Roche\u2019s hypertension med\u00a0zilebesiran may have failed to hit the primary endpoint of the last in a trio of midstage studies, but the Big Pharma has insisted the data are promising enough to take the Alnylam-partnered drug into phase 3.<\/p>\n
The KARDIA-3 study was split into two cohorts of patients with uncontrolled hypertension. The first cohort consisted of 270 patients with estimated glomerular filtration rate (eGFR) of 45 mL\/min\/1.73m2 or higher, while the second cohort included patients with a lower eGFR, which is indicative of advanced kidney dysfunction.<\/p>\n
Overall, the study was unable to demonstrate a statistically significant change in systolic blood pressure (SBP) at Month 3\u2014missing the trial\u2019s primary endpoint and nullifying its secondary endpoints.<\/p>\n
Unveiling the data at the European Society of Cardiology Congress in Spain on Sunday, Roche\u2019s press release<\/a> blamed the miss on \u201ca multiplicity statistical testing approach,\u201d which required both the 300-mg and 600-mg dose cohorts to have a p-value of less than 0.05 or one dose cohort to have a p-value of less than 0.025.<\/p>\n Roche shared data from cohort A of the trial, where the 300-mg dose appeared to meet this mark with a 5 mmHg\u00a0placebo-adjusted change in SBP that equated to a p-value of 0.0431. However, the 600-mg dose undercut this result by only managing to demonstrate a 3.3 mmHg reduction.<\/p>\n Despite this top-line failure, Roche was keen to highlight that the study \u201cmet the aim of identifying the patient population that could potentially benefit the most from zilebesiran and also showed encouraging safety and clinically meaningful placebo-adjusted reductions in blood pressure.\u201d<\/p>\n The Swiss pharma drilled down into a subgroup of patients on diuretic therapy who began with an SBP of 140 mmHg or above. These patients saw their SBP drop by 9.2 mmHg\u00a0at three months, with these improvements sustained at a six-month follow-up.\u00a0<\/p>\n Roche said zilebesiran had once again demonstrated an encouraging safety profile when added to two or more background antihypertensives, usually an ACE inhibitor or an angiotensin receptor blocker. Serious adverse events were observed in 3.8% and 4.5% in zilebesiran and placebo-treated patients, respectively, with low rates of hyperkalemia, kidney dysfunction and hypotension.<\/p>\n Roche won\u2019t be sharing any data from the second cohort of KARDIA-3 until a future medical meeting but stressed that it is now planning to launch a 11,000-person phase 3 study of zilebesiran across more than 30 countries by the end of the year. It attributed the decision to the \u201ccomprehensive\u201d KARDIA program, which included the more successful KARDIA-1<\/a> and KARDIA-2<\/a> studies, which read out across 2023 and 2024.<\/p>\n \u201cZilebesiran has the potential to become a best-in-disease treatment for many patients with uncontrolled hypertension,\u201d Roche Chief Medical Officer Levi Garraway, M.D., Ph.D., said in the Aug. 30 release.<\/p>\n \u201cIts blood pressure-lowering effects and twice-yearly dosing could reduce the risk of serious health complications and death,\u201d Garraway added. \u201cDespite current treatment options, up to 80% of people with hypertension do not achieve adequate blood pressure control, putting them at higher risk of cardiovascular events.\u201d<\/p>\n Zilebesiran is a subcutaneously administered RNAi therapeutic that targets liver-expressed angiotensinogen. Roche secured the ex-U.S. and co-U.S. rights to the drug from Alnylam for $310 million upfront back in July 2023.<\/p>\n","protected":false},"excerpt":{"rendered":"Roche\u2019s hypertension med\u00a0zilebesiran may have failed to hit the primary endpoint of the last in a trio of…\n","protected":false},"author":2,"featured_media":81868,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":"","_share_on_mastodon":"0"},"categories":[124],"tags":[8386,1115,16594,42072,9275,1360,42250,134],"class_list":["post-81867","post","type-post","status-publish","format-standard","has-post-thumbnail","category-roche","tag-alnylam-pharmaceuticals","tag-biotech","tag-clinical-data","tag-failed-trials","tag-fierce-biotech-homepage","tag-genentech","tag-hypertension","tag-roche"],"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ch\/116733656955501340","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/posts\/81867","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/comments?post=81867"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/posts\/81867\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/media\/81868"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/media?parent=81867"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/categories?post=81867"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/tags?post=81867"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}