Janus Kinase Inhibitor Fares Well in Phase 3 Trial

Tasocitinib (CP-690,550) has been found to reduce the signs and symptoms of rheumatoid arthritis considerably, as well as significantly improving physical function according to a Phase 3 clinical trial, ORAL Solo (1045),

Tasocitinib is manufactured by Pfizer. The drug is an oral JAK (Janus kinase) inhibitor. The experimental pill reduced inflammation and pain symptoms for 71% of trial patients; inflammation was reduced by at least 20% after a six-month period. Although both types of cholesterol were raised in patients taking the experimental medication, heart attack and stroke rates did not increase.

During the Solo Trial, a six-month, double-blind, placebo-controlled study of 611 randomized patients, 4.1% of them experienced serious adverse events. Although cholesterol levels increased and neutrophil counts and hemoglobin decreased, these changes subsequently stabilized and no new adverse events which could undermine the drug's safety were identified. The trial involved patients who had had an inadequate response to one or more DMARD (disease-modifying antirheumatic drug).

Participants who had been on a placebo during the initial three months were randomized to be given tasocitinib 5mg or 10mg blindly.

Roy Fleischmann, MD, Clinical Professor in the Department of Internal Medicine at the University of Texas Southwestern Medical Center, Dallas, said, in a press release:

“We are encouraged by the statistically significant and clinically meaningful improvements we observed in a proportion of patients treated with tasocitinib monotherapy in ORAL Solo. Further research into additional treatment options for patients with moderately to severely active RA is important, and we look forward to seeing the results of the additional Phase 3 ORAL trials of tasocitinib.”

Pfizer said the Oral Sequel (1024) follow-up Phase 2/3 Trial had demonstrated safety data “consistent with the global Phase 2 RA clinical program.” Tasocitinib administered on its own or together with methotrexate demonstrated a sustained efficacy over a 24-month period.

Trial results were scheduled to be presented at the American College of Rheumatology Annual Meeting.

Tasocitinib had three primary endpoints, of which two were met. Signs and symptoms of rheumatoid arthritis were significantly reduced. Physical function was shown to improve.

Although there was an increase in disease remission, this last measure was not statistically significant. Experts believe a sizeable number of patients who don't want repeated anti-TNF injections, or have not responded well to anti-TNF medications will be candidates for tasocitinib, even if head-to-head tests planned for next year do not demonstrate safety and efficacy superiority, according to a press release.

Current rheumatoid arthritis medications are directed at extracellular targets, such as pro-inflammatory cytokines. Tasocitinib has a new approach "..it targets the intracellular signaling pathways that operate as hubs in the inflammatory cytokine network.”

Pfizer is studying tasocitinib in one of the largest clinical programs of its kind, evaluating more than 4,000 RA patients. The Phase 3 ORAL Trials clinical program includes six studies with more than 350 locations in 35 countries worldwide.

The company is also investigating tasocintinib's potential for psoriasis therapy, as well as ulcerative colitis, Crohn's disease, and organ transplants.

Source: Pfizer

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What do you think of Tasocitinib’s approach in targeting the intracellular signaling pathways that operate as hubs in the inflammatory cytokine network?