CITI Alert: $PFE Xeljanz CV Data Likely Increases Risks to Next Gen
JAK Approvals.
 Citi’s Take – Pfizer’s disclosure that higher dosage (10mg) of its JAK inhibitor
Xeljanz (tofacitinib) in patients with rheumatoid arthritis (RA) leads to increased
cardiovascular (CV) risk is reminiscent of FDA’s non-approval of LLY’s Olumiant
(baracitinib) for RA at the higher 4mg dose (see our report Baricitinib FDA Rejection
Painful but Broader Thesis Still Intact. Remain BUY dated 17 Apr 2017). We
forecast Xeljanz sales of $2.3bn in 2024 vs $3.6bn for consensus. While the CV
signal is at an unapproved dose and obviously Xeljanz specific, we anticipate that
the disclosure will likely raise the USFDA regulatory approval bar for next
generation JAK inhibitors (ABBV’s upadacitinib and Galapagos’ filgotinib). PFE has
indicated that it does not expect the disclosure to translate into any negative FDA
action on Xeljanz given unapproved dose and reassuring pooled safety data.
Despite PFE reassurance, we cannot eliminate the possibility that the FDA adds
warning to Xeljanz label despite reassuring pooled meta-analysis on approved
doses. MRK is our only Buy-rated name among the US majors. AstraZeneca,
Novartis, Sanofi, Bayer and Merck KGaA are our preferred names in EU.
 What’s new? Pfizer announced that the higher 10mg dose of its JAK inhibitor
Xeljanz (tofacitinib), in patients with rheumatoid arthritis, led to an increase in
pulmonary embolism and mortality in a post marketing study required by FDA. This
4400 patient study included patients who were 50 years or older with at least one
cardio risk factor and was designed to assess the risk of major cardiovascular
adverse events for tofacitinib versus TNF inhibitor (adalimumab/etanercept). The
independent Data Safety Monitoring Board (DSMB) determined that patients on the
10mg arm had higher mortality compared to the 5mg arm and patients on TNF
inhibitor. DSMB also noted that patients on tofacitinib 10mg arm experienced a
statistically and clinically important difference in the occurrence of pulmonary
embolism. Pfizer has not disclosed any additional data. We note that Galapagos
has long term data showing no incremental DVT risk.

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