Oral treatment with ozanimod (RPC1063), an investigational immunomodulator under development by Celgene, is better at preventing brain volume loss, compared with Avonex (interferon-beta-1a), in adults with relapsing forms of multiple sclerosis, data from a clinical trial shows.
After two years of treatment, ozanimod was more effective at limiting brain volume loss across all age groups, but especially beneficial for younger patients (18 to 25 years), who were also the ones with the steepest decline in brain volume.
The findings were presented on May 9 at the 2019 American Academy of Neurology (AAN) Annual Meeting, held in Philadelphia, in a poster titled “Gray Matter Volume Loss Is Increased in Younger Patients With Relapsing Multiple Sclerosis but Minimized by Ozanimod: Experience From the Ozanimod Phase 3 Program.”
Celgene completed a two-part Phase 2/3 trial, called RADIANCE (NCT01628393), last year to determine the efficacy, safety and tolerability of two doses of oral ozanimod hydrochloride (0.5 and 1 mg, given once daily) compared to weekly intramuscular Avonex (marketed by Biogen, and injected into the muscle) over two years of treatment.
The study included 1,313 adults with relapsing MS across 150 sites in 21 countries. Patients were between 18 and 55 years old.
The RADIANCE trial was divided into two parts: in part A, patients received either one daily dose of ozanimod (0.5 or 1.0 mg) or a placebo for 24 weeks; in part B, a two-year open-label extension study completed by 223 patients, those initially on placebo switched to ozanimod treatment.
Findings of the extension phase (part B) showed a higher proportion of patients who became free from lesions (areas of active inflammation and disease activity) on MRI scans after two years of treatment — 86.5% with the lower dose and 94.6% with the higher dose.
Pooled data from this study and the prior SUNBEAM trial (NCT02294058), which included 2,659 patients, also showed that ozanimod reduced the number of relapses per year by 42% in the higher dose group, and by 26% in the lower dose group, compared with Avonex.
At the AAN meeting, Celgene presented a posterior analysis of the RADIANCE study, assessing how ozanimod compared with Avonex in preventing brain volume loss, and if this effect varied according to a patient’s age.
Researchers looked at 874 relapsing MS patients, who were divided by age groups: 18 to 25 years (146 patients); 26 to 34 years (265); and 35 and older (463).
Treatment effect on brain volume, including thalamic volume and cortical grey matter, was evaluated by MRI scans at the study’s start, and after one and two years of treatment.
MRI findings showed that patients under 25 had greater brain volume, but more active disease (MRI lesions) at the study’s start. Compared with older patients, these younger participants experienced a greater brain volume loss at one and two years.
After two years of treatment with ozanimod 1 mg, however, patients across all age groups lost less brain volume compared with those given Avonex, and in all brain structures evaluated.
The most frequent adverse reactions in those taking ozanimod were upper respiratory tract infections, urinary tract infections, and increases in alanine aminotransferase (ALT) and in gamma-glutamyl transferase (GGT) — two liver function markers.
“Since loss of brain volume can be associated with disease progression, there is a need for early diagnosis and treatment in multiple sclerosis,” Alise Reicin, MD, president of global clinical development for Celgene, said in a press release.
“This analysis adds to growing evidence supporting the potential use of ozanimod to treat adults with relapsing multiple sclerosis, including the youngest patients studied, who also showed the most rapid loss in brain volume in this study,” Reicin added.
Ozanimod is an oral modulator of sphingosine 1-phosphate (S1P) receptor subtypes 1 (S1P1) and 5 (S1P5). The mechanism by which ozanimod exerts therapeutic effects in MS is unknown, but it is thought to involve the reduction of immune cells (lymphocytes) in the central nervous system — brain and spinal cord — preventing nerve cell damage.
The compound is still under investigation and not approved for any use in any country.
Celgene submitted a New Drug Application in March to the U.S. Food and Drug Administration, and an equivalent application to the European Medicines Agency, seeking marketing approval of ozanimod for the treatment for adults with relapsing MS.