FDA Panel Vetoes New Indication for Parkinson's Drug

An FDA advisory committee has voted 17 to 0 that Azilect (rasagiline), a drug that is already approved to treat symptoms of Parkinson's disease, does not work to slow progression of the neurodegenerative disorder.

Rasagiline was approved in 2006 to treat signs and symptoms of Parkinson's disease- such as tremors, difficulty walking, slowness of movement, and decreased facial expressions- either when used by itself or with levodopa.

The vote didn't come as a surprise given the roundly negative assessment that the drug was given for this indication by the FDA reviewers last week. The agency doesn't have to follow the advice of its advisory panels, but it often does.

Teva, the company that makes rasagiline, attempted to show that the drug also works to keep the disease at bay for a longer amount of time compared with not taking the drug, but the FDA's Peripheral and Central Nervous System Advisory Committee on Monday afternoon voted unanimously that the data don't support that claim.

There are currently no FDA-approved neurological drugs to delay disease progression.

The panel examined results from Teva's TEMPO trial - on which approval of rasagiline was based - which suggested that the drug might slow progression. To test whether rasagiline could actually alter the course of the disease, Teva performed the ADAGIO trial, in which more than 1,000 patients with untreated, early-stage Parkinson's disease were randomized to receive either 1 mg/day or 2 mg/day of rasagiline for 72 weeks, or placebo for 36 weeks and then rasagiline either 1 mg/day or 2 mg/day for 36 weeks, dubbed the "delayed start group."

Outcomes were measured using the Unified Parkinson's Disease Rating Scale (UPDRS), which measures mental ability, competence in completing activities of daily living, and motor skills. Patients in the all-rasagiline 1 mg/day group showed a 2.82-point worsening of symptoms on the UPDRS, compared with a 4.52-point worsening among patients in the "delayed start" group who received the 1-mg dose (P=0.02).

But that difference didn't hold true for the arms of the study that received 2 mg/day dosages. And in some instances - such as at the 72-week mark - the "delayed start" group was actually showing fewer signs of Parkinson's than the group that started medication earlier.

The panel spent much of the day discussing the delayed start study method, which assumes that if patients who start the drug later catch up to the patients in whom treatment was initiated earlier, then the benefit in the earlier-treatment group likely didn't alter the course of the disease.

It's a method that has been used in trial for Alzheimer's disease drugs, but the panel wasn't so sure it could be used to prove disease progression in Parkinson's trials.

The panel debated what would be the optimal design of a disease progression study, but didn't reach any conclusions.

Even patient groups couldn't endorse expanding the indication of rasagiline.

A joint statement issued by six Parkinson's organizations who called themselves "fiercely pro-investment, pro-progress, and pro-development," said there's not convincing evidence the rasagiline works to slow disease progression.

"While we are encouraged by the evidence presented to date, it appears to our community that the data surrounding Azilect as a therapy that slows clinical progression of Parkinson's are not yet definitive, and that additional information is required to completely determine the impact of Azilect on clinical disease progression," read the statement, which was from groups including The American Parkinson Disease Association and the Michael J. Fox Foundation for Parkinson's Research.

A neurologist on the panel said the negative vote on whether the rasagiline stops Parkinson's from progressing won't keep him from prescribing the drug to patients to treat symptoms of the disease.

"I will continued to prescribe this because it is safe, and it is effective," said Samuel Frank, MD, a neurologist and assistant professor of neurology at Boston University School of Medicine. "There is just not enough compelling evidence here for disease modification."