Product showcase, February 2013
New approvals, indications, and formulations
- The first microsomal triglyceride transfer protein (MTP) inhibitor, lomitapide (Juxtapid—Aegerion), has been approved by FDA as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce LDL cholesterol, total cholesterol, apolipoprotein B, and non-HDL cholesterol in patients with homozygous familial hypercholesterolemia. Inhibiting MTP reduces the level of cholesterol that the liver and intestines assemble and secrete into the bloodstream.
Approval was based on data from a Phase III, open-label trial that evaluated the use of lomitapide in 29 adult patients with homozygous familial hypercholesterolemia. Results from the study showed that when lomitapide was added onto existing lipid-lowering treatment, LDL cholesterol was significantly reduced from a baseline average of 336 mg/dL to 190 mg/dL at week 26.
The drug was approved with a boxed warning citing the risk of hepatotoxicity. Because of the risk of liver toxicity, lomitapide will only be available through the restricted Juxtapid Risk Evaluation and Mitigation Strategy (REMS) Program.
- FDA announced the approval of teduglutide (Gattex—NPS), an analog of glucagon-like peptide 2, to treat short bowel syndrome in adult patients who need additional nutrition from I.V. parenteral nutrition. Teduglutide improves intestinal rehabilitation by promoting mucosal growth and possibly by restoring gastric emptying and secretion, thereby reducing intestinal losses and promoting intestinal absorption.
Approval was based on data from four trials which showed that treatment with teduglutide reduced the volume of weekly parenteral nutrition needed. Abdominal pain, injection-site reactions, nausea, headaches, abdominal distension, and upper respiratory tract infection were the most common adverse events in the trials. FDA noted that the drug is being approved with a REMS to ensure that the benefits of therapy outweigh the risks.
- Varicella zoster immune globulin (Varizig—Cangene) was recently approved by FDA for reducing the severity of chickenpox infections in high-risk individuals when given within 4 days after exposure. The product is indicated for immune-compromised children and adults, newborns, pregnant women, premature infants, children younger than 1 year old, and adults with no immunity to varicella zoster virus (VZV). The immune globulin is administered in two or more injections, depending on the weight of the recipient, within 96 hours after exposure.
FDA noted that this product has been available under an investigational expanded access protocol during the licensing process. Data collected from individuals treated under the protocol showed a lower rate of severe VZV infection in susceptible individuals compared with the rate in untreated individuals. The studies also showed the product to be safe, with the most common adverse effects being pain at the injection site and headache.
- Abiraterone (Zytiga—Janssen) has been approved for use in men with late-stage (metastatic), castration-resistant prostate cancer prior to receiving chemotherapy. The drug was initially approved for use in men whose prostate cancer progressed after treatment with docetaxel.
Approval was based on a double-blind study involving 1,088 men with late-stage, castration-resistant prostate cancer who had not previously received chemotherapy. Results showed that radiographic progression-free survival was 16.5 months with abiraterone and 8.3 months with prednisone alone (P < 0.001). In addition, over a median follow-up period of 22.2 months, overall survival was improved with abiraterone (median not reached vs. 27.2 months for prednisone alone, P = 0.01). (See page 32 for more information.)
- FDA announced that it has expanded the approval of oseltamivir (Tamiflu—Roche) to treat pediatric patients as young as 2 weeks who have shown symptoms of influenza for no longer than 2 days. The agency noted that the drug is not approved to prevent influenza in this population.
The expanded approval was based on extrapolation of data from previous study results in adults and older children, as well as additional supporting safety and pharmacokinetic studies. FDA noted that dosing for children younger than 1 year must be calculated for each patient based on their exact weight. These children should receive 3 mg/kg twice daily for 5 days. These smaller doses will require a different dispenser than what is currently copackaged with the drug.
- Biotest announced FDA approval of immune globulin intravenous (human) 10% liquid (Bivigam) for the treatment of patients with primary humoral immunodeficiency (PI). The product is a sugar-free, glycine-stabilized, I.V. immune globulin available in 50-mL (5-g) and 100-mL (10-g) tamper-evident vials.
Biotest noted that the product uses a label with an integrated hanger, that the packaging material is latex free, and that this is the first polyspecific intravenous immune globulin they are manufacturing in the United States. They plan to eventually produce up to 1.5 million g (1.5 tons) of immune globulin in the U.S. facility.
- Alexza announced FDA approval of loxapine (Adasuve) inhalation powder for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. Loxapine is an antipsychotic agent that is already marketed in capsule form. Alexza noted that this new formulation of loxapine uses the company’s proprietary Staccato delivery system, which is a hand-held inhaler that delivers a drug aerosol to the deep lung, resulting in rapid systemic delivery and absorption.
Data from two Phase III trials showed that a dose of loxapine 10 mg resulted in statistically significant reductions in agitation, with effects apparent as early as 10 minutes following administration as compared with placebo.
Alexza noted that the product can cause bronchospasm that has the potential to lead to respiratory distress and respiratory arrest. The drug will only be available through the Adasuve REMS restricted program and can only be administered in health care facilities with immediate access to on-site equipment and personnel trained to manage acute bronchospasm.
- Endo announced the launch of its reformulated, crush-resistant oxymorphone extended-release tablets (Opana ER) in two new strengths, 7.5 mg and 15 mg. According to surveillance data, the reformulated design correlated to reduced abuse rates compared with the non–crush-resistant version discontinued in May.
The launch of these two additional dosage strengths add to the five reformulated crush-resistant strengths already on the market: 5 mg, 10 mg, 20 mg, 30 mg, and 40 mg.