Ozanimod on the PBS

Ozanimod was added to the Pharmaceutical Benefits Scheme (PBS) on 1 March 2021 for relapsing-remitting multiple sclerosis. Ozanimod is a sphingosine 1-phosphate receptor (S1PR) modulator that inhibits lymphocyte release from lymph nodes. This reduces lymphocyte migration into the central nervous system, which may prevent nerve inflammation and damage. Other medicines in this class that are listed on the PBS are fingolimod and siponimod.

There are five subtypes of the S1PR (S1PR_1-5), with ozanimod showing a high affinity for S1PR₁ and S1PR₅. Fingolimod is the least specific of the three agents, which is thought to be partly responsible for some of its adverse effects. A six-hour observation period is recommended for all patients after the first fingolimod dose. This is not routinely required on the initiation of ozanimod or siponimod.

There is a lack of head-to-head clinical trials comparing S1PR modulators. However, ozanimod’s efficacy was demonstrated in the SUNBEAM trial that used interferon beta-1a (30mcg weekly) as an active comparator. In this trial, the annualised relapse rate was 0.18 for patients taking ozanimod 920mcg daily, compared to 0.35 for interferon. The mean number of relapses in the year before treatment was 1.3 for all groups. The incidence of serious adverse events was low and similar across the treatment groups.

Ozanimod is initiated with a dose titration regimen to minimise bradycardia. Ozanimod has many potential drug interactions due to extensive metabolism by multiple enzyme systems, including cytochrome P450 and monoamine oxidase. Coadministration with rifampicin and monoamine oxidase inhibitors is not recommended.