Alkermes announces Vibrance-1 study meets primary endpoint

Alkermes (ALKS) announced detailed results from the Vibrance-1 phase 2 study evaluating alixorexton in patients with narcolepsy type 1. Alixorexton, formerly ALKS 2680, is a novel, investigational, oral, selective orexin 2 receptor agonist in phase 2 development as a once-daily treatment for NT1, narcolepsy type 2 and idiopathic hypersomnia. The randomized, placebo-controlled, six-week, double-blind phase 2 study conducted in 92 patients with NT1 demonstrated clinically meaningful and statistically significant improvements in wakefulness, cognition and fatigue that were sustained over the six-week treatment period. Alixorexton was generally well tolerated at all doses tested. The data were presented in three oral presentations at World Sleep Congress, taking place Sept. 5-10 in Singapore. Once-daily alixorexton met the primary endpoint across all doses tested, demonstrating statistically significant, clinically meaningful and dose-dependent improvements from baseline compared to placebo in mean sleep latency on the Maintenance of Wakefulness Test at week six. Patients had a mean sleep latency of approximately 3 minutes at baseline. All alixorexton dose groups achieved normative wakefulness on the MWT, with observed mean sleep latency of approximately 24 minutes, 26 minutes and 28 minutes for the 4, 6 and 8 mg doses, respectively. Alixorexton demonstrated clinically meaningful improvements on the key secondary endpoint evaluating change from baseline versus placebo on the Epworth Sleepiness Scale at week six. Patients had a mean ESS score of 18.5 at baseline. Improvements in ESS were sustained in the normal range for all doses tested across all timepoints during the six-week double-blind treatment period and the subsequent open-label extension period through week 13. On the key secondary endpoint evaluating mean weekly cataplexy rates, alixorexton demonstrated numerical and clinically meaningful improvements across all doses compared to placebo at weeks five and six and, on the pre-specified analysis, achieved statistical significance at the 6 mg dose. More than 40% of patients at the 6 mg and 8 mg doses achieved 100% reduction in cataplexy during week six of the study. Vibrance-1 also included a range of exploratory patient-reported outcome measures. Alixorexton drove statistically significant and clinically meaningful improvements from baseline compared to placebo in disease severity, fatigue and cognitive impairment. At week six, most patients receiving alixorexton reported mild narcolepsy severity. Across all timepoints and all alixorexton dose groups, mean cognitive impairment scores fell within the lowest severity category of “none or minimal” impairment and mean fatigue scores fell into the “normal” range-effectively achieving normalization across both cognition and fatigue. Alixorexton was generally well tolerated across all doses tested throughout the six-week, randomized, double-blind treatment period. No serious treatment-emergent adverse events were reported. There were no clinically meaningful changes in hepatic and renal parameters, vital signs, ECGs or ophthalmic exams in the alixorexton-treated group. Most TEAEs were mild to moderate in severity. The most common TEAEs7 were pollakiuria, insomnia, salivary hypersecretion, urinary urgency and blurred vision. Events of insomnia largely occurred and resolved within the first week of dosing. Events of blurred vision were mostly mild and intermittent and largely occurred and resolved within the first three days of treatment. More than 95% of patients who participated in the six-week double-blind portion of the trial entered into the seven-week open-label extension. Based on these results, Alkermes plans to initiate a global phase 3 program for alixorexton in the first quarter of 2026. Vibrance-2, a phase 2 study evaluating the safety and efficacy of alixorexton in adults with NT2, recently completed enrollment. Vibrance-3, a phase 2 study evaluating the safety and efficacy of alixorexton in adults with IH, is currently enrolling.