Neurocrine Biosciences Inc.’s tardive dyskinesia candidate, NBI-98854, nailed its endpoints in a Phase IIb (Kinect 2) study by causing a significant change from baseline in the abnormal involuntary movement scale (AIMS) after six weeks of treatment. Tardive dyskinesia is a syndrome characterized by involuntary, repetitive movements of the extremities. It has no approved treatment and is rarely reversible.
Neurocrine’s stock (NASDAQ:NBIX) gained $8.75, or 89.7 percent, on the unexpected news, to close Tuesday at $18.51.
The data came as a surprise after the disappointing results handed in for the previous Kinect study in September 2013. In that trial, a 50-mg dose of NBI-98854, a small-molecule VMAT2 inhibitor, did not meet its primary endpoint, while a 100-mg dose showed a statistically and clinically significant improvement. The Kinect 2 study, however, showed that at six weeks, AIMS scores were reduced by 2.6 points (49 percent) in the intention-to-treat group compared to a reduction of 0.2 points (18 percent) in the placebo group.
The San Diego-based biotech said it believes the strong results for Kinect 2 are a result of changes to the primary endpoint and the method of assessment, which will be used going forward in Phase III studies. In Kinect 2, evaluation of endpoints was done using video and blinded evaluators.
“Kinect-2’s use of a blinded ‘centralized’ rater rather than multiple ‘decentralized’ raters as in Kinect appears to have removed a considerable amount of background trial variability and allowed for measurement of statistically significant primary endpoint AIMS results at six weeks in both the intent-to-treat and per-protocol populations,” wrote Marko Kozul, an analyst with Leerink Partners. “Surprisingly, these Kinect-2 results were observed with dose escalation only to 75 mg rather than the 100 mg Neurocrine was planning to take forward in additional Phase II trials afterwards, based on disappointing Kinect results.”
The improvements on the same scale were confirmed by evaluations on the clinical global impression-tardive dyskinesia (CGI-TD) instrument. Using the CGI-TD, about 67 percent of subjects taking NBI-98854 were “much improved” or “very much improved” at week six compared to only 16 percent of placebo subjects.
The Phase II comeback will allow Neurocrine to submit an end-of-Phase II meeting request to the FDA and finalize a draft of its Phase III protocol. Those items will be filed with the FDA in the first half of 2014, the company estimated.
The intent-to-treat population of the trial at six weeks included 44 placebo subjects and 34 subjects randomized to NBI-98854, excluding 11 subjects whose plasma concentrations of NBI-98854 were below the lower limit of quantitation.
Neurocrine CEO Kevin Gorman explained in a conference call with investors that neuropsychiatric drug trials are plagued with professional trial subjects who enroll, receive payment and don’t take the study medication. The trial is therefore designed to exclude those subjects by screening for presence of the drug in the system at the time of evaluation.
The study was randomized, double-blind and placebo-controlled. Participants were affected with moderate to severe tardive dyskinesia and an underlying mood disorder, schizophrenia or schizoaffective disorder, or a gastrointestinal disorder with exposure to metoclopramide.
Safety analysis showed that NBI-98854 was generally safe and well tolerated. The rate of treatment-emergent adverse events was 33 percent for the placebo group and 43 percent for the NBI-98854 group. There were no drug-related serious adverse events.
Treatment emergent adverse events included fatigue and headache. An assessment for akathisia and parkinsonism showed minimal symptoms at baseline and no worsening during the six weeks of treatment.
The company plans to integrate data from the KINECT and KINECT 2 studies to inform its Phase III design, and that will form the basis of its package for the end-of-Phase II meeting with the FDA.
“It will take us the next several months to get the meeting on the FDA’s calendar. Look at that happening in first half of next year. Next summer would start on the Phase III study,” Gorman said.