Although five oral drugs are being developed in the late stage ulcerative colitis (UC) pipeline, a window of opportunity still remains
for pharmaceutical companies in this space, says GlobalData, a leading data and analytics company.
Novel oral therapies in the UC market have been identified as a significant unmet need. Currently, only one oral therapy has been
approved for UC in the US which is 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, immunogenicity, and would also help patients to stop and restart
therapy without risks.
Patrick Aiyes, MEng, Pharma Analyst at GlobalData, comments: “Xeljanz seems likely to receive approval in Japan and Europe, and we
believe that there will be four more oral therapies approved for UC in the next five years. This has raised 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 within UC in the forecast period from 2016–2026, producing sales of $606.8m combined across the
seven major markets (7MM*). 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 hematalogic side effects. KOLs suggest that although JAK
inhibitors have high efficacy, there are slight concerns over their safety profiles. However upadacitinib and filgotinib have slightly
better safety profiles, nevertheless KOLs have indicated 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 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 favorable efficacy in its Phase II trials. KOLs suggested
that carotegrast will provide effective competition with 5-aminosalicylic acid (5-ASA) therapy; however, the drug is only being
developed in Japan.
Aiyes adds: “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 mechanisms of
action for severe-to-fulminant patients, marking another opportunity for pharmaceutical companies.”
* 7MM: US, France, Germany, Italy, Spain, UK, and Japan