A phase 2 clinical trial of Concert Pharmaceuticals’ CTP-692 in schizophrenia patients has missed its primary endpoint. The setback led Concert to stop development of the deuterated form of D-serine and focus on a phase 3 treatment for a form of hair loss.
Concert moved CTP-692 into phase 2 as an adjunctive treatment for schizophrenia on the strength of evidence that D-serine, a co-agonist at the NMDA glutamate receptor, improves outcomes in people with the condition. Schizophrenia patients have low levels of D-serine, and studies have linked the molecule to effects on symptoms and cognition. However, renal safety is an issue with D-serine.
CTP-692, deuterated D-serine, was designed to improve on the renal safety and brain exposure of the amino acid. Yet, having come through a phase 1 study, the drug candidate has come unstuck in phase 2.
Investigators randomized 325 schizophrenia patients, all of whom already were on a stable course of an antipsychotic medication at baseline, to receive one of three doses of CTP-692 or placebo once a day.
After 12 weeks, patients on CTP-692 statistically performed no better on the Positive and Negative Syndrome Scale (PANSS) than their peers on placebo did, causing the study to miss its primary endpoint. All evaluated doses of CTP-692 were similarly ineffective on positive or negative symptoms subscales of PANSS.
Concert was upfront about the failure in its statement and has acted decisively in response to the data. The phase 2 failure marks the end of the line for CTP-692.
“The body of evidence in the field supporting D-serine as an adjunctive treatment for schizophrenia was compelling and led us to advance CTP-692 into a phase 2 proof of concept study. Unfortunately, we didn’t see the results we hoped for to support continuation of this program,” Concert CEO Roger Tung, Ph.D., said in a statement.
Concert’s focus is now on a phase 3 clinical trial that is evaluating CTP-543, an oral inhibitor of JAK1 and JAK2, in adults with moderate to severe alopecia areata. The 700-subject phase 3 clinical trial is currently enrolling patients to assess the effect of CTP-543 on a disease severity scale.
Shares in Concert fell almost 50% in premarket trading.