TD-1473 showed a reduction in plasma exposure compared to?currently-approved JAK inhibitor.
On June 9, 2016, Theravance Biopharma released positive results from a completed Phase I clinical trial of TD-1473, its oral GI-targeted pan-Janus kinase (JAK) inhibitor. TD-1473 is specifically designed to penetrate the intestinal wall and act directly at the site of inflammation with minimal systemic exposure.
According to the press release, the trial was a randomized, double-blind, placebo-controlled, single ascending dose and multiple ascending dose study in healthy subjects.
Data from the Phase I trial showed that TD-1473 was generally safe and well tolerated as a single dose (up to 1000 mg) and as a daily dose (up to 300 mg) given for 14 days. For subjects who were administered TD-1473, there were no reports of serious adverse events (AEs) and AEs that were reported were considered mild in severity and short in duration.? No AEs were reported to have led to study discontinuation. ?
No clinically significant changes were observed for either ECG variance from baseline or laboratory findings relative to placebo.
In addition,?the study clarified the amount of drug detected in systemic circulation following oral administration, which is of interest because there are a range of safety and tolerability concerns associated with systemically available JAK inhibitors.?
Plasma exposures of TD-1473 at daily doses of 30 mg and 100 mg were approximately 75-fold and 15-fold lower, respectively, as compared to the plasma exposure of tofacitinib at twice daily doses of 10 mg.? (Read more about tofacitinib below.)
Brett Haumann, MD, Chief Medical Officer at Theravance Biopharma said, “We are encouraged by the data from this initial clinical trial of TD-1473, as they provide validation for our strategy of targeting JAK inhibition to the affected tissues within the GI tract in order to achieve desired therapeutic results with a favorable safety and tolerability profile.”
Based on the study results, the Company intends to initiate a Phase 1b clinical trial of TD-1473 in patients with ulcerative colitis later in 2016.
Tofacitinib is a JAK inhibitor that was discovered and developed by the National Institutes of Health and Pfizer and is approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. According to the Prescribing Information, tofacitinib may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs) and there is an ongoing development program in ulcerative colitis.