Acorda Therapeutics said today it has terminated development of its Phase III Parkinson’s disease candidate tozadenant, just five days after pausing enrollment in two pivotal trials following the deaths of five patients.
The five were among seven patients who developed sepsis in the Phase III studies. 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 on November 15, without saying how many of the agranulocytosis-associated sepsis cases resulted in death.
Acorda said today that its decision to halt tozadenant development stemmed from new information gathered from the Phase III program “related to previously disclosed agranulocytosis and associated serious adverse events.”
Without detailing the new information, Acorda “concluded that it could not be confident that weekly white blood cell count screening would sufficiently ensure patient safety.”
Acorda said it will immediately discontinue dosing of all participants currently enrolled in its tozadenant studies and has informed regulators and trial investigators of plans for an “orderly” end to ongoing studies.
“While we are deeply disappointed by this outcome, we remain committed to the Parkinson’s community, which is in great need of new therapeutic options,” Ron Cohen, M.D., Acorda’s president and CEO, said in a statement.
The Phase III trials in question included the CL-05 trial (NCT02453386), in which tozadenant was taken for 24 weeks in addition to a person’s other Parkinson’s disease therapies, and a separate open-label, long-term safety study dubbed CL-06 (NCT03051607), which began patient enrollment in April 2017.
CL-05 was designed to compare two dose arms of tozadenant selected from the prior Phase IIb clinical trial (60 mg and 120 mg) to placebo, with the goals of assessing improvement of motor function and activities of daily living in people with Parkinson’s.
Acorda said today that more than 90% of the participants in CL-05 have completed the study, which had an estimated enrollment of 450 patients. Data from those patients is expected to be available in the first quarter of 2018 for presentation at unspecified “appropriate medical/scientific venues.”
CL-06 called for patients to begin dosing with tozadenant at a dose of 120 mg twice daily or “BID.” At week 2 or thereafter, the investigator had the option of adjusting the patient's investigational medicinal product (IMP) dose as clinically indicated, with doses of 60 mg BID and 120 mg BID permitted. Primary outcome measures for CL-06 included Treatment Emergent Adverse Events (TEAEs), vital signs, electrocardiograms, and clinical laboratory tests.
Tozadenant is an oral adenosine A2a receptor antagonist developed as an adjunctive treatment to levodopa in Parkinson’s disease patients to reduce OFF time. A2a receptor antagonists showed potential for being 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 reasoned.
Acorda acquired worldwide rights to tozadenant when it bought Biotie Therapies in a deal completed September 30, 2016, for $376 million.