Five people have died of sepsis in late-phase trials of the Parkinson’s disease medication tozadenant (Acorda Therapeutics, Inc.), leading the company to 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).
Acorda said it increased the frequency of blood cell count monitoring for participants to weekly in its phase 3 program in response to cases of agranulocytosis, possibly drug-related, that have in some cases been associated with sepsis and death. Agranulocytosis is the absence of white blood cells, which fight infection. The phase 3 program includes an ongoing pivotal efficacy and safety study (CL05) and two long-term safety studies (CL05 extension and CL06).
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.
“Contingent on further input from the DSMB and FDA, we continue to expect to report efficacy and safety results of the double-blind phase 3 study in the first quarter of 2018,” said Ron Cohen, MD, Acorda's President and CEO.
Tozadenant is an oral adenosine A2a receptor antagonist in development 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 more than 20 years.
Following a successful phase 2b clinical trial, published in The Lancet in 2014, Acorda is conducting the CL05 trial, 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 from the FDA and is 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 is assessing improvement of motor function and activities of daily living in people with Parkinson’s while taking tozadenant. Data from this trial are expected in the first quarter of 2018. A separate open-label, long-term safety study (CL06) commenced enrollment in April 2017.
Acorda has a pipeline of novel neurological therapies addressing a range of disorders, including Parkinson’s disease and multiple sclerosis. Acorda markets two FDA-approved therapies, including Ampyra (dalfampridine) extended release tablets, 10 mg.
Source: Acorda; November 15, 2017.