Acorda Therapeutics has announced phase III clinical data of CVT-301, showing a statistically significant improvement in motor function in people with Parkinson’s disease experiencing OFF periods. CVT-301 is an investigational, inhalable formulation of levodopa (L-dopa). It is being studied as a treatment for OFF periods in people with Parkinson’s disease taking an oral carbidopa/levodopa regimen. OFF periods refer to the re-emergence of Parkinson’s symptoms.

“We are greatly encouraged by the efficacy and safety results of this trial, which validate the positive phase IIb results,” said Burkhard Blank, M.D., chief medical officer of Acorda. “We would like to express our gratitude to the study volunteers and clinical investigators who participated in this trial to advance our understanding of this potentially important therapy for people with Parkinson’s.”

The SPAN-PD trial had three arms: CVT-301 84mg and 60mg doses (equivalent to 50mg and 35mg fine particle doses, respectively), and placebo. The primary endpoint of the study was the change at Week 12 in Unified Parkinson’s Disease Rating Scale-Part 3 (UPDRS III) score relative to placebo at 30 minutes post-treatment for the 84mg dose. UPDRS III change for the 84mg dose was -9.83 compared to -5.91 for placebo (p=0.009). UPDRS III is a validated scale, which measures Parkinson’s motor impairment.

The safety profile of CVT-301 in this study was consistent with that observed in the phase IIb trial. Spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) tests showed no notable pulmonary safety signals. The company is currently conducting two studies to assess the long-term safety profile of CVT-301. Up to 12-month data from these studies are expected by the end of the first quarter of 2017.

The company plans to file a New Drug Application (NDA) in the U.S. by the end of the second quarter of 2017, pending results of the long-term safety studies. The company also plans to file a Marketing Authorization Application (MAA) in Europe by the end of 2017, pending additional data analyses.

Peter LeWitt, M.D., M.Med.Sc., director of the PD and Movement Disorders Program at Henry Ford Hospital and lead investigator of the study, said, “The re-emergence of Parkinson’s disease symptoms has a major negative impact on the lives of people with this disease, as well as on their families and care partners. Managing symptoms of OFF periods continues to be a significant unmet need for people taking oral carbidopa/levodopa regimens. Delivering levodopa by the pulmonary route offers an important treatment option for people with Parkinson’s disease.”

Participants reporting serious adverse events (SAEs) were as follows: 3 (2.7%) in the placebo arm, 6 (5.3%) in the 60mg arm, and 2 (1.8%) in the 84mg arm. There was one death in the study, a suicide in the 60mg group, judged by the investigator to be not related to study drug.

When cough was reported, it was typically mild and reported once per participant during the course of treatment. Three of 227 participants receiving CVT-301 discontinued the study due to cough.

The phase III, randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of CVT-301 compared with placebo in people with Parkinson’s who experience motor fluctuations (OFF periods). All participants were on a stable regimen of oral carbidopa/levodopa, and were also maintained on their other existing Parkinson’s therapies. A total of 339 study participants were randomized and received at least one dose of CVT-301 or placebo. Participants self-administered treatment up to five times daily for 12 weeks.

The primary endpoint of the study was the change at Week 12 in Unified Parkinson’s Disease Rating Scale-Part 3 (UPDRS III) score relative to placebo at 30 minutes post-treatment for the 84mg dose. Key secondary endpoints, measured at Week 12, included: proportion of participants achieving an ON state within 60 minutes of treatment and maintained at 60 minutes; change in UPDRS III score at 10 and 20 minutes following treatment; Patient Global Impression of Change (PGI-C) improvement; and total daily OFF time as recorded in participant diary.