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Compared to interferon beta-1a, the reduction of grey matter volume loss was greater in those treated with both doses of the oral S1P receptor modulator across all age groups, including the youngest patients at the highest risk for brain volume loss.
Bruce Cree, MD, PhD, MAS
A post-hoc analysis from the phase 3 RADIANCE Part B trial has been presented at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia, Pennsylvania, ultimately showing that treatment with ozanimod reduced the cortical grey matter volume loss in adults with relapsing multiple sclerosis (MS).1
When compared to interferon beta-1a (Avonex, Biogen), the lessened grey matter volume loss was greater in those treated with both doses—0.92 mg and 0.46 mg—of the oral sphingosine 1-phosphate (S1P) receptor modulator.
Notably, patients were stratified into subgroups by age, and all age groups lost less cortical grey matter than those in the comparator group, including those aged 18 to 25 years, who tended to have greater baseline brain volume, but more active disease. The 18- to 25-year-old group additionally showed a tendency to experience greater whole brain volume loss at both 12 and 24 months, compared with the older groups.
“Brain volume loss and, in particular, grey matter volume loss represents irreversible end organ injury,” study author Bruce Cree, MD, PhD, MAS, professor of Neurology, University of California San Francisco (UCSF) Weill Institute for Neurosciences, and Clinical Research Director, UCSF MS Center, told NeurologyLive®. “The cerebral cortex is the anatomical structure that contains the neurons whose activity gives us the ability to see, feel, hear, speak, and think. Protecting this vital structure from irreversible injury caused by MS has profound implications for helping preserve the very thing that makes us human.”
In total, the analysis included 874 patients, evaluated based on age groups consisting of 18 to 25 years (n = 146), 26 to 34 years (n = 265), and ≥35 years (n = 463), with measurements being recorded at baseline, 12 months, and 24 months.
The most common adverse events (AEs), occurring at a rate of ≥5% and which were higher with ozanimod than interferon beta-1a were: upper respiratory tract infections, urinary tract infections, and increases of alanine aminotransferase and gamma-glutamyltransferase.
“The important finding is that patients benefitted from treatment in regard to prevention of grey matter loss regardless of age group,” Cree explained. “That the youngest group of patients appeared to benefit the most from treatment deserves follow up. If replicated, this observation implies that early intervention will provide the greatest benefit from brain injury caused by MS.”
Cree also noted that halting grey matter loss early in MS is believed to possibly aid in the prevention of long-term disability and cognitive impairment.
“The goal of treatment is not simply relapse prevention,” he said. “Treatment with highly effective medications early on has the potential to profoundly benefit our patients in the long-term by preserving brain tissue that would otherwise be lost up the erosive impact of MS.”
Just 2 months ago, Celgene submitted a new drug application (NDA) to the FDA for ozanimod, with the RADIANCE trial, along with the SUNBEAM trial, being utilized to support the application. It was additionally submitted to the European Medicines Agency earlier in March.2
In previously announced findings from the initial RADIANCE trial, ozanimod was evaluated in 258 participants randomly assigned to either placebo (n = 88), 0.5-mg ozanimod (n = 87), or 1-mg ozanimod (n = 83). Ultimately, the mean cumulative number of gadolinium-enhancing (Gd+) lesions at weeks 12 to 24 was 11.1 (standard deviation [SD], 29.9) in the placebo group in comparison to only 1.5 (3.7) in the 0.5-mg dose group (odds ratio [OR], 0.16; 95% CI, 0.08 to 0.30; P <.0001) and 1.5 (SD, 3.4) in the 1-mg dose group (OR, 0.11; 95% CI, 0.06 to 0.21; P <.0001).3
Additionally, in early 2017, Celgene announced positive topline data from SUNBEAM, which also assessed 1-mg and 0.5-mg doses of ozanimod in 1346 patients with MS, in comparison with weekly interferon beta-1a. It revealed that both the ozanimod treatment arms demonstrated statistically significant and clinically meaningful improvements compared with interferon beta-1a in annualized relapse rate and a number of secondary end points, including the number of Gd+ lesions and the number of new or enlarging T2 MRI lesions at 1 year.4
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1. Analysis Showed Oral Ozanimod Reduced Brain Volume Loss Across All Age Subgroups in Adults with Relapsing Multiple Sclerosis [press release]. Summit, NJ: Celgene; Published May 7, 2019. apnews.com/Business%20Wire/cd56ea43fff5465683d1491a2d951217. Accessed May 8, 2019.
2. Celgene Submits Application to FDA for Ozanimod for the Treatment of Relapsing Forms of Multiple Sclerosis [press release]. Summit, NJ: Celgene; Published March 25, 2019. businesswire.com/news/home/20190325005794/en. Accessed May 8, 2019.
3. 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):373-81. doi: 10.1016/S1474-4422(16)00018-1.
4. Celgene Announces Positive Results from Phase III SUNBEAM Trial of Oral Ozanimod in Patients with Relapsing Multiple Sclerosis [press release]. Summit, NJ: Celgene; Published February 17, 2017. ir.celgene.com/press-releases/press-release-details/2017/Celgene-Announces-Positive-Results-from-Phase-III-SUNBEAM-Trial-of-Oral-Ozanimod-in-Patients-with-Relapsing-Multiple-Sclerosis/default.aspx. Accessed May 8, 2019.