New approvals

Abstract

Belatacept, an intravenous (IV) selective T-cell costimulation blocker, has been approved by the Food and Drug Administration (FDA) to prevent kidney rejection in adult transplant recipients, and is to be used in combination with basiliximab induction, corticosteroids, and mycophenolate mofetil for maintenance immunosuppresion.1 Belatacept is to be used only in patients who are Epstein-Barr virus (EBV) positive. Patients who receive treatment with belatacept have an increased risk of developing central nervous system post-transplant lymphoproliferative disorder (PTLD) and/or progressive multifocal leukoencephalopathy (PML). PML occurred in patients receiving higher than recommended doses within an immunosuppressive regimen. Therefore, a risk evaluation and mitigation strategy (REMS) is available to ensure that patients and prescribers know the benefits and risks of therapy. The REMS includes a communication plan for potential prescribers and supportive healthcare professionals, and a medication guide for patients.

Extended-release exenatide (Bydureon), for once-weekly injection, has been approved in Europe to treat type 2 diabetes mellitus.2 In the United States, the FDA issued a complete response letter to the drug's manufacturers asking for additional information on the drug's heart rate effects. A response to this letter is expected in the second half of this year.

Fidaxomicin tablets, an oral macrolide, were recently FDA-approved for treating Clostridium difficile-associated diarrhea (CDAD) in adults.3 In clinical trials, treatment with fidaxomicin was non-inferior to oral vancomycin in sustaining a clinical response for up to 25 days after therapy completion.4 The most common adverse reactions in clinical trials were nausea (11%), vomiting (7%), abdominal pain (6%), gastrointestinal hemorrhage (4%), anemia (2%), and neutropenia (2%).

Production of iron sucrose injection (Venofer) had been temporarily halted related to the presence of particulate matter in some of America Regent's generic injectable products.5 Even though there were no specific quality issues related to iron sucrose injection, for precautionary measures, its manufacturer had stopped production. American Regent re-started production of this agent in mid-May.

At last the long-awaited generic of Levaquin, levofloxacin, has arrived.6 The FDA has approved both the tablets and IV injection dosage forms from many generic companies; therefore the price of this generic will likely be significantly less than if one generic were approved, and also less than the branded product. (Is there a Levaquin XR on the horizon, even though it is already a once-daily agent?) In recent quarterly results, Johnson & Johnson recorded $343 million in revenue from both branded levofloxacin and ofloxacin.

Sodium ferric gluconate complex in sucrose injection has been FDA-approved for treating iron deficiency anemia in adults and children aged 6 years and older who are undergoing chronic hemodialysis and receiving supplemental erythropoietin therapy. It was approved as an AB-rated generic in 62.5-mg single-dose vials (12.5 mg of elemental iron per milliliter).7

Oral bardoxolone has been shown to provide sustained renal function improvement in patients with type 2 diabetes mellitus (T2DM) and moderate-to-severe renal impairment, as measured by estimated glomerular filtration rate (eGFR).8 Bardoxolone methyl is an oral, antioxidant, inflammation modulator currently in Phase 2 clinical trials. In the dose-finding BEAM Study, patients received once daily 25, 75, or 150 mg bardoxolone, or placebo for 52 weeks. Improvements in eGFR were seen in all three active-drug study groups at week 24 (the primary endpoint) and also at week 52. The most common adverse effects were muscle spasm, hypomagnesemia, transient liver function test elevations, and gastrointestinal symptoms. Multinational Phase 3 studies are planned for approximately 1,600 patients with T2DM and chronic kidney disease (CKD).9 The primary study objective is to assess the impact of bardoxolone methyl on clinical outcomes, such as time to dialysis or cardiac death.

Dapagliflozin, an investigation T2DM medication that works by blocking glucose from being absorbed into the bloodstream through the kidneys, is being scrutinized due to a potential increase in certain cancers.10 In a two-year study, more patients treated with the agent developed bladder and breast cancers compared with a control group. Of 5,478 patients treated with dapagliflozin, nine bladder cancers occurred compared with one patient in the control group. With breast cancer, nine of 2,223 women treated with the agent, compared with one patient who received placebo, developed cancer. All of these patients were diagnosed within one year of beginning the study.

The erythropoiesis-stimulating agents (ESAs) are in the news yet again; this time the FDA has modified the prescribing language for the ESAs in managing patients with CKD.11 The modified language is taken from information from the TREAT trial, which showed that when a target hemoglobin level of greater than 11 g/dL for ESAs with CKD was achieved, an increased risk of serious adverse cardiovascular events occurred. Additionally, there was no added patient benefit. The revised labeling in dialysis patients directs physicians to start ESAs when the hemoglobin level is less than 10 g/dL, and guides them to lower or stop dosing when the hemoglobin level approaches or goes higher than 11 g/dL. For non-dialysis CKD patients, the label directs physicians to consider starting ESA therapy when the hemoglobin level is less than 10 g/dL, and that the dose be lowered or stopped if the hemoglobin surpasses 10 g/dL. The FDA is also modifying the existing REMS for the ESA class.