FDA Accepts Application for Inhaled Levodopa for OFF Periods in PD

February 21, 2018

The FDA had accepted a new drug application for the inhaled levodopa therapy for the treatment of OFF period symptoms in patients with Parkinson disease who are taking a carbidopa/levodopa regimen.

Burkhard Blank, MD

The FDA had accepted a new drug application for the inhaled levodopa therapy CVT-301 (Inbrija) as a treatment for OFF period symptoms in patients with Parkinson disease (PD) who are taking a carbidopa/levodopa regimen, according to a statement from Acorda Therapeutics, the company developing drug.

Under the Prescription Drug User Fee Act (PDUFA), the FDA will decide on the application by October 5, 2018. The application was based on findings from the phase III SPAN-PD trial, in which CVT-301 demonstrated significant improvements in motor function compared with placebo. The mean change in Unified Parkinson's Disease Rating Scale (UPDRS) part III at 30 minutes’ post treatment was -9.83 at week 12 with CVT-301 compared with -5.91 with placebo, representing a -3.92 difference between the 2 groups (P = .009).

“OFF periods greatly disrupt the lives of people living with Parkinson’s, and there is a significant need for new treatments in this community,” Burkhard Blank, MD, chief medical officer of Acorda, said in a statement. “We are excited about the potential to bring this highly innovative treatment option to people living with Parkinson’s, and look forward to working with the FDA throughout the review process.”

The SPAN-PD study assessed two doses of CVT-301, with the higher dose of 84 mg being selected for the FDA application. All patients had PD diagnosed between the ages of 30 and 85 years and were stage 1 to 3 in an ON state. Patients were on a levodopa dose of <1600 mg per day and could perform a spirometry maneuver in the ON and OFF states.

There were improvements in key secondary endpoints with CVT-301 at 84 mg over placebo. Overall, at 60 minutes, 21.6% more patients switched from OFF to ON with CVT-301 compared with placebo (P = .003). Overall, 57.7% of patients in the CVT-301 arm switch from OFF to ON compared with 36.1% with placebo.

With the 84-mg dose of CVT-301, 71.4% of patients had an improvement in PGIC scale versus 46.4% for placebo, which was a 25% improvement (P <.001). An improvement in UPDRS part III at 20 minutes and 10 minutes was also seen with CVT-301 compared with placebo. At 20 minutes, there was a -2.55 drop and at 10 minutes there was a -2.26 decline.

The most frequently reported adverse events for CVT-301 versus placebo, respectively, were cough (14.9% vs. 1.8%), upper respiratory tract infection (6.1% vs. 2.7%), nausea (5.3% vs. 2.7%), sputum discoloration (5.3% vs. 0%), and dyskinesia (3.5% vs. 0.0%). Most cases of cough were mild and were reported approximately once per patient. Only 2 of 114 patients receiving CVT-301 discontinued therapy due to cough.

Findings for the application were also submitted to the FDA from 2 long-term safety studies in Parkinson disease. These findings also supported the use of CVT-301 on an as-needed basis for OFF symptoms in patients with PD. Some of these early phase studies were supported by The Michael J. Fox Foundation.

“People with Parkinson’s and physicians need more options to manage this disease,” Todd Sherer, PhD, CEO of The Michael J. Fox Foundation, said in a statement. “Inhaled delivery of levodopa could help the many people living with Parkinson’s facing the complication of OFF periods as their disease progresses.”

If approved, the self-administered treatment could be used by the estimated 350,000 patients with PD in the United States who experienced OFF periods. OFF symptoms typically include impaired movement, muscle stiffness, and tremors.