New Orleans, LA— The oral investigational agent ozanimod, which is from the same drug class as fingolimod (Gilenya), may be as effective as fingolimod, with fewer safety concerns, for the treatment of patients with relapsing multiple sclerosis (MS), reported Brett E. Skolnick, PhD, Receptos, San Diego, CA, at the 2017 Consortium of Multiple Sclerosis Centers annual meeting. Dr Skolnick stepped in for the lead investigator Giancarlo Comi, MD, Vita-Salute San Raffaele University, Neurology, Milan, Italy, who was unable to attend the meeting.
Ozanimod, a selective sphingosine-1-phosphate (S1P) receptor-1 and -5 modulator, demonstrated continued efficacy on measures of disease activity in patients with relapsing MS. The unadjusted annualized relapse rate was only 0.17 in the blinded extension study of the phase 2, RADIANCE Part A clinical trial.
The increased receptor selectivity of ozanimod and additional properties are predicted to result in a more favorable safety profile than is seen with other nonselective and selective S1P receptor modulators (ie, fingolimod). Fingolimod is FDA approved for the treatment of patients with relapsing forms of MS, but concerns have been raised about associated cardiovascular adverse effects.
Phase 2 RADIANCE Part A Results
Dr Skolnick presented data from the 96-week blinded extension portion of the phase 2, global, placebo-controlled, RADIANCE Part A clinical trial. The study enrolled patients with relapsing MS who had an Expanded Disability Status Scale score of 0 to 5.0, and who had ≥1 relapses in the previous 12 months or ≥1 relapses in the past 24 months plus ≥1 gadolinium-enhancing lesions on magnetic resonance imaging (MRI) in the 12 months before screening.
Data for 258 participants who were assigned to receive ozanimod (0.5 mg or 1 mg) or placebo once daily for 24 weeks. The study met its primary end point of reducing gadolinium-enhancing MRI lesions 12 to 24 weeks after treatment initiation. The mean cumulative number of gadolinium-enhancing lesions at 12 to 24 weeks was 11.1 with placebo versus 1.5 with ozanimod 0.5 mg (odds ratio [OR], 0.16; P <.0001) and 1.5 with ozanimod 1 mg (OR, 0.11; P <.0001). No serious cardiac events were reported in the study, said Dr Skolnick.
On May 22, 2017, Celgene announced in a press release that the phase 3 RADIANCE Part B clinical trial involving 1313 patients with relapsing MS also met its primary end point, which was the reduction in the annualized release rate compared with weekly interferon beta-1a (Avonex). Study result details are not yet available.
Two-Year Extension of RADIANCE Part A
Ozanimod showed continued efficacy on MRI and in clinical measures of MS activity for more than 2 years of the blinded extension period, reported Dr Skolnick. Patients who received ozanimod in the core study continued to receive ozanimod 0.5 mg (N = 85) or 1 mg (N = 81); those who initially received placebo in the core study switched to ozanimod 0.5 mg (N = 41) or 1 mg (N = 42) for the first time.
Approximately 90% of patients were free of gadolinium-enhancing lesions at the end of the extension study. The unadjusted annualized relapse rates were 0.38 with ozanimod 0.5 mg and 0.17 with ozanimod 1 mg; the 1-mg dose of ozanimod proved to be more effective than the 0.5-mg dose.
No Cardiac Issues
No new safety issues were reported in the blinded extension study, and no significant differences were seen between the 2 doses of ozanimod, said Dr Skolnick. With cardiac safety being a concern with fingolimod, the lack of cardiac issues with ozanimod is reassuring, he emphasized.
At least 1 adverse event (AE) was reported in the majority of patients, but no serious AE was considered drug-related. The most common AE was increased alanine aminotransferase levels, which occurred in 37% to 51% of patients who received ozanimod.
Other common AEs were nasopharyngitis, upper respiratory tract infection, urinary tract infection, and headache. No cases of macular edema, serious opportunistic infections, malignancy, or clinically significant pulmonary events were reported with ozanimod.
“The safety and tolerability results suggest a favorable benefit-to-risk profile for ozanimod that awaits confirmation in the ongoing phase 3 clinical trials, RADIANCE Part B and SUNBEAM,” said Dr Skolnick.
David E. Jones, MD, Assistant Professor of Neurology, James Q. Miller Multiple Sclerosis Clinic, University of Virginia Health System, Charlottesville, said that he welcomes the data on ozanimod, especially on its safety.
“It’s a more selective agent than fingolimod in that it only recognizes S1P subtypes 1 and 5. The assumption is that this will be associated with fewer cardiac side effects, and the data we heard today from RADIANCE suggest this is true. I think this is important,” said Dr Jones.
Initiating fingolimod can be “burdensome to providers and to patients,” because 6-hour monitoring is recommended to watch for “first dose phenomenon” (ie, a slowed heart rate), explained Dr Jones. For patients taking beta-blockers, calcium channel blockers, or other drugs that affect heart rate, 24-hour monitoring is recommended. Macular edema has also been observed with fingolimod therapy, but no such cases were reported in this study with ozanimod.
“Right now, it’s recommended that patients have an ophthalmic evaluation at baseline and 3 to 4 months after starting fingolimod, so this would be another aspect of convenience with this drug,” suggested Dr Jones.
Based on the combined results from the SUNBEAM and RADIANCE studies, a New Drug Application to the FDA for relapsing MS is expected by the end of 2017.