Opinion
Video
Long-term Data With Ozanimod in Relapsing-Remitting Multiple Sclerosis
Author(s):
Bruce Cree, MD, PhD, MAS, reviews the results of the long-term efficacy and safety study of ozanimod, DAYBREAK, in relapsing-remitting multiple sclerosis (RRMS) published last year. Dr Cree also discusses two other safety studies presented at the 2023 European Academy of Neurology (EAN) congress.
Transcript
Bruce Cree, MD, PhD, MAS: In terms of ozanimod, there was a long-term follow-up study for ozanimod. There were several clinical trials that were performed with ozanimod, there is a phase 2 clinical trial, and then 2 phase 3 clinical trials. These all lead into a long-term follow-up study called DAYBREAK [NCT02576717]. The goal of the DAYBREAK study was to acquire both safety and efficacy data at the output ozanimod in terms of its long-term usage. Those individuals who went into the study—there were nearly 2,500 participants, and they were followed over about a 4-year period of time, some a little longer, some a little bit shorter. Overall, in terms of the efficacy of ozanimod, we saw quite low annualized relapse rates on the order of about 0.1, which weights for about 1 relapse every 10 years. The large majority of participants had no progression, in terms of disability workstream, and 70% were progression free. The safety data also was very consistent with what was observed in the randomized control trial portion. We didn’t really see new safety signals that came out of this long-term study. There was one case of PML [progressive multifocal leukoencephalopathy] that was reported, and the details of that case have been presented.
Bruce Cree, MD, PhD, MAS: At the recent EAN [European Academy of Neurology] meeting, this summer of 2023, there were updates on the safety profile for ozanimod from the DAYBREAK extension study. Now, the DAYBREAK study involves patients who had participated in the phase 2 and phase 3 clinical trial programs. These patients went into a longer-term follow-up where they were observed in the DAYBREAK study. The goals of the study were to assess safety and efficacy over time. There were a few presentations at the EAN that addressed safety and efficacy, or primarily safety. The first was a study looking at hepatic abnormalities in a clinical trial; this is an important consideration, especially in light of recent observations about drug-induced liver injury from some of the therapies which are in development currently, the Bruton’s tyrosine kinase inhibitors. Here, we had an opportunity to look at the hepatic functions and other hepatic events associated with ozanimod over the long term. In general, hepatic laboratory abnormalities, although they occurred with some degree of frequency for a mild elevation in transaminases, in terms of more serious elevations, [were] either 3- or 5-fold over the upper limit of normal use for relatively infrequent events. In terms of other hepatic events, there were a number of hepatic events that led to frequent discontinuation out of nearly 2,500 participants. There was 1 case of acute hepatitis and 1 case of sphincter of Oddi dysfunction that led to discontinuation. There were a total of 9 events that were related to liver functions that were laboratory events that led to treatment discontinuation. This is actually a very low rate for a part of biliary disorders in general; this was a rate of about 0.8. For the laboratory abnormalities, that rate is about 0.4%. So very infrequent, frequent discontinuations. There were no cases of drug-induced liver injury. I think this is an important point with respect to this particular product. Hepatic abnormalities may occur, they do tend to be transient, and self-limited, [and] they tend to resolve on their own even without treatment discontinuation. Therefore, tight monitoring of liver functions with this particular product probably is not necessary. We’ve got now about up to 6 years ozanimod exposure, elevation in transaminases. Overall, it was infrequent, occurring in less than 4% of the patient population. They rarely resulted in frequent discontinuation. The second study that was reported at the EAN looked at overall rates of abnormal treatment emergent adverse events, infections, opportunistic infections, hepatic disorders, cardiac disorders, and so on. Generally speaking for all of these events, they tended to occur more frequently during the phase 3 program. Then over time, as patients went into the open label extension study, these events decreased in frequency, which is interesting. It’s almost as if you’re going to have an adverse event, you’re more likely to have that adverse event sometime shortly after initiating treatment, but then, you’re probably going to become less likely to have the events over time. I think that’s an interesting observation. There was one important exception to this, which had to do with serious infections, which of course went up during the COVID-19 pandemic. We saw an uptick in serious infections over time largely attributable to COVID-19-related infections. Overall, these adverse events were relatively uncommon during the course of the studies. Of course, the study in particular adverse events and particular interest such as macular edema, which occurred quite infrequently; the incident rate for that was only about 0.3. So, very low incident rate for macular edema. In conclusion, this particular study showed low rates overall of adverse events that were of special interest over time. These events were consistent with the overall safety profile of this product, ozanimod.
Transcript edited for clarity.
