Galapagos NV has announced that the first rheumatoid arthritis (RA) patients have been screened for enrolment in the Phase 2B clinical program with GLPG0634, a selective JAK1 inhibitor.
The DARWIN Phase 2B program includes two dose finding studies and an open label extension study. The dose finding studies will evaluate the efficacy and safety of GLPG0634 with 24 weeks of treatment in 875 moderate to severe RA patients refractory to methotrexate.
GLPG0634 is the first selective JAK1 inhibitor in development for RA. The results of two 4-week Phase 2A clinical studies demonstrated the rapid clinical benefit and favorable safety profile of the drug, and supported the selection of the GLPG0634 doses that will be evaluated in the current Phase 2B program.
Galapagos started the 24-week global DARWIN Phase 2B program in RA to identify the dose and dose-regimen that offers optimal efficacy and safety of GLPG0634 in patients with moderate to severe RA.
Galapagos expects to report completion of recruitment by mid-2014 and 12-week topline data from the Phase 2B program in Q4 2014.
"GLPG0634 has shown a rapid suppression of disease activity with a good safety profile in the 4-week Phase 2A studies in RA patients. We look forward to seeing the effect of GLPG0634 in a global study, for a longer treatment period, and in a larger and more diverse patient population. The first patients will be recruited in Belgium and New Zealand," said Dr Piet Wigerinck, Chief Scientific Officer of Galapagos.
Dr Wigerinck continued, "Galapagos is on track in the RA program and is now also preparing for a Phase 2 study with GLPG0634 in Crohn's disease, which will run in parallel with the Phase 2B study in RA. By early 2014, we will have Phase 2 programs with GLPG0634 in RA and Crohn's, both with final readouts before mid-2015."
Details of the DARWIN Phase 2B program
The Phase 2B program, named DARWIN (Drug Against Rheumatoid Arthritis With Selective JAK1 INhibition) includes 2 dose finding studies, DARWIN 1 and DARWIN 2, and an open label extension study, DARWIN 3.
All patients will have received methotrexate (MTX) but no longer have an adequate therapeutic response to this first-line therapy in RA. Patients will not have been exposed to prior biological treatments.
DARWIN 1 will enroll 595 patients who will continue their stable therapy of MTX while receiving GLPG0634 or placebo, whereas in DARWIN 2, 280 patients will stop MTX and receive monotherapy of GLPG0634 or placebo.
All patients who receive placebo or low dose GLPG0634 and do not show improvement after 12 weeks of treatment will be randomized to a higher dose of GLPG0634.
After completion of 24 weeks in either DARWIN 1 or 2, patients may continue open-label GLPG0634 as part of DARWIN 3, an extension study that will collect long-term safety and efficacy data.
GLPG0634 doses in DARWIN 1 and 2 will be 50, 100 and 200 mg per day. In DARWIN 1, these doses will be given as once-daily and twice-daily regimens (daily doses split in two), whereas only once-daily dosing will be evaluated in DARWIN 2. The DARWIN program will recruit patients from Europe, the Americas, Australia, and New-Zealand.