","format":"html"}]},"author":2,"featured_media":622476,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[50],"tags":[],"acf":[],"gt_translate_keys":[{"key":"link","format":"url"}],"_links":{"self":[{"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/posts\/622473"}],"collection":[{"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/comments?post=622473"}],"version-history":[{"count":1,"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/posts\/622473\/revisions"}],"predecessor-version":[{"id":622475,"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/posts\/622473\/revisions\/622475"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/media\/622476"}],"wp:attachment":[{"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/media?parent=622473"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/categories?post=622473"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/platohealth.ai\/wp-json\/wp\/v2\/tags?post=622473"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}\n