Looking at recent Phase 3 trials results for Zeposia (ozanimod) reported by Bristol Myers Squibb, data and analytics company GlobalData says that the oral sphingosine1‐phosphate (S1P) could have an impact on the treatment paradigm for ulcerative colitis (UC) due to its oral route of administration—and, if priced competitively, the drug could be used before biologic therapy.
“Key opinion leaders (KOLs)interviewed by GlobalData have said that UC and Crohn’s disease (CD) patients would prefer an oral formulation over existing subcutaneously or intravenously delivered agents, as there is less concern surrounding immunogenicity and the route of administration is desirable,” wrote Patrick Aiyes, a senior healthcare analyst at GlobalData.
“Furthermore, the drug achieved US and EU approval for the treatment of multiple sclerosis (MS), has shown a promising efficacy profile in UC patients in early-stage clinical trials and achieved clinical remission of 16.4%, with a delta of 10.2% compared to placebo, in BMS’ Phase II TOUCHSTONE trial, which assessed the drug’s efficacy and safety. Should the full TRUE NORTH efficacy and safety dataset show positive results, Zeposia could potentially be the first oral drug to challenge Pfizer’s Xeljanz (tofacitinib) in UC.”
There have been concerns that S1P receptors can cause slowing of the heart rate in MS patients. However, in a study comparing the safety of Zeposia with Gilenya, two-year risks of adverse events leading to discontinuation such as bradycardia and abnormal enzymes were lower with Zeposia, GlobalData noted, adding that Zeposia also appears to have a better pharmacodynamic profile than Gilenya and has less long-lasting effects.
Added Aiyes: “Some KOLs interviewed by GlobalData stated that they would be happy to use Zeposia as a first-line treatment for moderate-to-severe UC and CD patients. However, should further safety signals emerge for ozanimod in UC, the drug may see similar safety restrictions applied - as noted for Xeljanz prescription in the US and EU. This would likely push ozanimod further down the UC treatment algorithm as a potential third or fourth-line treatment option”.
Although there is genuine excitement surrounding Zeposia in the inflammatory bowel disease community, Zeposia currently has a high annual cost of therapy in MS at almost $86,000 annually.
“If BMS is to maintain its high price point in the IBD markets, this could severely hamper its uptake as rival Xeljanz’s annual cost is around $60,000 annually and first-line IV-administered biologic Janssen’s Remicade (infliximab) is $35,000,” wrote Aiyes . “To help increase uptake, BMS could use separate branding in IBD, however, this is unlikely, as the company would want to protect pricing in the MS market.”
As far as the Bristo Myser Squibb take, the company reported that its True North trial of the drug met both primary endpoints, demonstrating highly statistically significant (p-value < 0.0001) results for induction of clinical remission at Week 10 and in maintenance at Week 52. The study also met key secondary endpoints of clinical response and endoscopic improvement in induction at Week 10 and in maintenance at Week 52.
The safety profile of Zeposia in the True North trial was consistent with that observed in previously reported trials. The company will complete a full evaluation of the True North data and work with investigators to present detailed results at a future medical meeting, as well as discuss these results with health authorities.
“Patients with ulcerative colitis can struggle to effectively manage this often unpredictable and potentially debilitating disease. The True North results are encouraging for patients living with moderate to severe ulcerative colitis as Zeposia demonstrated consistency across key clinical and endoscopic endpoints, suggesting Zeposia may address the need for new oral therapy options with a favorable benefit to risk profile in the treatment journey,” said Dr. Samit Hirawat, chief medical officer of Bristol Myers Squibb. “At Bristol Myers Squibb, we are committed to researching innovative treatment options that may elevate the standard of care for people living with ulcerative colitis, with a focus on finding solutions that have the potential to transform outcomes for the inflammatory bowel disease community.”