Shares in Acorda Therapeutics are on the slide following the news that the company’s Parkinson’s drug tozadenant has been linked to a serious and potentially fatal side effect.
The New York biotech confirmed today that seven patients in its phase 3 program for tozadenant have developed agranulocytosis—a steep decline in white blood cells—that is “possibly drug-related” and in some cases has resulted in sepsis with five deaths.
Shares in the company were down more than one third in after-hours trading at the time of writing, as investors tried to gauge the seriousness of the situation and the potential impact on tozadenant’s prospects.
CEO Ron Cohen said the company is still hoping to report results in the first quarter of 2018—depending on feedback from the FDA and the data and safety monitoring board overseeing its phase 3 trials. However, it intends to step up safety monitoring in its phase 3 program for the drug, carrying out blood cell count checks every week, and has paused enrollment in long-term safety studies.
Tozadenant is an oral adenosine A2a receptor antagonist designed to tackle "off" times among Parkinson's patients taking the standard levodopa/carbidopa treatment. The drug was acquired by Acorda when it bought Finnish biotech Biotie last year for $363 million.
Acorda has previously said that that tozadenant could become a $400 million product if approved for this indication, with the potential to become the first new class of drug approved for the treatment of Parkinson's in the U.S. in more than 20 years. Possible upside could also come if experimental data suggesting it can protect the dopamine-producing cells that are destroyed in Parkinson’s is backed up in further studies.
It’s not the first A2a receptor drug to run into trouble in Parkinson’s disease. Merck & Co had to scrap its preladenant candidate in 2010 after it failed to show an improvement over placebo in late-stage testing, while Vernalis and Biogen abandoned their phase 2 candidate vipadenant after toxicity issues emerged. Acorda said on a conference call that agranulocytosis has not been seen with other A2a drugs to date.
Tozadenant is a companion drug to Acorda’s CVT-301, an inhaled formulation of levodopa which was filed for approval earlier this year after phase 3 results which analysts said gave it a 90% chance of approval, and which the company reckons could make it a $500 million product at peak.
CVT-301 is also intended for patients suffering "off" episodes, when Parkinson’s symptoms reappear despite adhering to the oral treatment.
Acorda suffered another pipeline setback last year when it was forced to abandon studies of dalfampridine for poststroke walking difficulties, causing it to cut staff and refocus its attention on CVT-301 and tozadenant.
Analysts at Jefferies said that investors would likely remove the tozadenant program from the pipeline valuation, and that the company's valuation is fair based on the prospects for CVT-301.
"We assume the risk/benefit of this drug is hampered for approval at this point," they said, although Acorda maintains that the drug could still be OK if it demonstrates good efficacy given the serious problems affecting the patient population.
"Even if [the data] is positive and good - it's a regulatory question for FDA now, and ...even if approved, it would likely have major warnings or restrictions (weekly monitoring, etc.) on the label which could hamper commercial uptake," the analysts conclude.