Pfizer Reports XELJANZ (Tofacitinib) Did Not Meet Non-Inferiority Criteria vs. TNF Inhibitors in Post-Marketing RA Safety Study

January 27, 2021/BioValleyBIOON/--Pfizer(Pfizer) recently announced the completion of a recent evaluation assessing the oral JAK inhibitor Xeljanz (tofacitinib, 托法替尼) for the treatment of rheumatoidRheumatoid ArthritisCo-primary endpoint results from the post-approval required safety study ORAL Surveillance (A3921133, NCT02092467) in rheumatoid arthritis (RA). The primary objective of this study was to evaluate the safety of two doses of Xeljanz (5 mg twice daily and 10 mg twice daily) versus a tumor necrosis factor inhibitor (TNFi) in RA patients aged ≥50 years with at least one additional cardiovascular (CV) risk factor.

The co-primary endpoints of this study were major adverse cardiovascular events (MACE) and malignantTumor(excluding non-MelanomaNon-inferiority of Xeljanz compared to TNFi in terms of skin cancer [NMSC].The results showed that for these co-primary endpoints, the prespecified non-inferiority criteria were not met in the initial comparison of pooled Xeljanz doses versus TNFi.According to the prespecified secondary comparisons, there was no difference in the primary endpoint between the two Xeljanz treatment groups.

This study included 4,362 subjects who received the study treatment. The primary analysis included 135 patients with MACE and 164 patients with malignancies (excluding NMSC). For Xeljanz, the most commonly reported MACE wasMyocardial Infarction, the most common malignant tumor (excluding NMSC) is lung cancer. In those with MACE and malignantTumorAmong subjects with a higher prevalence of known risk factors (e.g., advanced age, smoking), the incidence of events was higher in all treatment groups.

Full study results have not yet been obtained, apart from the co-primary endpoints (including but not limited to secondary endpoints such as pulmonary embolism and mortality, as well as efficacy data). Pfizer is working with the U.S. Food and Drug Administration (FDA) and other regulatory authorities, to be reviewed upon the availability of complete results and analyses.

Pfizer Inflammation andImmunologyDr. Tamas Koncz, Chief Medical Officer, stated: “It is essential to provide information on the safe and effective use of our medicines. We believe that conducting extensive additional analyses of these study data and communicating them as soon as possible will further clarify the benefits and risks of Xeljanz, thereby supporting medical decision-making and patient care.”

The active pharmaceutical ingredient of Xeljanz is tofacitinib, an oral JAK inhibitor that selectively inhibits JAK kinases and blocks the JAK/STAT pathway. This signaling pathway is a cytokine-stimulated signal transduction cascade involved in many important biological processes, including cell proliferation, differentiation, apoptosis, and immune regulation.

Xeljanz was approved in the United States in 2012 as the first marketed JAK inhibitor, administered orally twice daily. Currently, Xeljanz has been approved for four indications: (1) treatment of moderate to severe active rheumatoidRheumatoid Arthritis(1) Adult patients with rheumatoid arthritis (RA); (2) Adult patients with active psoriatic arthritis (PsA); (3) Adult patients with moderate to severe ulcerative colitis (UC); (4) Pediatric and adolescent patients aged ≥2 years with polyarticular course juvenile idiopathic arthritis (pcJIA).

It is worth noting that Xeljanz is the first and only JAK inhibitor approved in the United States for the treatment of pcJIA. This approval covers two formulations of Xeljanz: tablets and an oral solution, with dosing based on body weight.

In the Chinese market, Xeljanz was approved for launch in March 2017 for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to or intolerance to methotrexate (MTX). Xeljanz can be used in combination with MTX or other non-biologic disease-modifying antirheumatic drugs (DMARDs). The approved recommended dosage is 5 mg taken orally twice daily, with or without food. This approval makes Xeljanz the first...Rheumatoid Arthritis(RA)'s first JAK inhibitor. (Bioon.com)

Original Source: Pfizer Shares Co-Primary Endpoint Results from Post-Marketing Required Safety Study of XELJANZ® (tofacitinib) in Subjects with Rheumatoid Arthritis (RA)