{"id":42323,"date":"2014-03-25T16:18:16","date_gmt":"2014-03-25T20:18:16","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=news&#038;p=42323"},"modified":"2014-03-25T16:18:16","modified_gmt":"2014-03-25T20:18:16","slug":"fda-reviewers-recommend-against-approval-for-novartis-heart-failure-drug","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2014\/03\/25\/fda-reviewers-recommend-against-approval-for-novartis-heart-failure-drug\/","title":{"rendered":"FDA Reviewers Recommend Against Approval for Novartis Heart Failure Drug"},"content":{"rendered":"<p>Ahead of an important advisory panel\u00a0<a href=\"http:\/\/www.fda.gov\/AdvisoryCommittees\/CommitteesMeetingMaterials\/Drugs\/CardiovascularandRenalDrugsAdvisoryCommittee\/ucm378911.htm\">FDA reviewers have recommended against approval of a novel drug for acute heart failure from\u00a0Novartis<\/a>.\u00a0The once highly promising drug, which\u00a0<a title=\"Novel Heart Failure Drug from Novartis Gains \u2018Breakthrough Therapy\u2019 Designation from FDA\" href=\"http:\/\/blogs.nejm.org\/cardioexchange\/news\/novel-heart-failure-drug-from-novartis-gains-breakthrough-therapy-designation-from-fda\/\">received a &#8220;breakthrough therapy\u201d\u00a0designation<\/a>\u00a0from the FDA last year, was turned down for approval in\u00a0Europe\u00a0earlier this year.<\/p>\n<p>On Thursday, the FDA&#8217;s\u00a0Cardiovascular and Renal Drugs Advisory Committee will discuss the biologics license application (BLA) for serelaxin injection\u00a0(proposed trade name Reasanz) from\u00a0Novartis. The indication is for the improvement of the symptoms of acute heart failure through reduction of the rate of worsening of heart failure. (The meeting was originally scheduled for February but was postponed due to weather.)\u00a0Serelaxin is\u00a0a recombinant form of the naturally occurring human hormone relaxin-2, which has been found to help women adjust to the cardiovascular changes that occur during pregnancy.<\/p>\n<p>The FDA reviewers raised critical questions and concerns about\u00a0<a title=\"RELAX-AHF Stirs Interest in Novel Drug for Acute Heart Failure\" href=\"http:\/\/blogs.nejm.org\/cardioexchange\/news\/relax-ahf-stirs-interest-in-novel-drug-for-acute-heart-failure\/\">the pivotal RELAX-AHF trial<\/a>, which was\u00a0published in the\u00a0<em><a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23141816\">Lancet<\/a><\/em>\u00a0in\u00a02012. The reviewers did not raise any safety concerns about the drug but stated that &#8220;there is insufficient evidence to support the proposed indication.&#8221;<\/p>\n<p>Generally, the reviewer notes, the FDA requires two independent trials to demonstrate a drug&#8217;s efficacy. But the RELAX-AHF trial, the single trial in support of the BLA, was further hampered because it successfully met only one of its two primary endpoints. Further, although the trial &#8220;was designed to assess dyspnea\u2026 the proposed claim is to improve the symptoms of acute heart failure.&#8221; Acute heart failure symptoms other than dyspnea &#8220;were not systematically measured in this study,&#8221; wrote the reviewer, who went on to then question the reliability and relevance of the dyspnea findings.<\/p>\n<p>The FDA reviewer also cast doubt on the reliability of\u00a0the surprising finding of a mortality reduction\u00a0at 180 days in the serelaxin group. Although the result adds confidence to the safety of the compound, the endpoint was not prespecified and needs to be confirmed in a follow up study before gaining acceptance. The reviewer also thought that additional doubt was raised because the mortality benefit had not been observed at an earlier time point, despite the fact that the drug is used acutely. (Novartis is currently conducting a large outcomes trial to confirm the mortality result.)<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Ahead of an important advisory panel\u00a0FDA reviewers have recommended against approval of a novel drug for acute heart failure from\u00a0Novartis.\u00a0The once highly promising drug, which\u00a0received a &#8220;breakthrough therapy\u201d\u00a0designation\u00a0from the FDA last year, was turned down for approval in\u00a0Europe\u00a0earlier this year. On Thursday, the FDA&#8217;s\u00a0Cardiovascular and Renal Drugs Advisory Committee will discuss the biologics license application [&hellip;]<\/p>\n","protected":false},"author":196,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[14],"tags":[549,322,196,1475],"class_list":["post-42323","post","type-post","status-publish","format-standard","hentry","category-heart-failure","tag-acute-heart-failure","tag-dyspnea","tag-fda","tag-serelaxin"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/42323","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/196"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=42323"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/42323\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=42323"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=42323"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=42323"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}