At the American College of Rheumatology Annual Scientific Meeting this November, researchers presented positive findings on several drugs already available on the market. Additionally, there were several studies presented showing positive findings for experimental drugs in various stages of testing. These drugs still have to go through additional Phase II and Phase III studies and only one has been submitted for FDA approval so far. But if safety and efficacy testing continues to show positive results, RA suffers may have more options for treatment in the next several years.
As background, phase II studies are medium sized studies involving up to several hundred patients. They last several months up to two years and focus on the efficacy and safety of a drug. Phase III studies are large scale studies on several hundred to several thousand patients, often lasting several years. The goal of the studies is to build on earlier phases of testing to determine the efficacy, safety and possible side effects of the drug. When drugs successfully complete Phase III testing, the manufacturer can apply for FDA approval for marketing of the drug.
First, Biogen Idec presented Phase II clinical trial results at the ACR meeting showing that it's drug, baminercept caused meaningful improvements in ACR scores (the American College of Rheumatology core set of outcome measures for RA trials) and individual core set measurements in patients with RA who received baminercept compared with placebo. Baminercept is a novel drug, being the first dual-mechanism, lymphotoxin-β (LT-β) and LIGHT pathway inhibitor in development for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). LTα1ß2 and LIGHT are two components of the LT-β pathway, which plays a role in the progression of RA and other autoimmune disorders such as multiple sclerosis, lupus, and Crohn's disease. Scientists think that baminercept inhibits the formation and maintenance of ectopic lymphoid structures associated with autoimmune disease.
Patients who were given the highest doses of 1 mg/kg or 3 mg/kg showed improvements in the outcome measures that lasted up to 8 weeks following the final dose. At day 35, patients given the agent showed an average 60% improvement from baseline in swollen joint count and 47% improvement in tender joint count, compared with 4.6% and 6.7% with placebo, respectively. The researchers reported no serious adverse events from administration of the drug.
The trial was conducted to assess the safety, method of action and efficacy of baminercept with methotrexate, at different dose ranges. Forty-seven patients were randomized in a dose-escalating fashion to receive placebo or one of six doses of baminercept 0.01 mg/kg to 3 mg/kg once-weekly for 4 weeks, followed by 8 weeks of observation. Patients must have received methotrexate for at least 3 months prior to enrollment and continued to receive a stable dose of methotrexate for the entire study period.
Also in the news, the Belgian pharmaceutical group UCB presented data showing that its drug, Cimzia, significantly reduces joint damage from RA and that a high dosage (400 mg injection every other week) may even act to repair joints. The randomized trials studied Cimzia in combination with methotrexate and like most of the other studies with this comparison, found that it was more effective together than methotrexate alone. The study showed that it inhibits the progression of joint damage for up to one year. Cimzia in an anti-TNF inhibitor, like Enbrel, Remicade and Humira.
Cimzia is not without its problems though. UCB has already filed the drug for approval in both the US and EU for the treatment of Chrohn's disease. But recently the EMEA (European Agency for the Evaluation of Medicinal Products), Committee for Medicinal Products for Human Use (CHMP) gave a negative opinion on Cimzia, as treatment for Crohn's disease. UCB will have to address several specific issues raised by the CHMP in order to gain approval by mid-2008. The company has said it will submit an appeal on the decision. And earlier this year, in March 2007, the FDA told UCB that it will need to conduct another trial of patient's clinical response to Cimzia for the treatment of Crohn's disease before approval of the drug can be reconsidered. These negative responses from government regulatory agencies will delay Cimzia for possibly several years. Plus, even if it is approved for Chrohn's disease first, it is possibly several years away from approval for RA. Since it is so far behind the other three established anti-TNF inhibitors, it will have to show some pretty great results in order to gain a following of patients and physicians.
Published On: December 10, 2007