FDA approves sNDA to include radiographic data updating label of Pfizer XELJANZ for treatment of RA

Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) to update the current label of XELJANZ^® (tofacitinib citrate) 5 mg tablets to include radiographic data from two Phase 3 studies, ORAL Scan (A3921044) and ORAL Start (A3921069). "XELJANZ is the first oral JAK inhibitor for moderately to severely active rheumatoid arthritis. The reduction of radiographic progression seen in ORAL Scan and ORAL Start represents a clinically meaningful outcome for patients," said Dr. Steven Romano, Global Medicines Development Lead for the Pfizer Global Innovative Pharmaceutical business.

XELJANZ is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate (MTX). XELJANZ may be used as a single agent or in combination with MTX or other non-biologic disease-modifying antirheumatic drugs (DMARDs). Use of XELJANZ in combination with biologic DMARDs or potent immunosuppressants, such as azathioprine and cyclosporine is not recommended. The recommended dose is 5 mg twice-daily (BID).

The U.S. Prescribing Information contains a boxed warning for serious infections and malignancies. Patients treated with XELJANZ are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as MTX or corticosteroids. Lymphoma and other malignancies have been observed in patients treated with XELJANZ.

The updated U.S. label now includes the radiographic response data from ORAL Scan (Study IV) at 6 months and ORAL Start (Study VI) at 6 and 12 months (see detailed study descriptions below the table). These studies evaluated the effect of XELJANZ on the progression of structural joint damage as measured by mean change from baseline in van der Heijde modified Total Sharp Score (mTSS) and its components, erosion score and joint space narrowing (JSN) score. The proportion of patients with no radiographic progression (mTSS change from baseline less than or equal to 0) was also assessed.

^aSD = Standard Deviation
^bDifference between least squares means XELJANZ minus placebo or MTX (95% CI = 95% confidence interval)
^CMonth 6 and Month 12 data are mean change from baseline.

In the placebo plus MTX group in ORAL Scan (Study IV), 74 percent of patients experienced no radiographic progression at Month 6 compared to 84 percent of patients treated with XELJANZ 5 mg BID plus MTX.

In the MTX group of ORAL Start (Study VI), 55 percent of patients experienced no radiographic progression at Month 6 compared to 73 percent of patients treated with XELJANZ 5 mg BID.

It is important to note that the U.S. label specifies that use of live vaccines should be avoided concurrently with XELJANZ. Update immunizations in agreement with current immunization guidelines prior to initiating XELJANZ therapy.

The ORAL Start study showed that XELJANZ 5 mg BID, as a single agent, was statistically significantly superior to MTX, providing a greater inhibition of progression of structural joint damage, as measured by mean change from baseline in mTSS at Month 6 (primary endpoint), and sustained at 12 months (refer to table above). The study was conducted in MTX-naïve patients with moderately to severely active RA who were randomized to receive XELJANZ 5 or 10 mg BID or to MTX dose-titrated over 8 weeks to 20 mg weekly. XELJANZ is not indicated for use in MTX-naïve patients. The safety experience of the patients in ORAL Start was consistent with the results of the five Phase 3 pivotal trials.

The risks and benefits of treatment should be considered prior to initiating XELJANZ in patients with chronic or recurrent infection; who have been exposed to tuberculosis; with a history of a serious or an opportunistic infection; who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection.

The ORAL Scan study demonstrated that XELJANZ 10 mg BID provided statistically significantly greater reduction of progression of structural joint damage as measured by mean change from baseline in mTSS compared to placebo at 6 months (primary endpoint - refer to table above). Results for the 5 mg BID dose exhibited similar effects on mean progression of structural damage but were not statistically significant (refer to table above). The ORAL Scan study was conducted in patients with moderately to severely active RA who had an inadequate response to MTX. Patients were randomized to receive XELJANZ 5 or 10 mg BID or placebo, and all treatments were added to background MTX. The controlled period for the study ended at 6 months. The 10 mg BID dose is not approved.

It is important to note that the U.S. label says viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), was observed in clinical studies with XELJANZ. XELJANZ should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis).