CH-4051, an oral therapy to treat rheumatoid arthritis developed by Chelsea Therapeutics, has shown promise in early phase
CH-4051 is the L-isomer of Chelsea’s pipeline drug CH-1504. It is an orally bioavailable, non-metabolized antifolate. CH-4051 has anti-inflammatory, autoimmune and anti-tumor properties that potently inhibit dihydrofolate reductase, an enzyme required for cell proliferation.
CH-4051 has been found safe in preclinical and clinical studies conducted so far. Data from CH-4051 also suggests the experimental drug candidate has superior safety and tolerability, as well as increased efficacy compared to methotrexate, Chelsea Therapeutics said in a press release.
Currently, methotrexate is the leading antifolate treatment and standard of care for diseases including arthritis, psoriasis, Crohn’s disease, ankylosing spondylitis, uveitus, psoriatic arthritis and several forms of cancer.
Chelsea Therapeutics International, Ltd. announced that it received US FDA approval for a phase 2 study to evaluate the efficacy of CH-4051 in rheumatoid arthritis.
Patient screening for CH-4051 phase 2 studies will begin next month.
The multi-national, randomized phase II trial of CH-4051 will involve 250-patients. The double-blind, head-to-head study will compare the efficacy of CH-4051 against methotrexate.
Three daily oral doses of CH-4051 — 0.3 mg, 1.0 mg, 3.0 mg or 3.0 mg –will be tested with or without folate of CH-4051 or 20 mg weekly dose of plus folate supplement for 12 weeks following a two-week methotrexate-washout in patients with rheumatoid arthritis who are experiencing an inadequate response to methotrexate treatment.
“Although MTX [methotrexate] is considered the standard of care in RA, both as a monotherapy and in combination with other RA treatments, the dosing and maximal therapeutic benefit of MTX is limited by well-documented tolerability issues, long-term safety concerns and variable bioavailability,” stated Dr. Simon Pedder, president and CEO of Chelsea Therapeutics.
“Given that CH-4051 is metabolically stable and that all of our preclinical and clinical work suggests enhanced absorption, dramatically increased potency and improved tolerability over MTX, we believe CH-4051 will be safe and highly efficacious in a historically treatment-resistant patient population,” he added.
Chelsea Therapeutics is a biopharmaceuticals development company.