Pipeline & Drug Approvals
F8-IL10 (Dekavil) is a subcutaneously administered, once-weekly agent consisting of the antiinflammatory cytokine interleukin 10 (IL-10) fused to a vascular targeting antibody (fusion protein).1 In vivo, this agent targets arthritic sites and is, therefore, currently being studied to treat rheumatoid arthritis (RA). In a small Phase 1b study, 14 of 22 patients (64%) with active RA who had failed at least one tumor necrosis factor alpha (TNF-α) inhibitor experienced beneficial results with increasing weekly doses of the agent (doses of six, 15, 30, 60, 110 and 160 mcg/kg were used). Treatment was for eight weeks. All patients received F8-IL10 along with fixed-dose methotrexate (10–15 mg/week). Among those patients who received weekly doses of 15 mcg/kg, 30 mcg/kg or 60 mcg/kg, three had American College of Rheumatology (ACR) 70 responses after seven weeks (14%). During the same time-frame, four had ACR50 responses (18%), and seven had ACR20 responses (32%). Injection-site reactions were common, occurring in 50% of patients; otherwise, F8-IL10 was well tolerated. Fifteen patients were analyzed for autoantibodies to F8-IL10, two patients showed positivity.2 Phase I studies are ongoing and currently recruiting patients.3
NB32 (bupropion/naltrexone, Contrave), an experimental obesity drug, has had its drug application review extended by the Food and Drug Administration (FDA) for another three months (to mid-September). The FDA originally rejected the drug combination in 2011, requesting long-term cardiovascular outcomes studies in obese and overweight subjects. The manufacturer worked with the FDA to develop a study that is ongoing in 8,900 patients. This study provided interim safety and cardiovascular outcomes, which were used in the agent’s resubmission data package to the FDA. The agent is currently under review in Europe.4 Risedronate 150 mg tablets (generic Actonel) for treating postmenopausal osteoporosis were recently launched in the U.S.5
A seven-year, open-label, extension clinical trial, PRECiSE 3 (PEGylated antibody fragment evaluation in Crohn’s disease: safety and efficacy), is evaluating the safety of the anti-TNF-α therapy certolizumab pegol in Crohn’s disease (CD).6 Results were reported recently at the Digestive Diseases Weekly Meeting in Chicago (early May). Certolizumab pegol is also FDA approved for treating RA, psoriatic arthritis and ankylosing spondylitis. This study evaluated 595 patients who received certolizumab pegol 400 mg every four weeks for up to seven years. No new safety signals were identified. Remission in CD ranged from 68–76%. A post-hoc analysis evaluated long-term outcomes in CD, stratifying patients who had received prior anti-TNF-α therapy (n=119) or who were anti-TNF-α therapy naive (n=475). The data suggest that patients who had prior anti-TNF-α therapy, had shorter remissions and a shorter mean duration of response. It is not known whether this information can be extrapolated to other disease states; however, long-term outcomes and safety information about these complex agents are always welcome in assessing patient risk vs. benefit.