briefing document<\/a> released ahead of the FDA committee meeting, FDA reviewers flagged \u201cdiscordant\u201d results from the two phase 3 trials.<\/p>\nThey noted that while study \u201c071\u201d was \u201crobustly positive,\u201d study \u201c072\u201d was \u201cclearly and convincingly\u201d negative and failed to demonstrate statistical significance on its primary or secondary endpoints.<\/p>\n
Given the conflicting phase 3 results, the company also provided the FDA with data from the \u201c061\u201d phase 2 study. However, the reviewers cited statistical and methodologic concerns with this study. The data from this study were \u201cretrospectively analyzed with post hoc multiplicity control methods to provide additional efficacy evidence, raising concerns about type I error inflation,\u201d the reviewers cautioned. The committee also had concerns about the 061 data analysis.<\/p>\n
Taken together, the data \u201cis not crossing that bar in my head,\u201d said committee member Jess Fiedorowicz, MD, PhD, head of the Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada.<\/p>\n
Walter Dunn, MD, PhD, director, Mood Disorders Section, West Los Angeles Veterans Affairs Medical Center, Los Angeles, agreed. Dunn said while he is a \u201cstrong advocate\u201d for increasing treatment options for PTSD, he was \u201cnot convinced\u201d of the efficacy of the combination given the conflicting data.<\/p>\n
Murray Raskind, MD, professor, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, felt it would be \u201chard to translate the confusing contradictory datasets to my clinical practice.\u201d<\/p>\n
Raskind also said he is not convinced the combination offers clinicians a new tool.<\/p>\n
Brexpiprazole is currently approved as adjunctive treatment of major depressive disorder in adults, treatment of schizophrenia in adults and adolescents aged 13 years or older, and treatment of agitation associated with Alzheimer\u2019s dementia.<\/p>\n
\u201cWe already have sertraline, and we already have brexpiprazole. The prescribing physician can make the decision to progress to the combination or start with it in the patient with PTSD,\u201d Raskind said. Other committee members agreed.<\/p>\n
Committee members in general felt that in the real world, co-initiation of both drugs may not be the preferred approach. It\u2019s more likely that clinicians would opt to start sertraline first, then add brexpiprazole if needed. \u201cThird-party payers may require that,\u201d Dunn predicted.<\/p>\n
During the public comment period, Michael Abrams, PhD, MPH, senior health researcher with Public Citizen, said the data supporting the use of this combination for treatment of PTSD is \u201cweak at best, based on two conflicting phase 3 trials and a questionable post hoc analysis of data from a phase 2 trial,\u201d and he urged the committee and the FDA to reject the combination.<\/p>\n
The lone \u201cyes\u201d vote for the brexpiprazole-sertraline combination in PTSD came from the patient advocate on the committee, Laura Block, PharmD, clinical pharmacist (retired), Cary, North Carolina.<\/p>\n
Block noted that while both of these individual component drugs are on the market, a third-party payer isn\u2019t likely to pay without an FDA-approved indication. \u201cThat means that there are those who are going to have difficulty accessing,\u201d Block commented.<\/p>\n
At the same time, Block said she would not want to offer patients \u201cdestructive false hope,\u201d and whether it is approved, she would like to see either a phase 3 or phase 4 study.<\/p>\n
Currently, the SSRI sertraline and paroxetine are the only FDA-approved medications for PTSD, and while these medications can be effective, many patients fail to achieve remission or discontinue treatment due to side effects or lack of response.<\/p>\n
The proposed upfront co-initiation of brexpiprazole with sertraline is a novel treatment paradigm. If approved by the FDA, it would be the first new treatment for PTSD in more than 20 years.<\/p>\n
The FDA is not required to follow the advice of its advisory committees, but it often does.<\/p>\n","protected":false},"excerpt":{"rendered":"An FDA advisory panel has resoundingly rejected the supplemental new drug application for the atypical antipsychotic brexpiprazole (Rexulti,…\n","protected":false},"author":3,"featured_media":84758,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[210,1060,50552,3977,67,132,68],"class_list":{"0":"post-84757","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-medication","8":"tag-health","9":"tag-medication","10":"tag-ptsd-post-traumatic-stress-disorder-post-traumatic-stress-syndrome-posttraumatic-stress-disorder-post-traumatic-stress-disorder-ptsd","11":"tag-u-s-food-and-drug-administration-united-states-food-and-drug-administration-fda-food-and-drug-administration-fda-food-and-drug-administration","12":"tag-united-states","13":"tag-unitedstates","14":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/114900161255913841","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/84757","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=84757"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/84757\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/84758"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=84757"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=84757"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=84757"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}