FDA reviewers have raised a number of serious issues about the telmisartan application for an expanded indication. Telmisartan is now approved for the treatment of hypertension. The FDA Cardiovascular and Renal Drugs Advisory Committee will meet on Wednesday to evaluate the proposed indication for telmisartan to reduce risk of myocardial infarction (MI), stroke, cardiovascular (CV) deaths or hospitalization for congestive heart failure (CHF) in patients 55 years or older at high risk of developing major CV events. The expanded indication is based on data from one pivotal clinical trial, ONTARGET, and two supportive trials, TRANSCEND and PRoFESS.
The FDA reviewers raised questions about both the efficacy and safety of telmisartan. At the core of the efficacy review is the complex issue of whether telmisartan (an angiotensin-receptor blocker) is non-inferior to ramipril (an ACE inhibitor). The FDA reviewers write that the non-inferiority margin proposed by the sponsor (1.13) “seems too liberal.” It seems likely that a large part of the panel discussion on Wednesday afternoon will revolve around the definition and clinical significance of non-inferiority.
The FDA reviewers also found two safety signals in their review of the data, though it is unclear how serious these issues will be treated by the committee. Specifically, they found an increased rate of sepsis in the 3 clincial trials, though the difference did not achieve statistical significance. In addition, they found an increased risk of malignancies in the clinical trials. The reviewers acknowledge that the signals “are of uncertain clinical significance.”
Wednesday’s panel session may represent an interesting clash of the titans. Boehringer Ingelheim’s application will be presented by, among others, Salim Yusuf and James Young. The advisory panel will include Sanjay Kaul and Sidney Wolfe as a consumer representative. The panel chairman is Robert Harrington.
Click below to download the briefing materials:
July 29, 2009 Meeting of the Cardiovascular and Renal Drugs Advisory Committee
- July 29, 2009: Cardiovascular and Renal Drugs Advisory Committee Meeting Announcement
- Draft Agenda for the July 29, 2009 Meeting of the Cardiovascular and Renal Drugs Advisory Committee (PDF – 34KB)
- Meeting Roster for the July 29, 2009 Cardiovascular and Renal Drugs Advisory Committee (PDF – 23KB)
- Briefing Information for the July 29, 2009 Cardiovascular and Renal Drugs Advisory Committee
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