Approvals of drugs to treat seizures, chronic hepatitis C virus infection, depression


Approvals

The first generic versions of rabeprazole sodium (Aciphex) delayed-release tablets, used to treat gastroesophageal reflux disease in adults and adolescents.

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The first generic versions of aduloxetine (Cymbalta) delayed-release capsules to treat depression and other conditions.

Simeprevir (Olysio), to treat chronic hepatitis C virus infection . A protease inhibitor, it is to be used as a component of combination antiviral treatment in adults with compensated liver disease, including cirrhosis. Safety and effectiveness were evaluated in studies of 2,026 participants, in which 80% of treatment-naive participants given the drug as part of combination therapy sustained virologic response, compared to 50% of those not receiving the drug. It also improved response in treatment-experienced participants. A reduction in effectiveness was observed in participants with an NS3 Q80K polymorphism, so the drug label includes a recommendation to screen for the presence of that strain prior to therapy. The most common side effects were rash (including photosensitivity), pruritis and nausea.

Eslicarbazepine acetate (Aptiom) to treat seizures in adults . It is approved as an add-on medication to treat partial seizures associated with epilepsy. In 3 randomized clinical studies, the drug reduced the frequency of seizures compared to placebo. The most common side effects included dizziness, drowsiness, nausea, headache, double-vision, vomiting, fatigue and loss of coordination. Like other antiepileptic drugs, it may cause suicidal thoughts or actions in a very small number of people.

The RNS Stimulator, a medical device to treat epilepsy . It consists of a small neurostimulator implanted within the skull under the scalp and is intended to reduce frequency of seizures in epilepsy patients who have not responded well to medications. Approval is based on a randomized trial of 191 patients which showed a 34% reduction in the average number of seizures per month with the device turned on compared to a 19% reduction with it turned off. Patients with the device cannot undergo MRI, diathermy procedures, electroconvulsive therapy or transcranial magnetic stimulation. The most frequent adverse events were implant site infection and premature battery depletion.

A new indication for collagenase clostridium histolyticum (Xiaflex) as the first non-surgical treatment for Peyronie's disease . A treatment course of this biologic medicine consists of a maximum of 4 treatment cycles, each with 2 injection procedures and 1 penile modeling procedure. Safety and effectiveness were established in trials of 832 men in which the drug significantly reduced penile curvature deformity compared with placebo. The drug was approved for Dupuytren's contracture in 2010. For Peyronie's disease, it is available only through a restricted program because of the risks of serious adverse reactions, including penile fracture and other serious penile injury. The most common adverse reactions included penile hematoma, penile swelling and penile pain.

Four diagnostic devices for high throughput gene sequencing. These instruments, reagents, and test systems allow labs to sequence a patient's DNA. Two of the devices are used to detect DNA changes in a gene which can result in cystic fibrosis, and the other 2 make up the first FDA-regulated test system that allows laboratories to develop and validate sequencing of any part of a patient's genome.

Influenza A (H5N1) virus monovalent vaccine, the first adjuvanted vaccine to prevent H5N1 avian influenza in people 18 and older. The vaccine is not intended for commercial availability and has been purchased by the U.S. government for distribution by public health officials if needed. It is made using an egg-based manufacturing process and is administered via intramuscular injection in 2 doses, 21 days apart. Safety and effectiveness were evaluated in a trial of about 3,400 adults in which 91% of individuals between 18 and 64 years and 74% of individuals 65 years and older who received the vaccine developed antibodies at a level that is expected to reduce the risk of getting influenza.

Ibrutinib (Imbruvica) to treat mantle cell lymphoma (MCL), a rare form of non-Hodgkin's lymphoma. The drug is intended for patients with MCL who have received at least one prior therapy. Approval is based on a study of 111 participants, who had a nearly 66% response rate. An improvement in survival or disease-related symptoms has not been established. The most common side effects are thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, edema, upper respiratory infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting and decreased appetite. Other clinically significant side effects include bleeding, infections, kidney problems and other types of cancers.

A new indication for sorafenib (Nexavar) to treat metastatic differentiated thyroid cancer. Safety and effectiveness were established in a study involving 417 participants, in which the drug increased progression-free survival by 41%. The most common side effects were diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains and hypertension. The FDA approved sorafenib to treat advanced kidney cancer in 2005 and liver cancer that cannot be surgically removed in 2007.

Hydrocodone bitartrate extended-release capsules (Zohydro ER) for the management of pain severe enough to require daily, around-the-clock, long-term treatment and for which alternative treatment options are inadequate. The schedule II controlled substance is the first FDA-approved single-entity and extended-release hydrocodone product. Safety and efficacy were based on studies of patients with chronic pain, who showed significant improvement compared to placebo. The most common side effects were constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting and pruritus. The drug will be part of the Extended-Release/Long-Acting Opioid Analgesics Risk Evaluation and Mitigation Strategy.

