5 Deaths Force Acorda to Stop Enrollment in Phase III Parkinson's Trial

Acorda Therapeutics updated its Phase III clinical trial of tozadenant for Parkinson’s disease. Enrollment has been halted for new patients due to several deaths, and changes in the program have been made related to safety issues.

In both the Phase IIb study and the current Phase III study, about 890 patients received tozadenant and 234 have received placebo. There have been five fatalities out of seven patients with sepsis, all in the tozadenant group. Agranulocytosis is an absence of white blood cells, which are key immune cells. Four of the cases of sepsis were related to agranulocytosis, two had no white blood cell counts at the time of the event and one patient had a high white blood cell count.

In addition to pausing enrollment pending further review and discussions with the independent Data Safety Monitoring Board (DSMB) and the U.S. Food and Drug Administration (FDA), the company has increased the number of times it conducts blood cell counts on participants in the trial.

"We have taken these steps in the best interests of the safety of patients in the tozadenant studies, which is our top priority," said Ron Cohen, Acorda’s president and chief executive officer, in a statement. "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."

Tozadenant is an oral adenosine A2a receptor antagonist. It is in development as an adjunctive treatment to levodopa in Parkinson’s disease patients in an effort to reduce OFF time. OFF time refers to the motor fluctuations in Parkinson’s patients when the treatment, usually levodopa, is not working best and symptoms return.

On Oct. 31, the company reported its third-quarter financials. For the quarter, the company reported revenues of $141 million in revenue, with $399.9 million in revenue for the nine-month period. Acura reported cash, cash equivalents and short-term investments of $192.5 million, with total assets of $134.5 million for the quarter. Total operating expenses for the quarter were $143.2 million, with an operating loss of $2.2 million for the quarter. For the nine-month period, total operating expenses were $415.7 million with an operating loss of $36.7 million.

Cohen stated at the time, "We have had a constructive dialogue with the FDA since the issuance of its Refusal to File letter, and we plan to resubmit the Inbrija NDA in the fourth quarter. We believe our resubmission reflects a strong package that incorporate feedback we received from FDA. We are also on track to announce top-line data from our Phase III study of tozadenant in the first quarter of 2018."

Both tozadenant and Inbrija are being developed for Parkinson’s. Inbrija is for on-demand use to treat symptoms of OFF periods. Tozadenant is to increase overall ON time.

Company shares dropped about 34 percent after today’s news release. Shares are currently listed at $28.20, although it dropped to $17.85 in premarket trading.

In March, a judge struck down key patents related to Ampyra for multiple sclerosis (MS). Ampyra is responsible for most of the company’s revenue.