Successful Clinical Trial for Pfizer Rheumatoid Arthritis Drug Tasocitinib
Results of a large Phase III clinical trial involving an experimental drug for rheumatoid arthritis was presented this week at the annual meeting of the American College of Rheumatology. Tasocitinib met two of its primary goals and demonstrated good, yet statistically insignificant, results in a third.
Tasocitinib Resulted in 20-70 Percent Improvement in Disease Activity
Tasocitinib (CP-690,550) belongs to a new class of medications known as JAK (janus kinase) inhibitors which targets the signaling of proteins involved in inflammatory and autoimmune diseases. Currently, treatment options for RA are biologic injectables, but tasocitinib is an oral medication which is likely to be more convenient for patients.
The clinical trial, conducted by primary investigator Dr. Roy Fleischmann of the University of Texas Southwestern Medical Center in Dallas, involved 611 patients who received either a 10 milligram dose, a five milligram dose or a placebo twice a day. All patients in the study had active moderate-to-severe rheumatoid arthritis following an inadequate response to prior treatment with at least one other drug.
The study’s first primary goal was to achieve ACR20, meaning the drug provided at least a 20 percent improvement in disease activity and symptoms after three months of treatment. Almost 66% of patients who received 10 milligrams of tasocitinib achieved ACR20, while only 26.7% achieved the goal on a placebo. Of those taking a 5 milligram dose, nearly 60% achieved a 20% improvement.
Tasocitinib also achieved ACR70 – a 70% improvement in disease activity – in 20.3% of patients on the 10 milligram dose and in 15.4% of those on the 5 milligram pill.
The second primary goal was measured using a patient-reported gauge of the improvement to physical functions called HAQ-DI (Health Assessment Questionnaire-Disability Index). On a scale from 0 to 3, lower numbers (0 to 0.5) indicate normal function. On average, patients began the trial with an average score of 1.5, representing moderate to severe function limitation. Patients receiving 10mg of tasocitinib experienced a drop of 0.57 while patients on 5mg reported a 0.5 point improvement.
The third goal of tasocitinib was to demonstrate a numerically higher measure of disease remission at three months using the Disease Activity Scale-28 (DAS-28). While improvements were noted, the researchers say that the difference did not reach statistical significance.
"When it works, it really works," said Fleischmann. "This is the first oral medication for rheumatoid arthritis that has had a successful Phase III study this century."
Serious adverse events were reported in 4% of patients, with six cases of serious infection during the six-month study. Less serious adverse effects included decreases in white blood cells and increases in LDL cholesterol levels. Fleischmann describes the risk profile as “very reasonable” and “relatively small”.
Pfizer is also testing tasocitinib for psoriasis, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), and to suppress the immune system for organ transplantation.
Fleischmann R, et al "Phase 3 study of oral JAK inhibitor tasocitinib (CP-690,550) monotherapy in patients with active rheumatoid arthritis" ACR 2010; Abstract L8.
More presentations from the annual meeting of the American College of Rheumatology this week include:
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