Riociguat (Adempas) to treat 2 forms of pulmonary hypertension: chronic thromboembolic pulmonary hypertension (after surgery or in patients who cannot undergo surgery) and pulmonary arterial hypertension of unknown causes. Safety and effectiveness of the drug, a soluble guanylate cyclase stimulator, were established in clinical trials in which patients who used it for these conditions increased their 6-minute walk distance an average of 46 and 36 meters, respectively. The drug, which received priority review, carries a boxed warning about use in pregnant women. Common side effects included headache, dizziness, dyspepsia, peripheral edema, nausea, diarrhea and vomiting.

Macitentan (Opsumit) to treat pulmonary arterial hypertension . Safety and effectiveness of the drug, an endothelin-receptor blocker, were established in a long-term clinical trial (about 2 years on average) in which it was effective in delaying disease progression. It carries a boxed warning about use in pregnant women. Side effects included anemia, nasopharyngitis, sore throat, bronchitis, headache, flu and urinary tract infection.

Bedaquiline (Sirturo) as part of combination therapy to treat multidrug-resistant pulmonary tuberculosis when other alternatives are not available. The drug is being approved under the accelerated-approval, fast-track, priority-review and orphan-product programs. It carries a boxed warning about the risk of QT prolongation and deaths in patients on the drug (9 on the drug vs. 2 on placebo). Approval was based on trial results showing that patients on the drug achieved sputum culture conversion in a median of 83 days, compared with 125 days on placebo combination therapy. Common side effects included nausea, joint pain, and headache.

Obinutuzumab (Gazyva) for use in combination with chlorambucil to treat previously untreated chronic lymphocytic leukemia. Approval is based on a study of 356 participants in which patients on combination therapy had average progression-free survival of 23 months compared with 11.1 months with chlorambucil alone. The most common side effects were infusion-related reactions, neutropenia, thrombocytopenia, anemia, musculoskeletal pain and pyrexia. The drug carries a boxed warning about the risk of hepatitis B virus reactivation and progressive multifocal leukoencephalopathy.

Triamcinolone acetonide (Nasacort Allergy 24HR) for over-the-counter (OTC) treatment of nasal allergy symptoms (nasal congestion, runny nose, sneezing, and itchy nose). It is the first glucocorticoid made available OTC for treatment of nasal allergies. It is a nasal spray indicated for use once daily. There are different dosing instructions for adults and children 12 years of age and older, children 6 to under 12 years of age, and children 2 to under 6 years of age.

Flutemetamol F18 injection (Vizamyl), the second radioactive diagnostic drug approved for use with positron emission tomography (PET) imaging in evaluation for Alzheimer's disease (AD) and dementia. A negative scan means that there is little or no beta amyloid accumulation in the brain and the cause of the dementia is probably not due to AD. A positive scan means that there is probably a moderate or greater amount of amyloid in the brain, but it does not establish a diagnosis of AD or other dementia. The drug is not indicated to predict the development of AD or to check how patients respond to treatment, and PET images should be interpreted only by clinicians who successfully complete training in an image interpretation program.

Vortioxetine (Brintellix) to treat major depressive disorder (MDD). Approval was based on 6 trials in which adults with MDD randomly assigned to vortioxetine had better results than those on placebo and an additional study showing the drug decreased the likelihood of becoming depressed again after treatment of an MDD episode. The most common side effects included nausea, constipation and vomiting. It will be available in 5-mg, 10-mg, 15-mg and 20-mg tablets and will carry a boxed warning that antidepressants can increase the risk of suicidal thoughts and behavior in children, adolescents and young adults ages 18 to 24 during initial treatment.

A new indication for pertuzumab (Perjeta) as the first approved drug for neoadjuvant breast cancer treatment . The new indication covers patients with HER2-positive, locally advanced, inflammatory or early-stage breast cancer who are at high risk of death or having their cancer return or metastasize. It is to be used in combination with trastuzumab and other chemotherapy prior to surgery. In a randomized trial, about 39% of participants on pertuzumab plus trastuzumab and docetaxel achieved pathologic complete response, compared to about 21% on trastuzumab plus docetaxel. A confirmatory trial for this accelerated approval is expected to provide results in 2016. In 2012, pertuzumab was approved for the treatment of advanced or metastatic HER2-positive breast cancer.

A new indication for the Sapien Transcatheter Heart Valve (THV) to treat more patients with inoperable aortic valve stenosis. The FDA previously approved the valve for insertion through the femoral artery, the leg or the lower tip of the heart. The new labeling removes references to specific access points, making the device available for inoperable patients who need an alternate access point. Approval was based on data from the Transcatheter Valve Therapy Registry.