Inhaled Levodopa Shows Promise in Phase 2b
Phase 2b data for Acorda Therapeutics’ Inhaled levodopa (CVT-301) therapy presented at the 19th International Congress of Parkinson’s Disease and Movement Disorders show that it provides rapid motor improvement in Parkinson’s disease (PD). CVT-301 is being developed to treat OFF episodes; Following inhalation, concentrations rise rapidly within approximately ten minutes to therapeutic levels.
Eighty-six patients were randomized to receive either CVT-301 or placebo. Onset of action was based on UPDRS III score improvements. With an average daily use of approximately two times per day, CVT-301was associated with a 1.6-hour reduction in daily OFF time, or a 30-35 percent reduction from baseline during the period of use, according to a report presented at the 19th International Congress of Parkinson’s Disease and Movement Disorders. In addition, no increase in ON time with dyskinesia was evident. Treatment was well-tolerated with a low incidence of side effects.
Study investigator, Robert A. Hauser, MD, Director, Parkinson’s Disease and Movement Disorder, Neurology and Professor, Neurology, University of South Florida spoke with Practical Neurology® about the significance of the findings. “The Phase-2B was a placebo controlled study, so of course, that stands out…What also stood out was the result with regard to efficacy as well as safety,” Dr. Hauser says.
New avenues for delivery of levodopa are welcome by clinicians, Dr. Hauser notes. “Despite the medications that we have available, off episodes are prevalent and we don’t really have the tools yet to eradicate them, or even adequately treat them. We still need good, easy to administer, treatments for off episodes,” he says. “Ideally, such treatments would work quickly and fill the gap between other treatments, particularly oral Levodopa. You’d like to see therapies that work quickly and last, typically, somewhere 60 to 90 minutes until the next oral levodopa dose kicks in.”
The study included both in-clinic and at-home use and evaluations. In-clinic, patients’ Parkinson motor scores were evaluated from 0 to 60 minutes. “For both the lower dose, which was 35mg and the higher dose, 50mg, there was a significantly better improvement in motor scores from 10 minutes all the way out through 60 minutes. So, an improvement in 10 minutes suggests that there is a rapid onset of action and suggests that this could potentially be beneficial for many patients who are experiencing off episodes,” Dr. Hauser observes.
Findings from the Phase 2b study warrant further investigation, Dr. Hauser suggests. In Phase 3 trials, he says. “We would like to see a replication of the difference between placebo and active medication in the in-office visit. We’ll be looking to confirm early onset of action and maintenance of benefit through the 60-minute time frame. In the Phase -2B study, patients were only allowed to take study medication at home up to 3 times per day. In Phase-3, they’ll be allowed to take it up to 5 times per day. We’ll be looking to see how much benefit CVT-301 provides compared to placebo with regard to home use.”