The Safety of Other S1P Receptor Modulators in Multiple Sclerosis

Krzysztof Selmaj, MD, PhD: We have data on the long-term safety for fingolimod and ponesimod. And specifically impressive in terms of the length is the data from fingolimod because it came from the long-term study, which altogether lasted from the initiation to the completion of more than 18 years, and it considered more than 4000 patients. So this is a large population. And this data, the safety data from this cohort, showed that the rate of viral infection was about 10%. Hypertension occurred in 13% of patients. The lymphopenia in slightly above 10%. Basal cell carcinoma in 0.9% of patients. And [the] discontinuation rate, as I mentioned I think earlier, was 5.5%. So although the safety for these non-selective S1P [sphingosine 1-phosphate] receptor modulators showed somehow slightly higher parameters comparing to the ozanimod, which I presented just before, but still there was a relatively accepted profile of safety for fingolimod. For the ponesimod, we have also observation with data from long-term observation. It lasted about 8 years. The cohort of patients was much smaller [compared] to fingolimod, also much smaller [compared] to ozanimod, because it’s also of 435 patients. And the major difference in the safety profile between the ponesimod and of the other S1P receptor modulators was the effect of the liver enzyme. And because the frequency of increase of liver enzymes was higher [compared] to other studies, and for example, for ALT, the increase of X was at the level of 10%. And macular edema was also with higher frequency, 2.8%. So there are some differences between these drugs in terms of safety. And it might depend on the different kinetics, different site of interaction with S1P receptors. And in particular, in terms of ponesimod, it targets on the one receptor type 1, so it also might somehow contribute to these differences.