Acorda Therapeutics said today it has paused enrollment of new patients in its Phase III studies assessing its Parkinson’s disease candidate tozadenant after seven patients treated with the drug developed sepsis—five of whom died.
The enrollment pause will continue pending further talks with the studies’ independent Data Safety Monitoring Board (DSMB) and the FDA, Acorda said.
“Contingent on further input from the DSMB and FDA, we continue to expect to report efficacy and safety results of the double-blind Phase III study in the first quarter of 2018,” Acorda president and CEO Ron Cohen, M.D., said in a statement.
Four of the sepsis cases were associated with agranulocytosis, two had no white blood cell counts available at the time of the event, and one had a high white blood cell count, the company disclosed, without saying how many of the agranulocytosis-associated sepsis cases resulted in death.
In addition to pausing enrollment, Acorda said it has increased the frequency of blood cell count monitoring for patients in the studies. Including an earlier Phase IIb study, approximately 890 patients have been exposed to tozadenant and another 234, to placebo.
“We have taken these steps in the best interests of the safety of patients in the tozadenant studies, which is our top priority,” Dr. Cohen added.
Investors responded to the clinical setback with a selloff that sent Acorda shares sinking nearly 34% in after-hours trading this morning as of 9:15 a.m., to $18.70 from yesterday’s close of $27.70.
Tozadenant is an oral adenosine A2a receptor antagonist being developed as an adjunctive treatment to levodopa in Parkinson’s disease patients to reduce OFF time. A2a receptor antagonists have the potential to be the first new class of drug approved in the U.S. for improvement of motor symptoms in Parkinson’s disease in over 20 years, Acorda reasons.
Acorda acquired worldwide rights to tozadenant when it bought Biotie Therapies in a deal completed September 30, 2016, for $376 million.
Successful Phase IIb Study
Following a successful Phase IIb clinical trial, whose results were published in The Lancet in 2014, Acorda is conducting the Phase III CL05 trial (NCT02453386), in which tozadenant is taken for 24 weeks in addition to a person’s other Parkinson’s disease therapies.
The trial is being conducted under a Special Protocol Assessment, or SPA, from the FDA and is designed to compare two dose arms of tozadenant selected from the prior Phase IIb clinical trial (60 mg and 120 mg) to placebo. The trial is designed to assess improvement of motor function and activities of daily living in people with Parkinson’s while taking tozadenant. Data from the study is expected to be reported in the first quarter of 2018.
A separate open-label, long-term safety study dubbed CL06 (NCT03051607) commenced enrollment in April 2017. Primary outcome measures include Treatment Emergent Adverse Events (TEAEs), vital signs, electrocardiograms, and clinical laboratory tests.
The patient deaths associated with tozadenant mark Acorda’s third significant setback this year alone. In August, the FDA sent the company a Refuse to File letter in response to the company’s New Drug Application (NDA) for another Parkinson’s disease candidate, Inbrija™ (CVT-301). Acorda responded by promising to address the agency’s concerns, which focused on manufacturing and the drug master production record.
The following month, Acorda’s troubles prompted Scopia Capital Management, a New York hedge fund that owns 17% (approximately 7.7 million shares) of the company’s outstanding shares, to urge Acorda’s board to sell the company.
Worse, in April, Acorda disclosed plans to eliminate 20% of its workforce, in response to a federal judge invalidating four of the five patents protecting the company’s top-selling drug, the multiple sclerosis treatment Ampyra® (dalfampridine).