Results from the 50-patient placebo-controlled trial demonstrated that three of the four doses of INCB18424 evaluated (15mg BID, 25mg BID and 50mg QD) produced impressive clinical benefits and all of the doses were well tolerated.
American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 response rates in the three most effective dose groups ranged from 50% to 83%, 40% to 50%, 25% to 30%, 10% to 17% respectively, and were achieved in one month, with responses seen as early as one week, the company said. Although there have been no head-to-head comparator trials, ACR 20/50/70 response rates with existing injectable biologic agents in larger studies typically average 60%/40%/20%, respectively, after three to six months of therapy.
Based on these 28-day Phase IIa results, two six-month Phase IIb trials using a similar range of doses are expected to begin in the fourth quarter of 2008. The first trial is expected to involve eight treatment arms and 280 rheumatoid arthritis (RA) patients who are receiving disease modifying therapy but whose disease is not adequately controlled. The second trial is expected to include 140 patients previously treated with anti-tumour necrosis factor therapies for at least eight weeks.
Larry Moreland, principal investigator of the study, said: “Results from this initial Phase IIa trial suggest that INCB18424, a novel oral janus kinase inhibitor, has the potential to be at least as effective as currently available RA therapies, including the widely used injectable biologicals. I look forward to participating in the next phase of clinical trials and seeing this new class of potent oral anti-inflammatory agents with an exciting mechanism of action progress through clinical development.”