On 1 February, Concert Pharmaceuticals announced it was stopping development of its adjunctive treatment for schizophrenia, CTP-692 (D-serine) after it failed to meet its primary endpoint and other secondary endpoints in a Phase II trial.
The double-blind, randomised, placebo-controlled trial was conducted in 325 patients and failed to demonstrate significant improvement compared to placebo for any of the doses of CTP-692 used in the trial (1g, 2g, or 4g once daily), measured by the change in the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks compared to baseline. Furthermore, no significant improvements were seen in the PANSS positive or negative symptoms subscales.
One key unmet need in the schizophrenia market is for drugs with improved safety profiles. While there is evidence in the literature that D-serine can improve outcomes in patients with schizophrenia as adjunctive therapy, it is associated with renal safety issues. CTP-692 was designed to improve upon the renal safety issues, so CTP-692’s failure to demonstrate efficacy in the Phase II trial is especially disappointing given that the majority of adverse effects reported in the trial were mild in severity and equally distributed across the different CTP-692 dose and placebo groups.
Cognitive impairments are common in schizophrenia patients and contribute significantly to the disability of the disease, as these symptoms persist during periods of remission. Although there is a high number of established atypical antipsychotic products on the schizophrenia market, they are only able to effectively manage the positive symptoms of the disorder. Therefore, there is a high unmet need for effective therapies to treat cognitive impairments associated with schizophrenia.
Because D-serine has been linked to having effects on cognition, it was hoped that CTP-692 would demonstrate a positive effect on cognitive impairment along with efficacy. CTP-692’s failure in the trial leaves the market open for therapies that treat cognitive impairment associated with schizophrenia. The approval of any such drug would likely to lead to a large uptake of patients.
Concert Pharmaceuticals’ shares fell almost 50% after discontinuing CTP-692, one of its two pipeline assets. The company will now be focused on its remaining pipeline product, CTP-543, which is being investigated as a treatment for alopecia areata.
CTP-543 is currently in Phase III development in the US, having shown promising results in Phase II trials. Last year, Concert Pharmaceuticals announced that patients treated with CTP-543 showed continued maintenance of hair growth in a long-term extension study following its Phase II trial. GlobalData forecasts that CTP-543 will have annual revenue of $228M by 2026 in the US.