Rx Report†

A new injectable antibiotic, ceftaroline fosamil (Teflaro), has been approved by the United States (U.S.) Food and Drug Administration (FDA) to treat adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI), including methicillin-resistant Staphylococcus aureus (MRSA).1 A dosage adjustment is necessary in patients with moderately impaired renal function (CrCl 30 mL/min to < 50 mL/min) or severely impaired renal function (CrCl < 30 mL/min).2 The most common side effects in trials were diarrhea, nausea, and rash.

Daptomycin for injection (Cubicin) was recently FDA-approved as a oncedaily two-minute intravenous (IV) injection.3 Previously it was approved as a 30-minute infusion for treating MRSA-complicated skin infections and bacteremia.

Atrasentan (Xinlay), a highly selective endothelin-A receptor antagonist (SERA), which antagonizes the effect of endothelin-l (ET-l), led to reductions in residual albuminuria in diabetic nephropathy patients when added to angiotensin receptor blocker or angiotensin-converting-enzyme inhibitor therapy.4 The middle atrasentan dose reduced the urine albumin-to-creatinine (UACR) ratio by 42% compared with reductions of 34% and 21% with the highest and lowest doses, respectively.5 Half the patients who received the middle dose also realized a >40% reduction in UACR from baseline versus 17% for placebo-treated patients.

Bardoxolone, a first-in-class antioxidant inflammation modulator for treating chronic kidney disease (CKD), was shown in mid-stage clinical trials to significantly improve renal function in patients with CKD and type 2 diabetes mellitus (T2DM).6 Phase 3 clinical trials are expected to be started soon.

A complete response letter related to the potential approval of exenatide extended-release for injectable suspension (Bydureon), was received by its manufacturer on October 19, 2010.7 The FDA has requested that exenatide extended-release undergo a comprehensive QT study at higher dose exposure levels to determine the effect of the drug on patient heart rate.8 The dose to be studied will be supratherapeutic. Additional efficacy data from studies already conducted were also requested by the FDA. It is anticipated that the response to the FDA letter will be completed by the end of 2011. It is intended for once-weekly injection.

Ferric citrate (Zerenex) is currently in Phase 3 clinical trials to treat hyperphosphatemia in end-stage renal disease (ESRD) patients on dialysis.9 The strength of this oral formulation is 1 gram. Patients who received 6 grams of ferric citrate daily had a decrease in serum phosphorous levels of 25% after 28 days, those who took 8 grams had a 29% drop in 28 days, and those who took 1 gram daily showed no serum phosphorous reduction. A 58-week study is ongoing. Regulatory filing is anticipated in 2012.

FG-2216, an orally active prolylhydroxylase inhibitor, increased erythropoietin (EPO) production in dialysis patients in a small Phase 1 trial.10 A single 20-mg/kg dose of FG-2216 was administered to dialysis patients with severe renal dysfunction (n = 6), anephric dialysis patients (n = 6), and patients who had normal renal function without major co-morbidities (n = 6). In patients with kidneys, all but one had maximal effects on EPO, 12 hours after dosing. Mean maximal increases were approximately 13-fold in the healthy volunteers and approximately 31-fold in the nephric dialysis patients. This agent is a long way off from Phase 3 efficacy studies but is an interesting prospect.

Fidaxomicin is a new antibiotic for which FDA approval is being sought.11 The proposed indication is for treating Clostridium difficile infection (CDI) and to prevent recurrences of CDI. The new drug application (NDA) was recently submitted, and the manufacturer requested a priority review. If granted, fidaxomicin might potentially receive FDA approval in the second half of this year. In clinical trials, oral findaxomicin dosed twice daily was compared with oral vancomycin dosed four times daily for 10 days. Findaxomicin was well tolerated and shown to be comparable to vancomycin. Also compared with vancomycin, findaxomicin was statistically superior for global cure rates and reducing CDI recurrences by 47%.

Linagliptin is another once-daily oral dipeptidyl peptidase 4 (DPP-4) inhibitor that is currently in Phase 3 clinical trials as monotherapy and combination therapy to manage T2DM.12

PL-56 (Nefecon) has received Orphan Drug Designation for treating IgA nephropathy, also known as Berger's disease.13 The agent is currently in Phase 2 clinical trials. PL-56 is an oral small molecule that downregulates inflammation in the kidneys.

Peginesatide (Hematide) is undergoing clinical trials for the treatment of anemia in chronic renal failure patients receiving dialysis.14 Peginesatide is a synthetic PEGylated peptidic compound that binds to and activates the EPO receptor and acts as an erythrocyte- stimulating agent. An NDA is planned for the second half of 2011. Commercialization is planned within and outside the United States.

Torezolid phosphate is an oral and IV antibiotic in Phase 3 clinical trials for treating ABSSSI.15 It is dosed 200 mg, once a day for six days. This dosing regimen is four days shorter and with a longer dosing interval compared with linezolid, a first-generation oxazolidinone. Torezolid is a second-generation oxazolidinone with activity against gram-positive pathogens, including MRSA.