Acorda Therapeutics said today it will end development of its Phase III candidate Plumiaz™ (diazepam) Nasal Spray for treatment of epilepsy seizure clusters, citing disappointing data from ongoing clinical trials.
Acorda said Plumiaz failed to demonstrate its bioequivalence to Diastat® rectal gel, which was necessary to support a refiling of the nasal spray’s NDA previously planned for the first quarter of 2017.
Specifically, according to Acorda, the data showed unexpectedly lower nasal mucosa absorption of diazepam in persons with epilepsy compared to studies in healthy volunteers.
“We are very disappointed by this outcome, and for those in the epilepsy community who experience seizure clusters,” Acorda President and CEO Ron Cohen, M.D., said in a statement.
Acorda added that it will present data from the trials at an unspecified future medical conference.
Plumiaz won FDA’s orphan drug designation in 2012. The drug candidate had been under study for the treatment of seizure clusters in people with epilepsy. Acorda submitted an NDA to the FDA in 2013, only to receive a Complete Response Letter from the agency the following year.
Following talks with the FDA arising from the letter, Acorda last year initiated three clinical trials for Plumiaz:
- A long-term open-label study assessing safety and tolerability of Plumiaz over 52 weeks enrolling approximately 100 participants ages 12–65.
- A trial assessing the bioavailability, safety and tolerability of Plumiaz compared to diazepam rectal gel (Diastat®). The open-label, randomized, crossover trial was to enroll approximately 120 people with refractory epilepsy ages 12–65 who experience seizure clusters.
- A pharmacokinetic dose proportionality study in healthy adults.
The three trials will be discontinued, Acorda added.
“We will continue to focus on development of our other high-potential pipeline programs, including CVT-301 and tozadenant for Parkinson’s disease and dalfampridine for poststroke walking difficulty,” Dr. Cohen added.
CVT-301 is in Phase III development as a self-administered, inhaled levodopa (L-dopa) therapy for the episodic treatment of “off” periods in Parkinson’s disease. CVT-301 is being studied to provide delivery of a precise dose of L-dopa through the lungs to return people with Parkinson’s to an “on” state.
Tozadenant is an oral adenosine A2a receptor antagonist currently in Phase III development. Acorda said in January it will obtain worldwide rights to tozadenant through its planned acquisition of Biotie Therapies for $363 million, a deal expected to be completed in the third quarter of this year.
Dalfampridine—already marketed as Ampyra®, a treatment to improve walking in patients with multiple sclerosis—is now being developed as a once-daily (QD) formulation for chronic poststroke walking difficulty. In March, the company completed Phase I single-dose pharmacokinetic studies for three separate QD formulations of dalfampridine. Results for at least one of the formulations met the Company’s criteria. A multidose phase of pharmacokinetic testing is set to begin this quarter.
