Recent studies show efficacy and safety for both lemborexant and ozanimod.
Russell Rosenberg, PhD
Recently, both Eisai, with its launch of lemborexant (Dayvigo), and Bristol Myers Squibb, with its launch of ozanimod (Zeposia), have announced the availability of their respective newly US Food and Drug Administration (FDA) approved agents.
Lemborexant was approved for the treatment of insomnia in adults in late December 2019. The drug, which will be available in 5- and 10-mg doses, is a small molecule orexin receptor antagonist that binds to both orexin receptor 1 and 2.
"Given up to 30% of adults worldwide report insomnia symptoms and the increase in sleep problems due to the life changes caused by the COVID-19 pandemic environment, it is crucial to offer patients treatment options that may help them fall asleep and stay asleep," Russell Rosenberg, PhD, D.ABSM, principal investigator, and former Chairman of the Board, National Sleep Foundation, said in a statement. "Dayvigo may be an appropriate treatment option for some of these patients."
The approval of lemborexant was decided based on data from 2 pivotal phase 3 studies, SUNRISE 1 and SUNRISE 2, that assessed lemborexant versus placebo for 1 and 6 months.
In SUNRISE 1, lemborexant demonstrated statistically significant superiority over placebo on the primary end point, which was mean change in log-transformed latency to persistent sleep (LPS) from baseline to end of treatment for both doses.
Treatment with the study drug also demonstrated statistically significant improvements in sleep efficiency and wake after sleep onset compared with placebo.
As well, lemborexant was also statistically superior to placebo on the secondary end points in SUNRISE 2, including change from baseline to end of treatment on patient-reported sleep efficiency and wake after sleep onset.
The most common adverse events reported in SUNRISE 1 and SUNRISE 2 was somnolence (10 mg, 10%; 5 mg, 7%; placebo, 1.0%). The most common adverse events leading to discontinuation of lemborexant were somnolence (10 mg, 1.0%; 5 mg, 0.7%; placebo, 0.4%) and nightmares (10 mg, 0.3%; 5 mg, 0.3%; and placebo, 0%).
Ozanimod, on the other hand, was given the regulatory go-ahead in late March 2020, for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. It is an oral sphingosine-1-phosphate (S1P) receptor modulator.
Ozanimod’s approval was supported by data from the phase 3 SUNBEAM and RADIANCE part B trials that included more than 2600 adults with MS. The studies compared ozanimod to interferon beta-1a on the primary end point of annualized relapse rate (ARR).
In total, 1346 patients with RMS were randomly assigned to either 1.0 mg (n = 447) or 0.5 mg (n = 451) of ozanimod or IFN-ß1a (n = 448).
Over a 12-month treatment period, the adjusted ARR were 0.35 (95% CI, 0.28—0.44) for IFN-ß1a compared with 0.18 (95% CI, 0.14–0.24) for the ozanimod 1.0-mg group and 0.24 (95% CI, 0.19–0.31) for the 0.5-mg group, for respective rate ratios of 0.52 (95% CI, 0.41–0.66; P <.0001) and 0.69 (95% CI, 0.55—0.86; P = .0013).
Ozanimod was generally well-tolerated, with about 3% of patients treated with the study drug discontinuing due to adverse events (AEs). Serious AEs occurred in 2.9% (n = 13) in the 1.0-mg group, 3.5% (n = 16) in the 0.5-mg group, and 2.5% (n = 11) in the IFN-ß1a group.
No serious opportunistic infections occurred in ozanimod-treated participants. In addition to reduced ARR, treatment with ozanimod was associated with a 63% relative reduction of T1-weighted gadolinium-enhanced lesions, and a 48% relative reduction in new or enlarging T2 lesions at 1 year in SUNBEAM.
Similar reductions were also observed at 2 years in RADIANCE. Notably, there was no significant difference in confirmed disability progression between the 2 study drugs at 3 and 6 months.