An FDA advisory panel of outside experts weighed the data on the risks and potential benefits of using Acadia's ($ACAD) Nuplazid (pimavanserin) as a new antipsychotic for Parkinson's patients, and most concluded that it should be OK'd for commercial use at this point.
The panel came down heavily in favor of the established efficacy of the drug, with 12 voting "yes" on whether the company had provided convincing positive data, compared to two votes against. Several members of the advisory group said they were influenced by the absence of approved therapies for the indication. And even with a clear set of issues related to the safety of the drug, as presented by regulators, several of the experts were won over by the idea of approving the drug now and demanding more work on the therapy later.
The panel voted 12 to 2 that the drug's benefits outweighed the risks of taking it.
After staying in limbo through the day, Acadia's shares shot up 23% on Tuesday evening.
"The positive AdComm renders FDA approval, on or before ACAD's PDUFA of May 1st, very likely, in our view," notes Leerink's Paul Matteis. "Upon approval, we believe investors will be focused on labeling language--while FDA members stated they had not decided on a black box (BB), we believe panelist commentary and FDA precedent suggest a BB is very likely, which we see as largely in with consensus."
The FDA's analysis put a bright spotlight on just what the drug's potential benefits would cost. Their task was complicated by the fact that many of the standard therapies now in use on an off-label basis are all tied to an increased risk of death.
"This is a medically frail population," noted the FDA's Paul Andreason, an agency medical officer and psychiatrist who readily acknowledged the positive efficacy data offered on the drug in the pivotal study, which illustrated the drug's ability to reduce psychotic events for patients. The problem with pimavanserin, though, is the data also underscored a significantly increased risk of deaths and serious adverse events. The challenge for the panel, he said, was determining if the risk/benefit equation came out in favor of the drug, or against it.
Andreason then ran through a series of conclusions, drawing a bottom line on the chances of a major reduction in disease symptoms and the rising risk of patient danger as the dose increased. For the regulator, the key was determining how many patients had to be treated in order to do some real good, like keeping "somebody out of the nursing home." That kind of benefit could be limited to a ratio of one out of 5 treated patients.
"In summary," he wrapped up with the panel, "you need to treat 91 people for 7 full (therapeutic) responses" while tracking 5 serious adverse events, "one of which will result in death."
A number of experts criticized the single study with limited targets that the company used for the application. The agency also highlighted problems with the size, noting that it included only a relatively small number of patients, where the data could have been influenced by small shifts in outcomes between the drug and placebo arms. And that discussion may well lead to changes in trial design for future applicants.
The final decision on a near-term approval now shifts to the FDA. And the agency's final decision will have a major impact on San Diego-based Acadia. Analysts have pegged 2020 revenue from Nuplazid at $1.4 billion, making this one of the top drug prospects up for review this year. It remains to be seen, though, just how those forecasts could be influenced by today's debate.
The FDA has designated the therapy as a "breakthrough" drug warranting a quick response from regulators.