The U.S. Food and Drug Administration (FDA) has approved the anti-epileptic drug Carnexiv (carbamazepine) injection for adults with certain seizure types, announced Lundbeck, the drug’s global pharmaceutical company.
The new indication of carbamazepine is as a replacement therapy in adults who are on a stable maintenance oral dose of carbamazepine (known by its brand names Tegretol, Carbatrol and Equetro when taken orally) and to control seizures when patients are temporarily unable to take the oral form of the drug.
The FDA granted Orphan Drug status to Carnexiv injection in 2013, and in April 2016, the agency accepted for review the company’s resubmission of a New Drug Application (NDA).
The therapy is expected to be available commercially in the U.S. early next year.
Carnexiv injection is a short-term treatment (seven days or less), administered by intravenous infusion every six hours. According to Denmark-based Lundbeck, the total daily dosage of Carnexiv should be 70 percent of the total oral dose of carbamazepine.
Carnexiv injection is to be used by adults who are diagnosed with generalized tonic-clonic seizures, partial seizures with complex symptomatology, and mixed seizure patterns. Patients should be switched back to their usual oral carbamazepine therapy as soon as clinically appropriate.
Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), as well as aplastic anemia and agranulocytosis, have occurred with Carnexiv and oral carbamazepine.
“Carbamazepine is very difficult to make as an aqueous-based injectable formulation, which means that doctors have not had an IV formulation of the drug available when needed,” James Cloyd, PharmD, director of the Center for Orphan Drug Research at the University of Minnesota College of Pharmacy, said in a press release.
“This approval is the result of years of work to create a novel and stable injection formulation to support patients who need an alternative to oral carbamazepine,” Cloyd said, adding that the center was proud to partner with Lundbeck and “appreciate the company’s dedication to overcoming development challenges” to make Carnexiv available for patients who need it.
Researchers recently reported tolerability findings and maintenance of seizure control with Carnexiv injection from a pooled analysis of Phase 1 open-label trial OV-1015 (NCT01079351) and Phase 3 trial 13181A (NCT01128959).
The data showed that multiple 15 or 30-minute infusions every six hours, and as a single rapid infusion, was well tolerated as a short-term replacement in 203 adults with epilepsy receiving stable doses of oral carbamazepine. Seizure control was generally unchanged when patients were switching between formulations, and infusion site reactions were the only adverse events reported.
Cloyd and his colleagues at the University of Minnesota partnered closely with Lundbeck during Carnevix’s development, proof-of-concept trials, orphan drug product and approval process.