Affymax and Takeda voluntarily recalled the anemia drug Omontys after three patients taking the drug died. The deaths were caused by serious and life-threatening allergic reactions that occurred in the patients within 30 minutes of receiving the drug by intravenous injection during dialysis treatments for end-stage renal disease. The anaphylactic reactions occurred only in dialysis patients receiving the drug by intravenous injection, not by subcutaneous administration. Approximately 0.2 percent, or 50, of the 25,000 patients receiving the drug in post-marketing studies had serious allergic reactions with roughly a third of those serious enough to require acute medical intervention. Omontys treats anemia that stems from chronic kidney disease by stimulating formation of red blood cells, a process known as erythropoiesis. The drug was approved by the U.S. Food and Drug Administration in March 2012. Alternative erythropoiesis-stimulating agents are available to treat anemia, including Amgen’s Procrit, Epogen, and Aranesp. Letters have been sent to healthcare professionals and dialysis organizations instructing them to stop using the drug for any patient. Prior to February, two deaths occurred. They were reported and attributed to cardiovascular issues. There is no timing on the next steps of the investigation.

Dynavax Technologies’ Biologic License Application for heplisav, an adult hepatitis B vaccine that provides early and high protection with fewer doses compared to existing vaccines, was rejected for further safety assessments before it will be approved for adults 18 to 70 years of age. The FDA is concerned in particular about the safety of the strong adjuvant in such a broad age range, and also that novel adjuvants may cause rare autoimmune events. The adjuvant in heplisav is a short DNA sequence that activates the immune response by specifically targeting Toll-like receptor 9, found on a specialized subset of immune cells and so should selectively activate the immune system. In their complete response letter, the FDA also requested additional data from Dynavax’s process validation program and clarifying information on the manufacturing controls and facilities related to the assurance of the quality of the commercial product. The product is manufactured in Dynavax’s facility in Düsseldorf, Germany.

Patients worldwide with a certain type of newly-diagnosed glioblastoma lost another potential therapy as Merck KGaA announced its late-stage trial of the integrin inhibitor cilengitide did not meet its primary endpoint. The experimental therapy for glioblastomas characterized by a methylated DNA methyltransferase gene promoter did not significantly increase overall survival when added to the current standard regimen of temozolomide in combination with radiotherapy. The trial involved more than 500 patients from 23 countries and was planned and conducted in a partnership with the European Organization for Research and Treatment of Cancer. Integrins are an attractive therapeutic target in cancers because they are involved in cell adhesion and migration and effect blood vessel formation and tumor growth. Blocking integrins with cilengitide inhibits cell invasion and new blood vessel growth but as a single agent has shown to not be effective in treating recurrent glioblastoma. Now the results indicate it is not effective in combination therapy for newly diagnosed glioblastoma either. Patients whose tumors have an unmethylated gene promoter status are currently being evaluated in a mid-stage trial.

Johnson & Johnson must pay $3.35 million in compensatory damages to a woman for years of severe and chronic pain following surgery to implant the Prolift transvaginal mesh. The jurors found that Ethicon, a division of Johnson & Johnson and maker of the implant, failed to properly warn of the risks of vaginal mesh and made fraudulent misrepresentations. This verdict comes nearly one year after the FDA stated in a March 16, 2012 communication to Bloomberg News that the vaginally placed pelvic mesh product, sold by Ethicon since March 2005, was initially marketed without any clearance or approval from the FDA. Johnson & Johnson stopped selling Prolift last year amid mounting lawsuits; there are currently about 4,000 lawsuits alleging harm from the product. Mesh implants, made of a porous synthetic or biologic material, are implanted and tied to ligaments or bone to serve as a sling that lifts and supports the uterus. Hundreds of thousands of women had the implant, with thousands experiencing adverse side effects of severe pain, infections, and bleeding. The current damages were awarded at the end of a one-month trial during which the former nurse cited the inability to work, and severe and chronic pain as a result of the implant and 18 unsuccessful follow-up surgeries to fix it. In this trial, the jurors rejected a claim that the implant was designed defectively. The trial is to begin a second phase next week, in which the jury considers whether to also award punitive damages. Under New Jersey law, punitive damages of up to five times the compensatory damage amount are allowed, bringing the total potential cost for Johnson & Johnson to $20.1 million.

The FDA denied Reckitt Benckiser Pharmaceuticals’ citizen’s petition requesting the agency to adopt more stringent packaging standards and to increase educational interventions in order to help reduce the number of children exposed to buprenorphine-containing products used to treat opioid dependence. Reckitt Benckiser will discontinue the sale and cease distribution of their combination buprenorphine and naloxone sublingual tablets in the U.S. as of March 18 2013 because of their concerns regarding children accidentally taking the drug. “As a pioneer in opioid dependence treatment, Reckitt Benckiser Pharmaceuticals strongly believes that child-resistant, unit-dose packaging and increased educational interventions are in the best interest of public health and safety, and we encourage other manufacturers to proactively implement these additional safeguards,” says Tim Baxter, global medical director for Reckitt Benckiser. The FDA’s rejection notice also mentioned that two unnamed manufacturers have now received approval to produce generic suboxone tablets but the details of these manufacturers’ safety programs were not provided.

The FDA stopped all pediatric clinical trials of Amgen’s parathyroid-regulating drug Sensipar after a 14-year-old patient died in a trial. The drug, approved to treat an over-active parathyroid gland resulting from parathyroid cancer or chronic renal disease in adults, is not approved by the FDA for use in children younger than 18 years old. The complication of secondary hyperparathyroidism can develop early in people with chronic kidney disease and is known to cause problems for people on dialysis. In particular, children on dialysis can have a wide range of bone and growth issues. Too much parathyroid hormone, PTH, can cause brittle bones and kidney stones by increasing the amount of calcium that gets absorbed from the bone and transferred to the blood, but too little PTH can, in turn, lower blood calcium levels dangerously low, causing muscle cramping, convulsions, and burning or prickling sensations. Significant reductions in calcium may even increase the chance of seizures. While the most frequently reported side effects of the drug in adult trials were nausea, vomiting, and diarrhea, the fact that regulation of total serum calcium is different in adults compared to children and adolescents should impose caution on dosages in future clinical trials.

This past week Hospira, the world’s leading provider of injectable drugs and infusion technologies, issued urgent recalls for five different drugs. Specific lots of propofol injectable emulsion, for use in anesthesia or sedation, had visible particles embedded in the glass; preliminary investigations suggest a glass defect. Risks associated with this defect, according to the recall notice, include tissue necrosis in one or more organs that could result in stroke, myocardial infarction, respiratory failure, and loss of renal and hepatic function. Hospira also urgently recalled one lot each of the injectable drugs diazepam, furosemide, succinylcholine chloride, and preservative-free morphine sulfate due to loose crimps or no crimp applied to the flip top vial. These defects may result in a breach of sterility, contamination of the vial contents with bacteria, virus, or fungi, and leakage of contents. Risks associated with contamination include thrombosis, phlebitis, and endocarditis. Injections of contaminated drugs can potentially lead to septic shock, says Hospira, with the potential to be life threatening. Signs and symptoms to watch for include injection site reactions, fever, shortness of breath, tachycardia, and feeling generally ill with nausea and vomiting. Hospira is the sole supplier of diazepam injection in the United States.