After respective approvals in December 2019 and March 2020, lemborexant (Dayvigo; Eisai) and ozanimod (Zeposia; Bristol Myers Squibb) have become available for patients with insomnia and multiple sclerosis.
Russell Rosenberg, PhD, D.ABSM
Early this month, 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 FDA-approved agents.1,2
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 2.1
"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," said Russell Rosenberg, PhD, D.ABSM, principal investigator, and former Chairman of the Board, National Sleep Foundation, 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.3,4
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. In SUNRISE 2, it was also observed to be statistically significantly superior on the primary end point, which was mean change from baseline to end of treatment at 6 months for log-transformed, patient-reported sleep onset latency compared to 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%).
"The U.S. is the first country in which DAYVIGO is available, and we are excited by its potential to help patients sleep better," said Ivan Cheung, Chairman, and Global President, Neurology Business Group, Eisai, in a statement. "DAYVIGO is an important addition to Eisai's rapidly growing neurology portfolio, which underscores our leadership in neuroscience. Eisai remains committed to discovering and developing innovative solutions to unmet medical needs that benefit patients and their families."
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.2
“We are pleased to now bring Zeposia, an important new once daily treatment option, to RMS patients,” said Tina Deignan, PhD, vice president, and US head of immunology, Bristol Myers Squibb, in a statement. “Zeposia is the first and only S1P that requires no first dose observation, which may minimize the number of interactions relapsing MS patients need to have with healthcare practitioners prior to initiating therapy during this unprecedented time of social distancing.”
Ozanimod’s approval was supported by data from the phase 3 SUNBEAM (NCT02294058) and RADIANCE part B (NCT01628393) trials that included more than 2600 adults with MS. The studies compared ozanimod to interferon beta-1a (IFN-ß1a; Avonex) on the primary end point of annualized relapse rate (ARR).5
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
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.6
1. Eisai Announces U.S. Availability of DAYVIGO™ (lemborexant) CIV, a New Treatment Option for Adults With Insomnia [news release]. Woodcliff Lake, NJ: Eisai Inc; Published June 1, 2020. Accessed June 8, 2020. eisai.mediaroom.com/2020-06-01-Eisai-Announces-U-S-Availability-of-DAYVIGO-TM-lemborexant-CIV-a-New-Treatment-Option-for-Adults-With-Insomnia
2. Bristol Myers Squibb Announces Commercial Launch and Availability of ZEPOSIA® (ozanimod), a New Oral Treatment for Relapsing Forms of Multiple Sclerosis [news release]. Princeton, NJ; Published June 1, 2020. Accessed June 8, 2020. news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-commercial-launch-and-availabil
3. US FDA approved Eisai’s Dayvigo (lemborexant) for the treatment of insomnia in adult patients [news release]. Woodcliff Lake, NJ: Eisai Inc; Published December 23, 2019. Accessed June 8, 2020. eisai.mediaroom.com/2019-12-23-U-S-FDA-Approves-Eisais-DAYVIGO-TM-lemborexant-for-the-Treatment-of-Insomnia-in-Adult-Patients.
4. Yardley J, Kärppä M, Inoue Y, et al. Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: 12-month results from SUNRISE- Presented at: World Sleep 2019; September 20-25; Vancouver, BC, Canada. Abstract 1663.
5. Comi G, Kappos L, Selmaj KW, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomized, minimum 12-month, phase 3 trial. Lancet Neurol. Published online September 3, 2019. doi: 10.1016/S1474-4422(19)30239-X.
6. Cohen JA, Arnold DL, Comi G, et al. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):373-381. doi: 10.1016/S1474-4422(16)00018-1.