The market for ulcerative colitis (UC) is filled with various treatment options, and the pipeline is relatively strong. The variety of drug classes currently available for the treatment of UC across the eight major markets (8MM: the US, France, Germany, Italy, Spain, the UK, Japan, and Canada) includes 5-amino salicylates (ASAs), steroids, immunomodulators, anti-tumour necrosis factor (anti-TNF) therapies, anti-interleukin therapies, anti-integrin therapies, Janus kinase (JAK) inhibitors, and sphingosine 1-phosphate (S1P) receptor modulators. A notable agent in the late-stage UC pipeline is Pfizer’s etrasimod, a once-daily oral S1P receptor modulator.

There is currently a spotlight on etrasimod after Pfizer presented an updated safety analysis of the cumulative safety profile observed during etrasimod’s clinical development programme, including OASIS (NCT02447302), ELEVATE UC 52 (NCT03945188), ELEVATE UC 12 (NCT03996369), and the ongoing ELEVATE UC OLE (NCT03950232). This data was presented at the Digestive Disease Week (DDW) 2023 conference, and it showcased 2.5 years of pooled etrasimod safety data. Etrasimod is anticipated to be the second S1P modulator and the fifth small molecule therapy to be approved in moderate-to-severe UC. The drug is anticipated to be approved behind small molecule therapies such as the pan-Janus kinase (JAK) inhibitor Xeljanz (tofacitinib), Bristol Myer’s Squibb’s (BMS) competitor S1P modulator Zeposia (ozanimod) approved in the US and EU in 2021, and JAK-1 selective inhibitors including Gilead/Galapagos’s Jyseleca (filgotinib) approved in the EU in 2021, and AbbVie’s Rinvoq (upadacitinib) approved in the US and EU in 2022. According to GlobalData’s report Ulcerative Colitis: Eight-Market Drug Forecast and Market Analysis, the UC market is forecasted to reach 2031 sales of approximately $9.6bn across the 8MM, with 8% of this sales value anticipated to come from the S1P class, translating to a value of $797.4m; over half of those sales are anticipated to come from etrasimod.

The safety analysis highlighted particular adverse events of interest, especially those believed to be associated with S1P modulators. These included cardiovascular events, macular oedema, severe opportunistic infections, herpes zoster infections, and malignancies; a few of these infections were reported with a similar incidence between treatment arms and placebo. BMS also focused on the aforementioned adverse events during the European Crohn’s and Colitis Organization (ECCO) 2023 conference, with the company presenting efficacy and safety data associated with three years of continuous Zeposia treatment. This presentation highlighted the long track record of the drug in UC, which will likely improve physician confidence in this asset. The company also presented mucosal healing data at DDW 2023, which further strengthened BMS’s position in the UC therapy space as the competition for second-line treatment is expected to intensify. However, KOLs interviewed by GlobalData mentioned that they are not familiar with Zeposia and that they have little to no experience with the agent. Furthermore, some discussed that although S1P modulators provide another option for patients, there is still a lot to learn about the MOA. It is expected that Pfizer will continue to collect long-term safety data from the ongoing open-label extension Phase III ELEVATE UC OLE study to generate supporting data to leverage at future conferences to bolster etrasimod’s perception as a safe oral therapy in UC. GlobalData anticipates etrasimod will enter the US market in 2024 but given its late entrance into a crowded UC market, etrasimod will likely need to demonstrate both efficacy and safety benefits over its direct competitor, Zeposia.