Safety and efficacy consistent at 4 years

Treatment with the sphingosine-1-phosphate (S1P) receptor 1 and 5 modulator ozanimod maintained its effectiveness over at least 4 years, and researchers reported that no opportunistic infections or other unexpected adverse events popped up during that period among patients diagnosed with relapsing-remitting multiple sclerosis.

“In DAYBREAK, ozanimod was associated with low annualized relapse rates and low new or enlarging T2 and gadolinium-enhancing lesion counts over time,” said Krzysztof Selmaj, MD, professor of neurology at the University of Warmia and Mazury, Olsztyn, Poland. “Most patients were relapse free and did not experience disability progression.”

The primary goal of the extension trial was to evaluate safety in the overall population, he said in his presentation at the 2020 virtual joint meeting of the American Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS).

To that point, Dr. Selmaj said, “Ozanimod was generally well tolerated and no new safety concerns emerged with long-term use.”

In the ongoing DAYBREAK extension trial, he and colleagues enrolled participants with relapsing multiple sclerosis who participated in 4 Phase 1, Phase 2, or Phase 3 ozanimod clinical trials. In the trials they received oral ozanimod 0.92 mg/d. The trial included 2,494 participants and were exposed to ozanimod for a mean of 49.5 months, which including time in the parent trials and in DAYBREAK, Dr. Selmaj said.

He noted that the annualized relapse rate was low in the parent trials – in the 0.110% to 0.119% range — and continued to be low in the DAYBREAK population where the rate was 0.112%, he said.

He said the same was true for T2 lesions and gadolinium-enhancing lesions, with 1.8 new/enlarging lesions per scan observed with T2 lesions, and a rate of 0.3 new gadolinium-enhancing lesions per scan. The rates were similar among patients who had been on interferon therapy in the comparative part of the trial before going on ozanimod; if they had received low dose ozanimod before going on the higher dose being used in DAYBREAK, and among patients who had continuously been on the high dose of ozanimod, Dr. Selmaj reported.

In reviewing the safety profile, he reported that any treatment-emergent adverse events were reported in 81.8% of the DAYBREAK cohort. Severe treatment-emergent adverse events were reported by 6.1% of the patients in the study. Serious treatment-emergent adverse events occurred among 9.5% of the patients. The researchers reported that 2.2% of the patients in the study permanently discontinued treatment due to treatment-emergent events.

In commenting on the study, Asaff Harel, MD, assistant professor of neurology at Lenox Hill Hospital/Hofstra School of Medicine/Northwell Health, New York City, says. “This follow-up represents a work in progress. At every medical conference there are reports of long-term safety and efficacy of all kinds of medications. People do want to know if these treatments maintain their effectiveness and long-term safety. While this study involves 2,500 people over a follow-up of 4 years, it probably still does not tell us enough about long-term side effects,” Dr. Harel said. “It is nice to have this information, but we have not had enough time with ozanimod to see anything new. That being said, I think we are pretty comfortable with the safety profile of this class of drugs. We know what to expect with this drug.”

Dr. Harel noted that the presentation did not discuss at length the types of serious adverse events. “They reported a 9.5% incidence of serious adverse events,” Dr. Harel said. “That might be concerning. I think we have to know what they mean by serious events and what those events were. There were no opportunistic infections, but was there sepsis or other issues?

“However, since just 2.2% of the patients had to discontinue therapy, it may be that the serious adverse events were not enough to lead to stopping of the drug,” he suggested. “We know that S1P modulators are associated with infections, so that is something to be watchful about.”

Dr. Harel said that continued surveillance for adverse events – especially rare opportunistic infections – is warranted. “We do expect to see these infections emerge with these agents,” he said. “It is something that has to be monitored over time.”

  1. In an ongoing study, treatment with ozanimod did not have unexpected treatment-emergent adverse event.
  2. The study found consistent low annualized relapse rates among these patients with relapsing multiple sclerosis.

Edward Susman, Contributing Writer, BreakingMED™

The study was funded by Bristol Myers Squibbb (Celgene).

Dr. Selmaj disclosed relationships with Biogen, Celgene, Genzyme, Merck, Novartis, Ono Pharmaceuticals, Roche, Synthom, and Teva.

Dr. Harel disclosed relationships with Biogen, Banner Life Sciences, and Alexion.


Cat ID: 130

Topic ID: 82,130,730,130,36,709,192,925,708