Pharmaceutical treatment for different types of epilepsy generally still relies on tried-and-true generics, despite recent efforts by drug manufacturers to introduce new branded medications into the mix, PBM insiders say.
Xcopri (cenobamate tablets) launched in May for the treatment of partial-onset seizures in adults. According to manufacturer SK Life Science, Inc., a subsidiary of SK Biopharmaceuticals Co., Ltd., clinical trials have shown “significant reductions in seizure frequency compared to placebo at all doses studied, and as many as one in five patients achieved zero seizures during the maintenance phase.”
However, multiple plans haven’t jumped to add Xcopri — which carries an average price of around $1,200 for a 30-day supply — to their formularies, says Mesfin Tegenu, R.Ph., president of PerformRx.
“Some plans have opted to take a cautious approach and leave the medication as non-formulary to start,” Tegenu says. “It is difficult to tell the impact of this new drug launch on the treatment of epilepsy. However, Xcopri trials demonstrated high efficacy in partial onset seizures and refractory epilepsy, lending it a strong clinical profile. One could reasonably suspect a high impact on the epilepsy treatment paradigm.”
In most cases, though, generics are the first-line treatments for many forms of the disorder, according to Tegenu. Many of the drugs used to treat epilepsy are covered without restriction by plans, Tegenu says, adding, “there are also a handful of newer branded agents which may be formulary-restricted.”
Utilization management is uncommon on the generic products used to treat epilepsy, he says, while “on some of the newer, more expensive brand products, prior authorization can be used.”
April Kunze, senior director of clinical formulary development and trend management strategy for Prime Therapeutics LLC, tells AIS Health that she sees a rationale for using newer branded products in some circumstances: “Newer products may offer additional treatment options, as it often takes more than one therapy to effectively treat patients with seizures. In general, Prime management strategies aim to focus on appropriate use of products.” Generics are widely used in epilepsy treatment “as they have the long-term safety and efficacy data,” she adds.
Some PBMs Apply Quantity Limits
Prime Therapeutics treats Xcopri as a non-preferred brand, Kunze says. Premera Blue Cross’ Medicare Advantage (MA) formularies, Cigna’s national preferred formulary and HealthPartners’ commercial formularies impose quantity limits on Xcopri, according to their plan documents. Xcopri is covered on tiers 4 and 5 on Florida Blue’s two MA formularies.
Epilepsy treatment relies on a wide variety of drugs; the Epilepsy Foundation lists more than three dozen different medications used to treat various forms of the disorder, which can manifest in seizures that begin in childhood or adulthood.
Common anti-epileptic drugs include valproic acid, carbamazepine, lamotrigine, levetiracetam and topiramate. Most of these medications also have other indications — valproic acid, carbamazepine and lamotrigine can be used to treat bipolar disorder, for example, while topiramate is indicated for migraine treatment.
Still, some cases of epilepsy are resistant to treatment with common medications. “There are still various areas of unmet need in the epilepsy market, particularly in refractory cases and the rare epilepsies,” Tegenu says.
In November 2018, GW Pharmaceuticals launched its product Epidiolex (cannabidiol), a much-anticipated new drug for two rare forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. It’s the first and only cannabidiol-derived medication to be approved by the FDA.
In August, the FDA expanded indications for Epidiolex to include seizures associated with tuberous sclerosis complex (TSC) in patients age 1 or older, and it also expanded the age range for eligible patients with Lennox-Gastaut syndrome and Dravet syndrome. Both are severe forms of childhood-onset epilepsy that are difficult to treat.
Is Epidiolex Worth the Price?
“Based on previous positive trial results in TSC patients, Epidiolex may become an important treatment option for patients,” Elizabeth Thiele, M.D., Ph.D., director of the Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital, said in a statement when the FDA widened Epidiolex indications. “Nearly two-thirds of individuals with TSC develop treatment-resistant epilepsy and there is a need for new options that may benefit these patients who often try and fail existing treatments.”
Epidiolex’s list price is $32,500, a price tag that raised some eyebrows in the wider medical cannabis community at the time of the drug’s launch.
GW Pharmaceuticals said in August that it expected “most payers will quickly update their Epidiolex coverage policies to include TSC at access levels similar to that of LGS [Lennox-Gastaut syndrome] and Dravet syndrome.” Epidiolex is a preferred brand for Prime Therapeutics, Kunze says. Other plans, including Rocky Mountain Health Plans, require prior authorization for Epidiolex, according to plan documents.
For his part, Tegenu expresses some skepticism about the drug. “Epidiolex represents another option for treatment of Lennox-Gastaut and Dravet syndrome,”
Tegenu says. “However, its efficacy hasn’t shown significant improvement relative to existing treatments.”
Meanwhile, Zogenix, Inc.’s Fintepla (fenfluramine), a Schedule IV controlled substance, also was approved recently for Dravet syndrome after it demonstrated “significantly improved efficacy,” but its impact “remains to be seen as the drug was only recently launched in July 2020,” Tegenu said.
Fintepla is a lower dose of the appetite suppressant fenfluramine, half of the infamous Fen-Phen weight loss product that was discontinued after having been linked to heart valve damage in the 1990s. Although clinical trials of Fintepla didn’t show similar damage, a small minority of patients had abnormal echocardiograms, and the FDA therefore requires patients to receive an echocardiogram prior to treatment.
Although multiple pharmaceutical manufacturers are researching new medications for various forms of epilepsy, there’s not much on the horizon for the immediate future, Tegenu says. “In the near-term pipeline — one year outlook — there are a handful of drugs pursuing indications for epilepsy, but they are all reformulations of older molecules.”
by Jane Anderson