Waist circumference also less with combo
SAN DIEGO — Olanzapine is a very effective atypical antipsychotic for treatment of schizophrenia, but — and this is a major barrier to adherence with this drug — it triggers weight gain, often more than 7% of body weight, which then drives a number of comorbidities.
An investigational agent, ALKS 3831, which combines olanzapine with samidorphan, demonstrated clinical efficacy in the ENLIGHTEN-1 pivotal trial, but beyond efficacy the developers of ALKS 3831 believed that samidorphan would blunt the weight gain seen with olanzapine.
Against that background, the findings from the ENLIGHTEN-2 study are reassuring: for weight gain, mean change from baseline at week 24 was 4.21% in the ALKS 3831 treated patients versus 6.59% for olanzapine treated patients, which was difference of −2.38% and was significant (P=0.003), said Adam Simmons, MPH, director of clinical program management at Alkermes, which is developing ALKS 3831. Simmons presented the ENLIGHTEN-2 findings in a poster at Psych Congress 2019.
Additionally, the proportion of patients who gained 10% or more of baseline weight at week 24 was 17.8% in the combination arm versus 29.9% in the olanzapine arm, a difference that was also statistically significant, he said.
“What appears to be happening is there is an initial weight gain with either treatment, but with ALKS 3831 that gain plateaus after week 8, while weight gain continues with olanzapine,” Simmons told BreakingMED.
“ALKS 3831 also attenuates the waist circumference increases observed with olanzapine, and in this case the difference is apparent from the initiation of treatment,” he said. At week 1, the difference was significant at P <0.05, and by week 25 the difference was significant at P <0.001.
Waist circumference is a significant predictor of cardiovascular risk — cardiovascular disease is the leading cause of death in persons with schizophrenia — thus it was perplexing that metabolic measures of lipids, triglycerides, and hemoglobin A1c were small in both arms, and not significantly different, Simmons said, noting that this is an area that will continue to be studied.
The initial study randomized 550 patients— 274 to ALKS 3831 and 275 to olanzapine. The analysis included data from 352 patients who completed the study.
An extension study (ENLIGHTEN-2 EXT) is currently ongoing, Simmons noted.
Simmons said the company plans to submit the combo drug to the FDA by the end of 2019.
Written by Peggy Peck, Editor-in-Chief, BreakingMED, is a service of @Point of Care, LLC, which provides daily medical news reports curated to serve the unique needs of busy physicians and other healthcare professionals.