Pfizer’s New Oral Investigational JAK Inhibitor Shined in Two Pivotal Phase 3 Ulcerative Colitis Trials


Recently, during the 11th Congress of European Crohn’s and Colitis Organisation (ECCO) Pfizer revealed the results of its two pivotal Phase III trials from the Oral Clinical Trials for tofAcitinib in ulceratiVE colitis (OCTAVE). It was designed to evaluate the safety and efficacy of tofacitinib 10 mg oral dose twice a day among patients suffering from moderate to severe ulcerative colitis.

Tofacitinib interferes with JAK-STAT kinase signalling pathway by inhibiting enzymes Janus kinases (JAK 1Tofacitinib2DACS.svg and JAK 3) that transmits extracellular information to the cell and in turn regulate the transcription process. Inhibition of JAKs by tofacitinib prevents inflammation and tissue destruction which is found to be associated with many inflammatory diseases. It was approved for treatment of rheumatoid arthritis in 2012. It is marketed under the name Xeljanz and Jakvinus and was  discovered and developed by Pfizer and the National Institutes of Health.

Ulcerative colitis is a kind of chronic inflammatory bowel disease that affects large intestine of the gastrointestinal tract. In this disease the intestinal lining becomes inflamed with tiny open sores and ulcers that produce pus and mucus. Generally elderly people have more chances to acquire this disease.

Because of the intolerance and negative responses to conventional therapies, to date there are no treatment available for the permanent cure of ulcerative colitis. In OCTAVE trials, tofacitinib were noticed reducing ulcer symptoms in moderate to severe conditions; by remission of the disease among patients who have failed previous treatment with anti-TNFs and its effectiveness was more as compared to placebo treated groups. Also, patients receiving tofacitinib showed a higher rate of mucosal healing compared to placebo during the 8th week of study.

Tofacitinib safety profile has been found to be similar to its earlier investigational clinical profile. From that it has been observed that in addition to its pharmacological actions it has some adverse effect (AE) or severe adverse effect (SAE). In both OCTAVE studies 1 and 2, it has been observed that the occurrence of AE and SAE in tofacitinib treated group was less as compared to placebo treated groups. Also, the most common AE for discontinuation of study in both trials was the ulcerative colitis flare.

Featured image credit: Ulcerative Colitis © vitanovski (Stock Photo ID: 103176314)

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