Targacept's investigational neuronal nicotinic receptor agonist has failed to meet its primary endpoint in a Phase II trial in adults with attention deficit hyperactivity disorder. Datamonitor expects that future development focus for TC-5619 will shift towards schizophrenia, in view of Phase II data demonstrating efficacy in the treatment of cognitive dysfunction associated with the condition.
Results from the Phase II study showed that TC-5619 (Targacept) failed to meet the primary efficacy outcome measure - change from baseline on a commonly used attention deficit hyperactivity disorder (ADHD) rating scale - after four, eight, and 12 weeks of dosing. Nevertheless, the candidate was generally well tolerated in the trial, with no serious adverse events reported. Analyses of the full dataset from the ADHD trial are ongoing.
Stimulant medications such as methylphenidate form the mainstay of treatment of ADHD. As a neuronal nicotinic receptor (NNR) agonist, TC-5619 represents a non-stimulant drug and a novel approach to the treatment of ADHD. Indeed, Datamonitor believes that NNR agonists have the potential to satisfy the unmet need for more efficacious medications for the estimated 20% of patients who do not respond to stimulant drugs. Based upon Datamonitor's estimation of the size of the diagnosed ADHD population, this equates to a population of between 4.3 million and 5.1 million patients who are unresponsive to stimulant treatments in the US.
With developers keen to tap into the non-stimulant segment of the ADHD market, Targacept is not the only company with an interest in the NNR drug class. Abbott's and NeuroSearch's NNR agonist ABT-894 (sofinicline) is also in Phase II development for adult ADHD. Unlike TC-5619, ABT-894 has demonstrated positive Phase II data in adults with ADHD, with the drug's efficacy reported to be comparable to that of Strattera (atomoxetine; Eli Lilly), the first non-stimulant drug approved for ADHD. ABT-894 has also been shown to be safe and well tolerated. Should it reach the market, Datamonitor forecasts that the drug will achieve revenues in excess of $300m across the seven major markets (the US, Japan, France, Germany, Italy, Spain, and the UK) by 2018.
The failure of Targacept's TC-5619 to meet its primary endpoint in an ADHD trial does not signal the end the candidate's clinical development. The drug is also in Phase II trials for the potential treatment of cognitive dysfunction in schizophrenia and Phase I trials for Alzheimer's disease. Datamonitor expects that Targacept's late-stage development of TC-5619 will shift towards the schizophrenia population in view of positive top-line results from a Phase II trial assessing the drug as an augmentation therapy to improve cognition in patients with schizophrenia.