No serious opportunistic infections reported

Relapsing multiple sclerosis (RMS) patients who had longer exposure to oral ozanimod HCl 1 mg (Zeposia) showed similar infection rates as patients who had ≤24 months’ exposure in controlled phase III trials, researchers reported.

The analysis included pooled data from two phase III trials of ozanimod (SUNBEAM and RADIANCE) as one population, which was compared with an overall RMS population that included participants in the open-label DAYBREAK extension study who completed any ozanimod RMS trial, including earlier phases. All participants were exposed to at least one dose of ozanimod HCl 1 mg.

The phase III population (n=882) had mean exposure of 18.1 months. Incidence of any infection was 35.1% (IR 300.5/1,000 person-years), with incidence of serious infection of 1.0%. The most common infections were nasopharyngitis (11.1%) and upper respiratory tract infection (5.9%). Most serious infections were typical bacterial infections that resolved without clinical sequelae. Opportunistic infections occurred in 1.8% (IR 12/1,000 person-years).

The overall RMS population (n=2,361) had a mean exposure of 32.0 months as of Jan. 2019. Overall infection incidence was 48.6% (IR 270.1/1,000 person-years) and incidence of serious infections was 1.7%, reported Hans-Peter Hartung, MD, of the University Hospital Dusseldorf in Germany, and coauthors. The incidence of opportunistic infections was 4.3% (IR 16.4/1,000 person-years).

The study was part the American Academy of Neurology (AAN) 2020 Science Highlights, which featured research that had been scheduled for presentation at the cancelled AAN annual meeting.

“In the overall RMS population that had longer mean exposure to ozanimod HCl 1 mg, overall rates of any infections and serious infections were similar to those with ≤24 months’ exposure in the phase III study population,” Hartung and colleagues wrote. “Non-serious herpes zoster infections were infrequent, but increased over time. No serious opportunistic infections have been reported with ozanimod.”

“The study is ongoing,” Hartung noted. “It has collected another year of exposure that will be communicated later in the year.”

Ozanimod reduces circulating lymphocytes by modulating sphingosine 1-phosphate (S1P) receptor subtype 1, a mechanism shared with fingolimod (Gilenya). This can reduce MS-associated inflammation, but potentially can increase susceptibility to infection, including progressive multifocal leukoencephalopathy (PML), which has motivated ongoing surveillance.

“All S1P receptor agonists expose MS patients to a higher risk of infection overall and opportunistic infection,” said Mark Freedman, MD, of the University of Ottawa in Canada, who was not involved with the study. “If we recall all the original studies with fingolimod that came out years ago, there were no study cases with PML. All the PML came out afterward.”

Ozanimod was approved by the FDA in March 2020 to treat relapsing forms of MS, including clinically isolated syndrome. FDA approval was based on the phase III SUNBEAM and RADIANCE trials that compared oral ozanimod HCl 1 mg/d and 0.5 mg/d with intramuscular interferon β-1a (Avonex) 30µg/week in adult RMS patients. Trial data showed adjusted annualized relapse rates at 2 years of 0.17 for ozanimod and 0.28 for interferon beta-1a. Imaging data for enhancing and new or enlarging T2 lesions also favored ozanimod, though no differences in 3- or 6-month confirmed disability rates were seen.

In the current analysis, the phase III study population had mean age of about 35 versus 36 in the overall RMS population; the proportion of females was 65.3% and 67.1%, respectively. Respective time since MS symptom onset was similar (6.9 versus 6.8 years) and prior exposure to any MS disease-modifying therapy was 28.6% in both groups.

The most common opportunistic infections in the phase III and the overall populations were oral herpes (0.7% versus 1.5%, respectively), herpes zoster (0.6% versus 1.4%, respectively), and herpes simplex (0.1% and 0.5%, respectively).

Lymphocyte studies found no association between absolute lymphocyte counts (ALC) of <0.2 × 109/L and serious or opportunistic infections. The percent of participants with minimal post-baseline ALC below that level was 3.3% in the phase III group and 6.9% in the overall RMS population. One serious infection (pyelonephritis) and one non-serious opportunistic infection (oral herpes) were seen, both in the overall population group.

Overall, no serious opportunistic infections were reported in either ozanimod group. While PML is rare, it may emerge with ozanimod “simply because it has the same mechanism of action as fingolimod,” Freedman noted. “The surveillance will be on and we’ll see whether the same thing transpires.”

  1. Relapsing multiple sclerosis (RMS) patients who had longer exposure to oral ozanimod HCl 1mg (Zeposia) showed similar infection rates as patients who had ≤24 months’ exposure in controlled phase III trials.

  2. Findings are based on analysis prepared for the American Academy of Neurology annual meeting and have not yet been peer-reviewed.

Paul Smyth, MD, Contributing Writer, BreakingMED™

The study was sponsored by Celgene, now part of Bristol Myers Squibb.

Hartung has received personal compensation from Bayer Healthcare, Biogen Idec, CSL Behring, GeNeuro, Genzyme, MedImmune, Merck Serono, Novartis, Opexa, Receptos, Roche, Sanofi, Teva, and Viela Bio.

Freedman reported relationships with Sanofi-Genzyme, Hoffman-La Roche, EMD Actelion, Alexion, Biogen Idec, Celgene, EMD Inc., Merck Serono, Novartis, Teva Canada Innovation, Atara Biotherapeutics, BayerHealthcare, Clene Nanomedicine, GRI Bio, Magenta Therapeutics, and MedDay.

Cat ID: 131

Topic ID: 82,131,730,131,36,192,167