Shares of Israel-based Intec Pharma Ltd. are down nearly 82% in premarket trading after the company announced its Phase III Parkinson’s disease therapy failed to demonstrate statistical superiority to treatment with Sinemet, a combination of carbidopa and levodopa.
Intec was evaluating the safety and efficacy of the Accordion Pill, also a combination of carbidopa and levodopa, in comparison to the immediate release Sinemet. The medication was being studied as a treatment for the symptoms of advanced Parkinson’s disease. Intec said the late-stage ACCORDANCE trial did not achieve statistical superiority to Sinemet on the primary endpoint of reduction in daily OFF time.
The primary efficacy endpoint of the study was the change from baseline to endpoint in the percent of daily OFF time during waking hours based on Hauser home diaries. The study was 90% powered to detect a one-hour difference in OFF time between Sinemet and AP-CD/LD. Under the protocol and conditions of the ACCORDANCE study, AP CD/LD did not demonstrate statistical superiority to Sinemet on daily OFF time, Intec announced.
Intec’s Accordion Pill Carbidopa/Levodopa (AP-CD/LD) is a gastric-retentive drug delivery system containing carbidopa and levodopa in both immediate and extended-release modes. The gastric retentive qualities were designed to provide a discharge of extended-release levodopa over 8–12 hours. The idea was to allow the active ingredients to be absorbed more steadily in the upper GI tract. Levodopa is the most widely used drug for the symptomatic therapy of Parkinson’s. However, chronic levodopa therapy can problematic due to the development of motor complications and may limit the usefulness of the drug, Intec said.
Intec Chief Executive Officer Jeffrey A. Meckler said that although the company is disappointed the trial did not hit its endpoints, the data suggests that AP CD/LD achieved an acceptable safety profile and did treat Parkinson’s disease symptoms.
Chief Medical Officer Michael Gendreau added that a review of the data showed certain subsets of patients saw a meaningful reduction in OFF time. He said the company will continue to analyze the full data set and “expect that such findings will help inform our strategy for AP-CD/LD moving forward.”
Parkinson’s disease is a neurodegenerative disorder. It affects dopaminergic neurons in a part of the brain. Disease symptoms typically develop slowly and could begin with slight tremors in the hands, slowness of movement or limb rigidity. Symptoms include tremor, slowed movement, rigid muscles, impaired posture and balance, loss of automatic movements and speech changes. People diagnosed with Parkinson’s often deal with times classified as “ON” and “OFF.” OFF periods are characterized by the re-emergence of Parkinson’s symptoms. In OFF times, which Inbrija addresses, patients experience periods of decreased mobility that are the result of low levels of dopamine between doses of oral carbidopa/levodopa. Over the course of the disease, patients OFF periods in patients can increase in frequency and severity. The “ON” time refers to when patients are responding to medication and symptoms are decreased.
OFF time is a common target for drug developers. In December, Acorda Therapeutics won approval for Inbrija, the first inhaled formula of levodopa (L-dopa) for the intermittent treatment of OFF episodes. Weeks after that approval, the U.S. Food and Drug Administration rejected Sunovion Pharmaceuticals’ experimental apomorphine sublingual film for the treatment of OFF episodes. In its rejection, the FDA requested additional information and analyses, but no new clinical studies. Earlier this month, San Diego-based Neurocrine Biosciences announced the FDA accepted its New Drug Application for opicapone as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing OFF episodes. The NDA for opicapone is supported by data from 38 clinical studies, including two Phase III studies, BIPARK-1 and BIPARK-2.