Both long-acting injectable treatments produced statistically significant and clinically meaningful improvements.
Jelena Kunovac, MD, MS
Topline results from the ALPINE study of aripiprazole lauroxil (Aristada) and paliperidone palmitate (Invega Sustenna) demonstrate comparable 6-month efficacy in controlling symptoms of schizophrenia. Both long-acting injectable treatments produced statistically significant and clinically meaningful improvements in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to week 4, meeting the study’s primary endpoint.
"The ALPINE study showed that both Aristada, given every 2 months, and Invega Sustenna, given every month, demonstrated statistically significant improvements from baseline in schizophrenia symptoms, and that the efficacy was similar for both medicines throughout the 6-month study,” said Craig Hopkinson, MD, Chief Medical Officer at Alkermes.
Hopkinson added that the results demonstrate that both aripiprazole lauroxil and paliperidone palmitate can help smooth the transition from inpatient facilities to outpatient care, which poses a challenge to many patients with schizophrenia.
"People living with schizophrenia face a complex treatment system and countless challenges that can disrupt continuity of care and make them vulnerable to relapse and re-hospitalization," said Jelena Kunovac, MD, MS, founder and president of Altea Research, and ALPINE study investigator. “The results from ALPINE validate the role that long-acting atypical antipsychotics can play in rapidly and effectively stabilizing patients in the hospital and supporting their continuity of care after discharge.”
The randomized, double-blind, phase 3b ALPINE (Aripiprazole Lauroxil and Paliperidone palmitate: Initiation Effectiveness) study included 200 participants experiencing an acute exacerbation of schizophrenia. Participants were randomized to either the Aristada group, where treatment began with Aristada Initio followed by Aristada 1064 mg every 2 months, or the Invega Sustenna group, where treatment began with a 234 mg loading dose of Invega Sustenna followed by a 156 mg dose each month. According to a company spokesperson, a placebo arm was not included in the study in order to avoid giving patients with schizophrenia a placebo.
At 4 weeks, the reduction in Positive and Negative Syndrome Scale (PANSS) total scores from baseline were -17.4 points (P <0.001) for the Aristada group compared to -20.1 points (P <0.001) for the Invega Sustenna group.
The improvements compared to baseline continued through weeks 9 and 25, meeting prespecified secondary endpoints. For the Aristada and Invega Sustenna groups, the improvements at week 9 were -19.8 points and -22.5 points, and at week 25 they were -23.3 points and -21.7 points, respectively. The improvements in PANSS scores were not statistically different between the Aristada and Invega Sustenna groups at any evaluated time point.
"These data underscore that Aristada Initio along with the 2-month dose of Aristada together represent a novel approach to treatment initiation and a compelling clinical option for patients and healthcare professionals alike,” commented Hopkinson.
On the safety and tolerability outcomes, the study reported that each treatment group had the same 3 most common adverse events. For the Aristada and Invega Sustenna groups, respectively, the adverse events were injection site pain: 17.2% and 24.8%, increase in weight: 9.1% and 16.8%, and akathisia: 9.1% and 10.9%.
Just 56.6% of participants in the Aristada group and 42.6% of those in the Invega Sustenna group completed the 6-month study. However, a company spokesperson noted that the discontinuations were not primarily due to adverse events and added, “the discontinuation rates in the ALPINE study are consistent with those found in other clinical trials for schizophrenia of this duration.”
More detailed study results will be presented at the 2019 Congress of the Schizophrenia International Research Society (SIRS) in Orlando, Florida, and at other medical meetings.