On March 8th, 2018 the FDA Gastrointestinal Drugs Advisory Committee (GDAC) discussed the supplemental new drug application (sNDA) 203214 supplement 18, for XELJANZ (tofacitinib) 5 mg and 10 mg tablets, submitted by Pfizer Inc., for the treatment of adults with moderate to severely active ulcerative colitis (UC) who have had inadequate response, loss of response, or intolerance to conventional therapies or Tumor necrosis factor (TNF) inhibitor therapy.

THE SPONSOR PROPOSED THE FOLLOWING DOSING REGIMEN:

• 10 mg BID for 8 weeks and followed by 5 mg BID as maintenance therapy.
• 10 mg BID induction therapy continued for an additional 8 weeks (16 weeks in total) for patients without adequate therapeutic response at 8 weeks.
• a higher maintenance dose treatment option of 10 mg BID continuous dosing, for patients with history of prior failure to TNF blocker.

Tofacitinib is a small molecule inhibitor of Janus associated kinases (JAK). Tofacitinib is currently approved for adults with severely active rheumatoid arthritis (RA) (November 2012) at a dose of 5 mg BID and for adults with active psoriatic arthritis (February 2017).

IN THIS MEETING, THERE WERE 4 DISCUSSION QUESTIONS AND THE COMMITTEE VOTED ON THREE TOPICS:

1) the adequacy of efficacy data to support the use of the 10 mg BID dosing for extended induction therapy for a total of 16 weeks in patients who have not achieved “adequate therapeutic benefit” by Week 8;

2) the adequacy of the efficacy data to support the use of the 10 mg BID dosing as continuous maintenance treatment and;

3) whether additional post-marketing evaluations of efficacy and safety were warranted.

THE COMMITTEE VOTED UNANIMOUSLY (15 YES, 0 NO) IN FAVOR OF EXTENDING THE USE OF 10 MG TOFACITINIB TWICE DAILY FROM 8 TO 16 WEEKS OF INDUCTION IN ADULTS WITHOUT ADEQUATE RESPONSES AT WEEK 8.

Likewise, the committee were united in support of the 10 mg twice-daily dose as maintenance therapy for patients with inadequate response, loss of response or intolerance to anti-TNF therapy.

Regarding the post-marketing efficacy study, with a split vote (7 Yes, 8 No), the committee did not recommend that the sponsor conduct a trial comparing a 10 mg BID continuous dosing regimen vs a regimen of 10 mg induction and 5mg BID as maintenance.

ALTHOUGH NOT OBLIGATED TO TAKE THE ADVICE OF THE ADVISORY COMMITTEE, THE FDA NORMALLY DOES SO.

A decision on tofacitinib for UC is expected by June of 2018. If approved, tofacitinib would present the first orally administered agent approved for patients with moderate to severe UC.

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