FDA Guidance Sought for Planned Trial of Ketamine to Treat Dyskinesia

Pharmather has filed a request to meet with the U.S. Food and Drug Administration (FDA) to determine next best steps in the clinical development of ketamine to treat the levodopa-induced dyskinesia associated with Parkinson’s disease.

The filing is in preparation for a proposed Phase 2 clinical study of ketamine, an FDA-approved prescription anesthetic and pain killer, in Parkinson’s patients. Those enrolled in the trial will be treated with low, or sub-anesthetic, doses of ketamine.

“We are pleased to have taken this important step in advancing our ketamine program for Parkinson’s disease via the FDA regulatory pathway, which is part of our overall strategy of progressing our novel ketamine prescription-based therapies to treat neurological disorders for FDA approval,” said Fabio Chianelli, Pharmather CEO, in a press release.

“We look forward to finalizing our Phase 2 clinical study for ketamine in Parkinson’s disease and leveraging the pre-IND [investigational new drug] meeting to unlock additional value in our exclusive FDA-based ketamine programs in depression and pain.”

Pharmather aims to advance its portfolio of ketamine therapies for Parkinson’s disease, depression and pain. The hope is that the pre-IND meeting provides information that will pave the way for the company to conduct a Phase 2 trial in the U.S.

As sponsors such as Pharmather begin to invest significant amounts of time and money developing a product, they seek guidance from the regulatory agency that might eventually decide whether that product merits approved. Pre-IND meetings help to inform preclinical and clinical planning, increasing the probability of a successful development program.

Pharmather filed a request with the FDA in October, requesting orphan drug designation for ketamine in treating dyskinesia in Parkinson’s. The condition, which is marked by involuntary jerky movements, affects roughly half of those using levodopa within the four or five years of its use, and about 80% after 10 to 12 years. Levodopa is one of the main therapies used to treat Parkinson’s motor symptoms, such as stiffness and slowness of movement.

The FDA grants orphan drug status to investigational therapies with the potential to help people with a rare disease. The designation also bestows certain benefits, such as additional agency support, if the therapy is approved.

Ketamine is frequently used to start and maintain anesthesia during brief surgical procedures. Its use is restricted due to its psychological effects, and its potential for abuse as a recreational drug.

University of Arizona scientists recently published a case study series, showing early evidence that low doses of ketamine were safe and tolerable, and might provide long-term relief of dyskinesia, and ease depression and pain in Parkinson’s patients. “We hypothesize that low-dose ketamine may act as a ‘chemical deep brain stimulation’,” the researchers wrote, adding that a “low-dose ketamine infusion … should be further investigated in a properly controlled prospective clinical trial.”

Findings in mouse model of levodopa-induced dyskinesia also supported ketamine’s potential in treating dyskinesia. Pharmather recently entered into an exclusive licensing agreement with the University of Arizona to develop ketamine for Parkinson’s.

Parkinson’s is believed to affect more than 1 million people in the U.S., and more than 7 million people worldwide.