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Explore This IssueAugust 2014
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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.
Reported at EULAR, patients fared better in early (less than two years in duration) RA outcomes when treated with a combination of 8 mg monthly tocilizumab plus methotrexate (MTX) than with either agent as monotherapy, during this 104-week study.7 The Health Assessment Questionnaire Disability Index (HAQ-DI) was used to assess outcomes. Patients were randomized to received tocilizumab 4 mg or 8 mg once monthly plus MTX, monotherapy with 8 mg tocilizumab monthly or MTX monotherapy.8 Most patients were women with a mean age of 50 years. The short form (SF)–36 measured changes from baseline from the evaluated time points. A 100 mm visual analog scale was used in which baseline pain scores were around 60 and patient global assessments were around 65. This was a Phase 3 trial, FUNCTION, which included 1,157 methotrexate-naive patients. Improvements on rating scales were noted as early as two weeks into therapy and were highest for the 8 mg tocilizumab-plus-MTX group. By the end of Year 1, combination-therapy-treated patients had decreases of 43 points on the pain scale and 46 points on the patient-reported global assessment compared with MTX-monotherapy patients of 35 and 37 points, respectively. ACR-defined responders included 68% on combination therapy, 60% on tocilizumab monotherapy and 52% on MTX monotherapy. MTX-naive early RA patients showed improvement across all patient-reported outcomes, including physical function, fatigue, pain and quality of life, with combination-therapy-treated patients showing unfailingly greater numerical improvements compared with MTX-monotherapy-treated patients.
Femoral fractures have been linked to bisphosphonates. This adherence study evaluated Medicare, fee-for-service, female (n=522, 287) beneficiaries from 2006–2010.9 Medication possession ratio (MPR) was used as a measure of medication adherence. An MPR of less than one-third was considered to be less compliant. An MPR greater than or equal to one-third or less than two-thirds was considered adherent, and an MPR greater than two-thirds was considered highly adherent. Alternative cutoff points at 50% and 80% were also used. Cumulative incidence and hazard of subtrochanteric/femoral shaft (ST/FS) or intertrochanteric/femoral neck (IT/FN) fractures were also determined. A graded increase in the incidence of ST/FS fractures was noted as the adherence level increased (Gray’s test, P < 0.001). The researchers estimated that during the fourth year of bisphosphonate treatment there was an increase of 76 per 100,000 in the rate of ST/FS fractures and a decrease of 312 per 100,000 in the rate of IT/FN fractures. The authors believed that these study results support the hypothesis that cumulative exposure to oral bisphosphonates may be causally related to ST/FS fractures.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in NYC, and a pharmacist at New York Presbyterian—Lower Manhattan Hospital.
- Dekavil (F8-IL10). Philogen. http://www.philogen.com/DEKAVIL.html.
- Galeazzi M, Bazzichi G, Sebastian G, et al. A phase Ib clinical trial in rheumatoid arthritis of Dekavil (F8-IL10), a novel anti-inflammatory immunocytokine. EULAR 2014. Abstract SAT0232.
- Combination Therapy of F8IL10 and Methotrexate in Rheumatoid Arthritis Patients. Clinical Trials. June 18, 2014. http://clinicaltrials.gov/ct2/show/NCT02076659.
- Barber J. FDA delays decision for Orexigen’s experimental obesity drug, shares fall. First Word Pharma. June 11, 2014. http://www.firstwordpharma.com/print/1216650?tsid=17.
- Chavis R. Mylan launches generic Actonel tables. Drug Store News. June 11, 2014. http://www.drugstorenews.com/article/mylan-launches-generic-actonel-tablets.
- UCB announces data from first seven year evaluation for Cimzia® (certolizumab pegol) in moderate to severe Crohn’s disease patients. May 5, 2014. http://www.prnewswire.com/news-releases/ucb-announces-data-from-first-seven-year-evaluation-of-cimzia-certolizumab-pegol-in-moderate-to-severe-crohns-disease-patients-257934701.html.
- Walsh N. Combo therapy boosts patient outcomes in RA. June 14, 2014. http://www.medpagetoday.com/MeetingCoverage/EULAR/46316.
- Burmester G, Bianco R, Keiserman M, et al. Tocilizumab (TCZ) as combination therapy and as monotherapy versus methotrexate in MTX-naive patients with early rheumatoid arthritis: Patient-reported outcomes (PROS) from a randomized, placebo-controlled trial. EULAR 2014. Abstract SAT0226.
- Garrett N. Bisphosphonate compliance linked to increase in femoral fractures. Rheumatology Update. June 4, 2014. http://www.rheumatologyupdate.com.au/latest-news/bisphosphonate-compliance-linked-to-increase-in-fe.