ALKS 3831 appears safe, well tolerated as long-term schizophrenia treatment
A combination of olanzapine and samidorphan was well tolerated and not associated with new safety risks compared with olanzapine alone, according to data presented during the Virtual 2020 Schizophrenia International Research Society Congress.
Researchers collected the data as part of the ENLIGHTEN-2 extension study, which also showed a stabilized weight and metabolic laboratory parameter profile that appeared to support long-term use of the treatment, ALKS 3831 (Alkermes).
“Because schizophrenia is a lifelong disease, long-term safety and tolerability is an important consideration,” Adam Simmons, MPH, director of clinical program management at Alkermes, told Healio Psychiatry. “We previously evaluated the safety and efficacy of ALKS 3831 up to 6 months in ENLIGHTEN-2. Our objective with the ENLIGHTEN-2 extension study was to evaluate the longer-term safety and tolerability of ALKS 3831 among people with schizophrenia.”
To do so, Simmons and colleagues administered at least one dose of open-label ALKS 3831, which combines olanzapine with the opioid receptor antagonist samidorphan to mitigate weight gain, to 265 patients (mean age, 40.7 years; 72.5% men; 70.6% black) with a DSM-5 diagnosis of schizophrenia who completed the ENLIGHTEN-2 study within the previous 7 days. Patients who entered the extension study received the equivalent dose of olanzapine they were on at the conclusion of ENLIGHTEN-2, and then investigators administered olanzapine/samidorphan as daily doses of either 10 mg/10 mg, 15 mg/10 mg or 20 mg/10 mg. Researchers assessed safety through adverse event monitoring, weight and waist circumference measurements and clinical laboratory testing. They evaluated psychiatric symptoms using Positive and Negative Syndrome Scale (PANSS) total scores and the Clinical Global Impression of Severity (CGI-S) scale.
A total of 167 extension participants completed the 52-week treatment period. Fifteen patients (5.7%) discontinued treatment due to adverse events.
Results showed most adverse events were mild or moderate in severity, with 2.6% of patients having a severe adverse event. The most common adverse events were decreased weight (8.7%), extra dose administered (7.9%), headache (6.8%) and increased weight (6%). The researchers reported seven serious adverse events among 1.9% of patients. These included two of schizophrenia and one each of alcoholic gastritis, agitation, psychotic disorder, acute kidney injury and pulmonary embolism. No deaths occurred during the study.
The mean overall change from baseline in body weight was 0.03 kg, which represented a mean percentage change of 0.05%. Patients who received olanzapine in ENLIGHTEN-2 and switched to ALKS 3831 in the ENLIGHTEN-2 extension exhibited similar weight gain compared with those who remained on ALKS 3831 throughout both studies, with a mean change in weight from baseline to 52 weeks of less than 1 kg among each group. At baseline, patients’ mean waist circumference was 93.6 cm, and at 52 weeks, the mean change from baseline was 0.35 cm. Over the course of the study, fasting lipid and glycemic parameters remained stable, with generally small mean changes from baseline to 52 weeks.
Extension patients had mild to moderate symptoms of schizophrenia managed as an outpatient at study entry, with a mean PANSS total score of 59 overall. Over 52 weeks of ALKS 3831 treatment, PANSS total scores remained stable. Nearly three-quarters of patients maintained CGI-S scores of 3 or less, which represents mild illness, at each study visit.
According to the researchers, study limitations included loss of randomization upon entering the extension study, as well as the single-arm design; missing data and premature discontinuations; and inability to generalize findings to patients experiencing more severe symptoms.
“A significant unmet patient need remains in schizophrenia despite the number of treatment options available today,” Simmons told Healio Psychiatry. “The results of this long-term study provide further data for the evaluation of the safety and efficacy of this investigational medication for the treatment of schizophrenia and bipolar 1 disorder.” – by Joe Gramigna
Kahn R, et al. Poster #T35. Presented at: Virtual 2020 Schizophrenia International Research Society Congress.
Disclosures: Simmons and eight other study authors report being employees of Alkermes Inc. during the conduct of the study. Please see the study for all other authors’ relevant financial disclosures.