FDA staff recommends against heart failure indication for Bystolic (nebivolol)

FDA staff reviewers have strongly recommended that Bystolic (nebivolol) not receive a new indication for heart failure. The scathing review was published on the FDA’s website in advance of next Monday’s meeting of the Cardiovascular and Renal Advisory Drugs committee.

The recommendation of the clinical reviewer was about as clear and concise as you will ever find in an FDA document:

“Approval is not recommended for nebivolol for the treatment of heart failure.”

The following 100 pages provide a withering look at the faults of the SENIORS trial, including a marginal positive outcome and major midcourse changes in the trial with no clear or logical explanation:

Thus, in summary, the results from the SENIORS trial lack robustness. In addition, several critical changes were made late in the study that raise concerns as to the interpretability of the findings. Given these results and late changes to the trial, the totality of the evidence is not convincing to support a claim for treatment of heart failure.

The statistical reviewer concluded:

There is one study with a marginally significant p-value for the primary endpoint. For a single study, the FDA normally needs a small p-value, say less than 0.01, and internal consistency to support the claim. Changes to the study design while the trial was ongoing, neither component of the primary endpoint significant alone, and the lack of enrollment from the United States tend to weaken the results.

Meeting Materials for the January 11, 2010 Meeting of the Cardiovascular and Renal Drugs Advisory Committee: