According to GlobalData’s latest analysis report about the ulcerative colitis (UC) market, novel oral therapies has been identified as a significant unmet need.

Currently, only one oral therapy has been approved for UC in the US: Pfizer’s first-in-class Janus kinase (JAK) inhibitor, Xeljanz (Tofacitinib). Key opinion leaders (KOLs) interviewed by GlobalData have been vocal about the need for novel oral therapies in the UC space, as they would help to reduce the risks of the development of antibodies and immunogenicity, and would also help patients to stop and restart therapy without risks. Xeljanz seems likely to receive approval in Japan and Europe, and GlobalData believes that there will be four more oral therapies approved for UC in the next five years.  This has raised the questions about whether or not the need for novel oral therapies will be fulfilled by these pipeline agents, and whether or not opportunity for new entrants remains in the UC space.

GlobalData anticipates the JAK inhibitors, including Pfizer’s Xeljanz, Gilead/Galapagos’ filgotinib, and Abbvie’s upadacitinib, to be the third highest grossing drug class in the forecast period from 2016–2026, producing sales of $606.8m combined across the seven major markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan). Xeljanz has a slightly different mechanism of action (MOA) to both filgotinib and upadacitinib, which have highly selective JAK1 inhibition; Xeljanz’s JAK 2 inhibition could cause some hematologic side effects. KOLs interviewed by GlobalData suggest that although JAK inhibitors have high efficacy, there are slight concerns over their safety profiles. Although upadacitinib and filgotinib have slightly better safety profiles, KOL’s have indicated that this will not be enough to differentiate them from Xeljanz.

Celgene ’s ozanimod, which is a first-in-class sphingosine-1-phosphate receptor 1 (S1P1) for moderate to severe UC, met both of its primary efficacy endpoints in its Phase II TOUCHSTONE trial and boasted a very strong safety profile. However, KOLs interviewed by GlobalData have noted that it has a slow onset of action, which is not ideal for an oral drug. EA Pharma ’s carotegrast, an alpha 4 integrin antagonist that is being evaluated for patients who suffer from mild to moderate UC, demonstrated favourable efficacy in its Phase II trials. KOLs interviewed by GlobalData suggested that carotegrast will provide effective competition with 5-aminosalicylic acid (5-ASA) therapy; however, the drug is only being developed in Japan.

Although five oral drugs are being developed in the late stage UC pipeline, a window of opportunity still remains in this space. UC is a lifelong, chronic disease that requires long-term medical management. Oral therapies are preferred over other routes of administration due to ease of administration. However, all the therapies under development have unique weaknesses with safety and speed of action. Furthermore, they are all available for moderate-to-severe and mild-to-moderate UC patients, but there are no new oral MOAs for severe-to-fulminant patients, marking another opportunity for pharmaceutical companies.