Vanda Pharmaceuticals Inc. has presented positive results from the long-term maintenance REPRIEVE (Relapse prevention study in patients with schizophrenia) clinical study at the 2015 American Society of Clinical Pharmacology (ASCP) annual meeting in Miami Beach, Florida.
The REPRIEVE study demonstrated the ability of Fanapt (iloperidone) to prevent relapse or impending relapse in adult patients with schizophrenia as compared to placebo. In the REPRIEVE study, 79.6 per cent of patients treated with Fanapt remained relapse free compared to 36.6 per cent for placebo-treated patients. Vanda intends to file a supplemental New Drug Application (sNDA) for Fanapt with the US Food and Drug Administration (FDA) in the second half of 2015 to include the results from the REPRIEVE study in the Fanapt package insert.
"We are delighted with the results of the REPRIEVE study presented at the ASCP annual meeting," said Mihael H. Polymeropoulos, M.D., Vanda's president and chief executive officer. "We believe these results underscore the potential benefits of Fanapt as a treatment alternative for adult patients living with schizophrenia."
The REPRIEVE study was a randomized, double-blind, placebo-controlled study to evaluate prevention of relapse in adult patients with schizophrenia receiving either flexible dose Fanapt or placebo. Study subjects were adults with schizophrenia titrated up to 12 mg/day given as 6 mg BID with open-label Fanapt and then stabilized for a further 14-24 weeks with a flexible dose Fanapt regimen (range between 8-24 mg/day daily dose given BID) as per investigator judgment. Subjects who remained clinically stable for at least 12 weeks entered the relapse prevention phase and were randomized 1:1 to either continue on the same flexible dose regimen of Fanapt or to withdraw from Fanapt to matched placebo in a double-blinded fashion. Subjects were followed for up to 26 weeks and were withdrawn upon showing signs of relapse or impending relapse. A predefined unblinded interim analysis was conducted after 68 relapse or impending relapse events were observed. The primary outcome was time-to-relapse or impending relapse using the interim analysis population.
Of the 587 patients entering the stabilization phase, 195 (33 per cent) met the criteria for the double-blind relapse prevention phase, with 99 subjects randomized to continue with Fanapt and 96 to switch to placebo. The study was stopped early after 68 events were observed and confirmed the hypothesis that Fanapt was more effective than placebo in relapse preventions (log rank test: P < .0001), with a Cox regression hazard ratio estimate of 4.7 (95 per cent confidence interval: 2.7-8.3) favouring Fanapt. The percentage of Fanapt patients remaining relapse free at the end of the double-blind relapse prevention phase was of 79.6 per cent (the Kaplan-Meier estimate (KM estimate)) compared to 36.6 per cent for placebo-treated patients. The mean time to relapse based on KM estimates was 71 days for placebo and 139 days for Fanapt subjects. The most common treatment-emergent adverse events (TEAEs) (>= 5 per cent) suspected to be related to Fanapt in the stabilization phase were dizziness, somnolence (or sleepiness), and dry mouth. There were no Fanapt treatment-related TEAEs with a frequency >2 per cent and higher than placebo in the double-blind relapse prevention phase.
Fanapt is an atypical antipsychotic agent indicated for the treatment of schizophrenia in adults. In choosing among treatments, prescribers should consider the ability of Fanapt to prolong the QT interval and the use of other drugs first. Prescribers should also consider the need to titrate Fanapt slowly to avoid orthostatic hypotension, which may lead to delayed effectiveness compared to some other drugs that do not require similar titration.
Vanda Pharmaceuticals Inc. is a biopharmaceutical company focused on the development and commercialization of products for the treatment of central nervous system disorders.