Since July 15, 2020, a new drug for the treatment of relapsing multiple sclerosis, Zeposia® (active ingredient: Ozanimod), has been available in pharmacies. It should be noted that while the drug is new, it is based on an already known concept. Ozanimod belongs to the class of so-called Sphingosin-1-phosphate (S1P) receptor modulators and thus has the same target as Fingolimod (Gilenya®), which has been available for the treatment of relapsing MS since 2011, and as Siponimod (Mayzent®), which was recently approved for the treatment of active secondary progressive MS (SPMS).
But even though Ozanimod does not introduce a new concept into MS therapy, the drug is nevertheless welcome because it is the first S1P modulator to be approved as a first-line drug. As mentioned, Siponimod has only received approval for SPMS in Europe and Fingolimod should actually only be used in cases of highly active MS courses – according to professional information in patients who either still show disease activity despite an appropriate cycle of a disease-modifying therapy (e.g. with an interferon) or suffer from rapidly progressing severe relapsing multiple sclerosis, defined by more than two relapses in one year.
Despite the strict approval text, in Germany many patients with a “normally” active MS are of course also treated with Fingolimod because it is an effective and well-tolerated drug. With Ozanimod, however, the prescription of S1P modulators as first-line drugs becomes much easier, as it has a rather liberal approval text: It can “be used in adult patients with relapsing-remitting multiple sclerosis with active disease, defined by clinical and imaging findings”. This condition is ultimately met by most patients with relapsing MS, especially at the time of diagnosis. Accordingly, access to S1P modulators has become easier for newly diagnosed patients with the approval of Ozanimod, which is advantageous.
Another formal difference to Fingolimod is in the first intake. In contrast to Fingolimod, Ozanimod is slowly dosed up to the target dose of 0.92 mg. For this purpose, between the 1st and 4th day of treatment 1 x daily 0.23 mg are taken, from the 5th to 7th day of treatment 1 x daily 0.46 mg and from the 8th day on the target dose of 1x daily 0.92 mg is then treated. This dosing ensures a better cardiac tolerability of the substance, so that not every MS patient needs a cardiac monitoring at first administration. There should be an EKG before starting treatment. Only if pathological findings occur here (bradycardia, AV block) or if a heart attack or heart failure is found in the medical history, a 6-hour monitor monitoring is necessary at first administration. Ozanimod should not be given if there has been a previous heart attack in the last 6 months, unstable angina pectoris, decompensated heart failure or higher-grade rhythm disorders. Such pre-existing conditions are rather rare in MS patients, but the list shows the great similarity between Ozanimod and Fingolimod with regard to risks and side effects. We also speak here of so-called class effects. These class effects of the S1P modulators include the influence on the conduction system of the heart as well as the risk of liver function disorders, an influence on blood pressure, the occurrence of skin tumors, the risk of opportunistic infections and the rare macular edema. Also the possibility of a rebound after discontinuation of the substance and the warnings regarding pregnancy should be taken into account. We had to pay attention to these risks when using Fingolimod and should do so in the future also with Ozanimod.
On the other hand, it is also a good thing that we already know this class of substances very well – as a result, we can already quite accurately estimate the effects and side effects of the new drug. Particularly due to the good efficacy of the S1P modulators – even in direct comparison with interferon preparations – I believe that Zeposia® will achieve good acceptance among MS patients relatively quickly.
