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Trubion Pharmaceuticals Announces Presentation Of Positive Data From Phase IIb And Re-treatment Studies With TRU-015 In Patients With Arthritis

Main Category: Arthritis News
Article Date: 09 Nov 2007 - 0:00 PST



Trubion Pharmaceuticals Inc. (Nasdaq: TRBN) announced presentation of positive data from a Phase IIb study that showed that Trubion's TRU-015 for rheumatoid arthritis (RA) provided statistically significant efficacy after a single infusion of 800 mg or 1,600 mg. In addition, Trubion also announced presentation of data showing that repeat administration with TRU-015 was well tolerated and resulted in a consistent pharmacokinetic (PK) and pharmacodynamic (PD) profile. Trubion is co-developing TRU-015 with Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), for the treatment of rheumatoid arthritis.

"TRU-015's ability to significantly improve RA signs and symptoms following a single infusion could represent a new level of convenience for patients and physicians. These results also suggest that clinical responses may be maintained during B-cell recovery," said Peter Thompson, M.D., FACP, president, chief executive officer and chairman of Trubion. "We and our partner have agreed on a design for our next study that we believe could be supportive of a registration package, and we look forward to TRU-015's continued evaluation."

TRU-015 Improves RA Disease Activity in Phase II Trial (ACR Presentation L7)

On Sept. 10, 2007, Trubion announced preliminary analysis of results for its TRU-015 Phase IIb randomized, double-blind, placebo-controlled, multicenter clinical trial that included 276 patients with rheumatoid arthritis. Patients were randomized equally into five groups that received either placebo, 200 mg, 400 mg, 800 mg or 1,600 mg of TRU-015. The study was designed to evaluate the safety and efficacy of a single intravenous infusion of TRU-015 compared to placebo for a 24-week period.

Data announced previously showed the improvement in DAS-28 compared to placebo was statistically significant in the 800 mg dose group at 12 weeks and at all subsequent assessments, and in the 1,600 mg dose group at 16 weeks and at all subsequent assessments. At 24 weeks, ACR 20, 50 and 70 response rates in the 800 mg dose group were 65 percent, 26 percent and 0 percent, respectively. ACR 20, 50 and 70 response rates in the 1,600 mg dose group were 61 percent, 13 percent and 4 percent, respectively. ACR 20, 50 and 70 response rates at 24 weeks in the placebo group were 33 percent, 9 percent and 2 percent, respectively.

At 24 weeks, significant improvement in the Health Assessment Questionnaire Disability Index (HAQ DI) was observed in the TRU-015 1,600 mg group (-0.70 v -0.37 [p=0.008]) and the 800 mg group (-0.64 v-0.37 [p=0.035]). The HAQ DI measures patients' physical function in defined activities. Median C-Reactive Protein (CRP) improvement was 57 percent in the 1,600 mg group, 48 percent in the 800 mg group and 28 percent in the placebo group. The CRP test measures the concentration of a protein that is present during inflammatory episodes.

TRU-015 administered as a single dose was generally well tolerated, and only one subject in the 400 mg group experienced a grade 3 adverse event on the day of infusion.

Comparable Data Following Repeat Administration (ACR Presentation 309)

The objective of the re-treatment study was to evaluate the safety, PD, PK and immunogenicity of TRU-015 for RA with repeated doses after receiving initial administration in a Phase I/IIa study. Patients treated with a single course of 5 mg/kg or higher in a previously conducted TRU-015 Phase I/IIa study were eligible for re-treatment. Patients who received a single infusion of 5 mg/kg received a single infusion of 5 mg/kg upon re-treatment, and those who received higher doses of TRU-015 received a single infusion of 15 mg/kg upon re-treatment. PD response of B-cells was also evaluated after initial treatment and after re-treatment.

Fifty-four patients were eligible for re-treatment, and at the time of this analysis, re-treatment data were available for 36 patients. B-cell depletion and recovery following re-treatment with TRU-015 was comparable to that seen after initial treatment. Ongoing patient evaluations showed maintenance of ACR responses with repeated single doses of TRU-015 at six-month intervals through at least two retreatment courses. Total serum IgG levels remained within normal limits. In addition, subjects treated with three or more courses of therapy experienced persistent decreases in rheumatoid factor and IgM levels without experiencing decreases in IgG or IgA levels. No neutralizing antibodies to TRU-015 had been detected at the time of this assessment.

Re-treatment with TRU-015 was generally well tolerated, and no grade 3 or 4 adverse events occurred on the day of infusion.

TRU-015 Clinical Development

Trubion and Wyeth have agreed on the design of the next clinical trial, and both companies are working to finalize protocol details and plans for study initiation. The randomized, double-blind, placebo-controlled, multicenter trial will examine ways to further optimize efficacy while evaluating dosing schedule. Additional study protocol details will be provided after commencement of patient dosing.
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