Acorda Therapeutics, Inc., is discontinuing clinical development of its Parkinson’s disease treatment tozadenant after five people died of sepsis in late-phase trials.
Acorda announced that it is immediately ending dosing of all participants enrolled in its tozadenant studies. The company made this decision based on new information from the phase 3 program related to previously disclosed agranulocytosis (the absence of white blood cells, which fight infection) and associated serious adverse events. After analyzing this information, Acorda concluded that it could not be confident that weekly white blood cell count screening would sufficiently ensure patient safety. Acorda has informed regulatory authorities and trial investigators regarding the orderly closure of ongoing studies.
“Patient safety is our top priority,” said Ron Cohen, MD, Acorda’s President and CEO.
More than 90% of the participants in the placebo-controlled phase 3 efficacy and safety study, CL-05, have completed the study. Acorda expects data from these participants in the first quarter of 2018 and will present these at appropriate medical and scientific venues.
On November 15, Acorda disclosed the five sepsis deaths and said it would monitor patients more closely, suspend enrollment in long-term safety studies, and discuss next steps with the FDA and the trials’ independent Data Safety Monitoring Board (DSMB).
The phase 3 program included an ongoing pivotal efficacy and safety study (CL-05) and two long-term safety studies (CL-05 extension and CL-06). Including the previously conducted phase 2b study, about 890 patients have been exposed to tozadenant and 234 have been exposed to placebo. This corresponds to about 300 patient years of tozadenant exposure and 75 patient-years of placebo.
There have been seven cases of sepsis, all in the tozadenant groups, five of which were fatal. 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.
Tozadenant is an oral adenosine A2a receptor antagonist that was in development as an adjunctive treatment to levodopa in Parkinson’s disease patients to reduce off-time. A2a receptor antagonists would be the first new class of drug approved in the U.S. for improvement of motor symptoms in Parkinson’s disease in more than 20 years.
Following a successful phase 2b clinical trial, published in The Lancet in 2014, Acorda was conducting the CL-05 trial, in which tozadenant is taken for 24 weeks in addition to a person’s other Parkinson’s disease therapies. The trial was being conducted under a special protocol assessment from the FDA and was comparing two of the dose arms of tozadenant, 60 mg and 120 mg which were selected from the prior phase 2b clinical trial, versus placebo. The trial was assessing improvement of motor function and activities of daily living in people with Parkinson’s while taking tozadenant. The open-label, long-term safety study CL-06 had started enrollment in April 2017.