According to Acorda, seven cases of sepsis have been reported out of a total of 890 patients who have taken tozadenant, including those enrolled in a previous Phase IIb trial.
Of those seven patients, five died and four developed a condition known as arangulocytosis. No sepsis or arangulocytosis occurred among the 234 placebo patients taking part in the trials. Acorda noted that some of these incidents could be related to tozadenant treatment, but it is not yet certain whether tozadenant was the original cause of these patients’ deaths.
The company opted to immediately pause the dosing of all participants who are currently enrolled and terminate the tozadenant trials, but it still plans to wrap up the trial data. Results from these trials are expected in Q1 2018.
In January 2016, Acorda acquired Biotie Therapeutics for $363M, which brought with it the global rights to tozadenant. Tozadenant is an oral adenosine A2a receptor antagonist developed as an adjunctive therapy to reduce OFF time in advanced-stage PD patients who are taking a carbidopa/levodopa regimen. The A2a receptor is localized within the striatum of the brain and is thought to antagonize the D2 receptor, prompting its investigation in PD.
There is a substantial need for novel therapeutics targets in the PD market due to a lack of disease modifying drugs and treatments for non-motor symptoms. However, clinical trials have not yet shown promise for this indication, with the failure of Merck’s preladenant, an initial rejection from the FDA for Kyowa Hakko Kirin’s Nouriast (istradefylline), and now the termination of Acorda’s tozadenant due to severe safety issues.
The failure of tozadenant is a huge setback to Acorda. If it had been approved, it would have been the first new class of drug approved in the US for the improvement of motor symptoms in PD in more than 20 years, and would have brought obvious financial rewards for the company.
This failure with tozadenant is not Acorda’s only issue. In March 2017, the company lost a legal battle over a patent for its key revenue-driver, Ampyra (dalfampridine), the $500M multiple sclerosis drug that makes up 95% of Acorda’s current revenues. The court struck down four out of five patents for Ampyra, leaving the company with a single patent covering the drug, which will expire in July 2018.
With generics threatening its top-selling brand, Acorda had been pinning its hopes on tozadenant and Inbrija (an inhaled PD treatment, formerly known as CVT-301) as new revenue drivers. However, the FDA rejected Acorda’s New Drug Application (NDA) for Inbrija in late August 2017 due to manufacturing issues. The withdrawal of tozadenant, coupled with the refusal of Inbrija, have put the company’s restructure plan at risk.
Acorda’s future performance now relies on its ability to resolve the Inbrija issues for a re-submission, leading to an eventual resubmission of the NDA. Whether this will be accepted by the FDA and eventually lead to the approval of the drug will certainly be another big challenge for the company.