Following Bristol Myers Squibb’s positive topline results from its pivotal Phase III TRUE NORTH trial, it is possible that oral sphingosine1‐phosphate (S1P) Zeposia could have an impact on the treatment paradigm for ulcerative colitis (UC) due to its oral route of administration. If priced competitively, the drug could be used before biologic therapy, says GlobalData, a leading data and analytics company.

Patrick Aiyes, MEng, Senior Healthcare Analyst at GlobalData comments: “Key opinion leaders 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.

“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. Furthermore, Zeposia also appears to have a better pharmacodynamic profile than Gilenya and has less long-lasting effects.

Aiyes continues: “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 (IBD) community, Zeposia currently has a high annual cost of therapy in MS at almost $86,000 annually.

Aiyes concludes: “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. 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.

“An alternative pricing strategy could be developed if dosage in IBD is different from BMS. Currently, Zeposia is being investigated at a dose of 0.46mg in both CD and UC, as well as the higher 0.92mg dose that is used for MS maintenance therapy.”

*  Clinical remission defined as Mayo score ≤ 2, no subscore >1