Right on time, the FDA granted approval to Adamas Pharmaceuticals Inc.'s amantadine extended-release capsules (previously known as ADS-5102) for levodopa-induced dyskinesia (LID) associated with Parkinson's disease (PD). Marketing clearance was a prospect in which most onlookers, but not all, were confident ahead of the agency's edict. The drug will be marketed under the brand name Gocovri.

The company's stock (NASDAQ:ADMS) closed Thursday at $14.23 a share. News of the approval came after the market closed and there was little movement in after-hours trading.

Late last year, Emeryville, Calif.-based Adamas unveiled positive top-line phase III data from its EASE LID trial with M2 channel-targeting ADS-5102. The experiment met its primary endpoint, showing a statistically significant reduction (p = 0.0009) in LID at 12 weeks for patients who received ADS-5102 vs. placebo, as assessed by the Unified Dyskinesia Rating Scale. The outcome represents a 23 percent drop in LID for ADS-5102-treated patients compared to placebo, and LID knockdown held at 24 weeks (p = 0.0008), a key secondary analysis. In the study, four more key secondary analyses were made based on patient diary data. All achieved statistical significance. At week 12, ADS-5102 significantly increased "on" time without troublesome dyskinesia by 2.7 hours vs. placebo and reduced "off" time by 0.9 hours, effects that also remained steady at week 24. (See BioWorld Today, Dec. 24, 2016.)

The NDA for ADS-5102 was submitted in October 2016, bolstered by efficacy and safety data compiled from Adamas' full clinical program, including three placebo-controlled trials: EASED and two phase III studies, EASE LID and EASE LID 3. EASE LID 2, an open-label safety study, enrolled patients from EASED, EASE LID and EASE LID 3, as well as LID patients who have undergone deep brain stimulation. The EASE LID 2 trial is ongoing, and patients are being followed for up to two years, Adamas said.

Though amantadine is already approved to treat PD, no single drug is approved in the U.S. or Europe specifically to treat LID, Adamas' target indication. The company intends for ADS-5102 to address limitations of the current formulation by achieving top concentrations of the drug in the early morning through midday, when LID can be most problematic for patients, then dropping to lower levels in the evening, potentially reducing the negative impact of amantadine on sleep. The idea is to allow for higher doses of amantadine that can be tolerated with the immediate-release (IR) formulation, as well as making the once-nightly dosing easier to comply with.

Richard King, Adamas' chief operating officer, said during the conference call with investors on second-quarter earnings this month that the company had "done a fair amount of assessment of ADS-5102 with physicians and with payers. The profile for the product resonates extremely well, and they don't see this profile as really having much to do with the amantadine IR profile that's currently on the marketplace. They recognize that amantadine IR is not approved for this indication and that if ADS-5102 is approved for this indication, and with the clinical dataset that is available to support it, that there is no anticipation of requiring a step-through of amantadine IR to get to ADS-5102."

Mizuho Securities analyst Irina Koffler said in a research report last week that she was "cautiously optimistic" about the odds of approval for ADS-5102 after the earnings call, given "the company's sudden decision to utilize its own sales force and not a contract force (a pivot from the first quarter of the year). We find this strange, because management is extremely experienced and organized, in our view, and now plans to hire this team after the PDUFA and launch in January 2018, instead of having reps on standby with contingent offers," she wrote. Also, the firm "introduced new risk language in the 10-Q filing regarding the potential for new safety findings from the ongoing open-label safety trial to change FDA's interpretation of the data, and moved up statements that newly observed toxicities or worsening of [the drug's] known toxicities or FDA reconsideration of these toxicities could lead to increased regulatory scrutiny."

In Koffler's talk with officials at Adamas, they called it "normal to move up risk statements ahead of a PDUFA [date] and made a number of reassuring comments to indicate that it is 'feeling good' and also that its manufacturing is unlikely to pose a delay risk. Our overall take here is that the tone has grown more cautious and though the company may be in dialogue with the agency, [Adamas] could get some unfavorable safety language in the label or encounter a delay," she said. In the second-quarter report, the firm said its $145 million in cash could fund operations for at least another 12 months.

Worries were for naught, it turned out. Cowen and Co. analyst Ken Cacciatore had sounded much more sanguine as Wall Street waited, saying in a report earlier this month that, "given the robust clinical data package generated to date, we – and our consultants – continue to have a high level of confidence in approval."

Adamas said Gocovri will launch in the fourth quarter of this year and formally launched with the full deployment of Adamas' sales force in January 2018. A conference call with investors was slated for later Friday afternoon.