An ad hoc analysis of patients from a pair of phase 3 clinical trials and an open-label extension suggest that more than 5 years of treatment with ozanimod (Zeposia; BMS) was safe, without differences in age groups.
Findings of an ad hoc analysis of data from the phase 3 SUNBEAM (NCT02294058) and RADIANCE (NCT02047734) clinical trials, as well as the open-label extension DAYBREAK (NCT02576717), suggest that regardless of age, patients with relapsing multiple sclerosis (MS) who were treated with ozanimod (Zeposia; BMS) reported stable or improved clinical and radiologic measures of disease activity over a 6- to 7-year treatment period.1 Additionally, these patients reported no new adverse events (AEs), confirming that long-term treatment is safe and well-tolerated.2
Regardless of patient age group, the adjusted annualized relapse rate (ARR) in the phase 3 trials was less than 0.2, and it remained similarly low in the DAYBREAK extension trial. Additionally, the adjusted mean number of Gadolinium-enhancing lesions per scan remained stable, or decreased, regardless of age category. The adjusted mean number of new/enlarging T2 lesions per scan relative to the DAYBREAK baseline also either remained stable or decreased among those treated with continuous ozanimod, regardless of age.1
The data were presented in 2 posters at the 2023 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 23-25, San Diego, California. The first poster, on efficacy, was presented by Bruce Cree, MD, PhD, MAS, FAAN, professor of clinical neurology, University of California, San Francisco (USCF) Weill Institute for Neurosciences, and clinical research director, UCSF Multiple Sclerosis and Neuroinflammation Center.1 The second, on safety, was presented by Krzysztof Selmaj, MD, professor of neurology at the Medical Academy of Lodz.2
In SUNBEAM and RADIANCE, adults with relapsing MS received oral ozanimod 0.46 mg or 0.92 mg per day or intramuscular interferon beta-1a 30 µg per week for at least 12 months (in SUNBEAM) or 24 months (in RADIANCE). Upon entering the open-label DAYBREAK trial, patients received ozanimod 0.92 mg per day.
Patients in the analysis were divvied into multiple age groups: those aged 25 or younger, those aged 26 to 35 years, those aged 36 to 49 years, and those 50 years and older. All told, the analysis included 2257 patients from the intent-to-treat population of the phase 3 trials, of whom 760 were treated with continuous ozanimod 0.92 mg (≤25 years, n = 118; >25 to ≤35 years, n = 268; >35 to ≤49 years, n = 312; ≥50 years, n = 62).1 Of those patients receiving at least 1 dose of ozanimod in the extension, the mean exposure was 56.1 months (range, 0.03‒72.93) during DAYBREAK.2
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Additional efficacy findings showed that the proportion of those who were free of Gadolinium-enhancing lesions also either remained stable or increased in each age category over 6-7 years of continuous ozanimod treatment. In total, upward of 74% of those treated with ozanimod were Gadolinium-enhancing lesion-free.
“The proportion of patients who were free of new/enlarging T2 lesions relative to [DAYBREAK] baseline remained relatively stable in each age category throughout the [open-label extension] in patients treated with continuous ozanimod. “Patients in the 50 [years or older] age group had a numerically lower adjusted ARR and less [Gadolinium-enhancing] and new/enlarging T2 lesions per scan and were generally more likely to be [Gadolinium-enhancing] lesion free or free from new/enlarging T2 lesions than the 25 [years or younger] age group,” Cree and colleagues wrote.1
As for safety, Selmaj and colleagues reported that the rate of treatment-emergent AEs increased with age among those treated continuously with ozanimod, discontinuation rates because of these AEs were low (≤6.1%) across all age and treatment groups. “During parent trials and [open-label extension], most individual [treatment-emergent] AE preferred terms showed no specific age-related pattern of occurrence, except [that] more patients 35 [years or older] had respiratory or viral respiratory infections vs those 35 years or [younger],” Selmaj et al wrote.2
Otherwise, cataract was reported only among those older than 35 years; urinary tract infections were most common among those 50 years or older; and hypercholesterolemia, hypertension, back pain, falls, and gamma glutamyltransferase increases were more common with the older age groups. Similarly, the proportion of patients with any cardiac disorder or neoplasm (benign/malignant/unspecified) treatment-emergent AEs increased with age among those treated with continuous ozanimod.
Overall serious AE rates during the DAYBREAK extension increased with age, with ranges from 9%-12% in those 35 years or younger to 23%-29% in those 50 years or older. Although, Selmaj and colleagues noted that no apparent age-related pattern appeared for specific serious AE-preferred terms. “Serious infections during the parent trials and DAYBREAK showed no association with age (<6% in all age groups). Across all age groups, [interferon] was associated with more TEAEs and flu-like symptoms during the parent trials compared with those who continuously received ozanimod 0.92 mg,” they wrote.
Previous analyses have shown similarly positive results with long-term use of ozanimod in clinical trials. In a post hoc analysis of RADIANCE and DAYBREAK, a higher proportion of patients with relapsing MS achieved no evidence of disease activity status 3 or 4 (NEDA-3 and NEDA-4) following treatment with oral ozanimod vs intramuscular interferon beta-1a.3 At months 12 and 24 of RADIANCE, investigators observed NEDA-3 rates of 31.2% and 24.6% (P <.05) for ozanimod-treated patients vs 26.9% and 17.0% for those on IFN, respectively. In DAYBREAK, rates were 16.2% (P <.05), 13.4% (P <.05), and 10.7% with continuous ozanimod at months 12, 24, and 36, respectively, compared with rates of 9.8%, 8.6%, and 7.4% for those on/transitioned from IFN.
Those findings were presented by lead investigator Ludwig Kappos, MD, professor of neurology at University Hospital Basel, Switzerland, who told NeurologyLive® at the time, “We see the effects in the first year were repeated over time, and that a significant number of patients remained disease activity free under these quite strict criteria. Those who had evidence of disease activity mainly had this through MRIs, so through lesions that occurred in their regularly repeated and standardized assessments."
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