Pfizer’s Xeljanz impresses in ulcerative colitis in latest attempt to expand portfolio

Phase 3 data for Pfizer’s JAK inhibitor Xeljanz (tofacitinib) in ulcerative colitis has met both primary and secondary safety and efficacy endpoints.

The data were presented at the European Crohn’s and Colitis Organisation (ECCO) Congress and comes from the first two phase 3 Oral Clinical Trials for tofacitinib in Ulcerative Colitis (OCTAVE) programme.

The results could help Pfizer in its attempts to expand use of Xeljanz, which has so far failed to live up to blockbuster expectations.

The drug’s oral formulation gives it an advantage over the established anti-TNF drugs such as AbbVie’s Humira, but doubts about its safety and efficacy have held it back. First approved in 2012 for rheumatoid arthritis as a second line treatment after anti-TNFs, the drug achieved strong sales growth in 2015. Its revenues rose to $523 million, but this represents a small fraction of a multi-billion dollar market.

Safety concerns about the drug have held it back in particular, the drug raising the body’s susceptibility to infections such as tuberculosis and other opportunistic microbial infections. In October, the FDA rejected Pfizer’s application for a licence in moderate to severe cases of plaque psoriasis, although the company has pledged to address the concerns raised.

The OCTAVE 1 and 2 inductions investigated the safety and efficacy of oral Xeljanz 10mg twice daily compared to placebo in adults with moderately to severely active ulcerative colitis.

In these trials, the drug seemed to perform similarly to placebo in terms of its safety profile, though incidence of adverse events (AEs) and serious adverse events (SAEs) were high. In OCTAVE Induction 1 and 2, treatment-emergent AEs were reported in 56.5% (259) and 54.1% (232) of patients taking tofacitinib 10 mg BID, as compared to 59.8% (73) and 52.7% (59) of patients in the placebo group, respectively. In both OCTAVE Induction studies, the most common AE leading to discontinuation across all treatment groups was UC flare.

In terms of its efficacy, Xeljanz achieved a greater percentage of remission in participants (the primary endpoint) as well as a greater percentage of mucosal healing (the secondary endpoint) in both trial arms.

Geert D’Haens, MD, PhD, study investigator and Professor of Gastroenterology at The Academic Medical Center (AMC), University of Amsterdam, said he was encouraged by the results, which showed tofacitinib reduced symptoms of moderate to severe ulcerative colitis and induced remission of the disease.

The trial looked at patients previously treated with tumour necrosis factor inhibitors (TNFis) as well as those who had not, opening up the possibility for Pfizer to file the drug as a first line treatment in UC.

In OCTAVE 1, 18.5% (n=88) of participants taking Xeljanz experienced remission versus 8.2% (n=10) in the placebo group – a proportion mirrored in OCTAVE 2, where 16.6% (n=71) of the Xeljanz group experienced remission, in contrast to 3.6% (n=4) of the placebo group.

The pattern remained the same in each trials’ secondary endpoints, with 31.3% of the Xeljanz group compared to 15.6% of the placebo group in OCTAVE 1, and 28.4% versus 11.6% in OCTAVE 2, achieving mucosal healing after 8 weeks.

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