UCB's Keppra Follow-On Briviact Gains FDA Nod For Epileptic Seizures

FDA approval of UCB SA's Briviact (brivaracetam) gives the company a third anti-epileptic in its US portfolio and another opportunity to reduce reliance on sales from its mature seizure treatment Keppra.

FDA approved brivaracetam, a selective synaptic vesicle protein 2A ligand, as add-on treatment for partial onset seizures in patients ages 16 years and older with epilepsy.

The Feb. 18 approval came three months after the product's original estimated user fee goal date in November (Also see "December Approvals Forecast: FDA Decisions Will Be Fast And Frequent" - Pink Sheet, 25 Nov, 2015.).

UCB said the agency did not miss its user fee date and there was no complete response letter, but it could not comment further on agency timelines. It's possible that FDA extended the user fee goal date by three months.

The US launch must await controlled substance scheduling by the Drug Enforcement Administration, which the company said is anticipated within the next 90 days. The drug will be sold in film-coated tablets, oral solution and injection formulations.

UCB said it is finalizing pricing and will communicate that once the drug is commercially available.

Brivaracetam, a new molecular entity, is a next-generation version of Keppra (levetiracetam), a blockbuster agent that has faced increasing generic competition in US and foreign markets. Keppra is approved for adjunctive treatment of seizures in epilepsy patients 12 years and older.

UCB's epilepsy portfolio also includes Vimpat (lacosamide), which was first approved in October 2008 and is labeled for monotherapy or adjunctive therapy in patients with partial onset seizures.

Approximately 30% of people with epilepsy whose seizures remain uncontrolled on currently available therapies can experience devastating physical and emotional consequences as a result, UCB said. "We believe that Briviact may be an option for many of these patients."

“We are excited to introduce Briviact as a new therapeutic option that may make a difference in the lives of people with epilepsy in the US," Jeff Wren, UCB head of neurology and executive VP, said in a press release.

"This approval is the culmination of more than eight years of clinical trials involving more than 2,400 adult patients with partial-onset seizures. The development of Briviact builds upon our longstanding heritage in developing meaningful treatment solutions for people living with epilepsy,” Wren said.

Statistical Significance In 2 Of 3 Studies

The NDA included three Phase III trials that evaluated the efficacy and safety of adjunctive brivaracetam (ranging from 50 mg-200 mg/day) in patients with uncontrolled partial-onset seizures. The trials enrolled a total of 1,550 patients who were not adequately controlled with one to two concomitant anti-epileptic drugs.

Two of the studies had a primary efficacy outcome of percent reduction in seven-day partial-onset seizure frequency compared to placebo, but one of these trials failed to demonstrate statistical significance.

Consequently, UCB conducted the third study, which had a primary efficacy outcome of percent reduction in 28-day partial-onset seizure frequency over placebo (Also see "Epilepsy NMEs: A View Of The Playing Field" - Pink Sheet, 9 Jul, 2012.).

In the third study, both brivaracetam doses tested (100 and 200 mg/day) demonstrated statistically significant percent reductions in partial-onset seizure frequency per 28 days over placebo (25.2% and 25.7% for 100 and 200 mg/day, respectively).

Briviact labeling presents the primary efficacy results for all three studies.

Labeling also suggests that Briviact's efficacy is not optimized when used in conjunction with Keppra.

"In Studies 1 and 2, which evaluated Briviact dosages of 50 mg and 100 mg daily, approximately 20% of the patients were on concomitant levetiracetam. Although the numbers of patients were limited, Briviact provided no added benefit when it was added to levetiracetam," labeling states.

"Although patients on concomitant levetiracetam were excluded from Study 3, which evaluated 100 and 200 mg daily, approximately 54% of patients in this study had prior exposure to levetiracetam."

The most common side effects reported in the Phase III controlled trials were somnolence and sedation, dizziness, fatigue, and nausea and vomiting.

Briviact must be dispensed with a Medication Guide on the drug's risks. "As is true for all drugs that treat epilepsy, the most serious risks include thoughts about suicide, attempts to commit suicide, feelings of agitation, new or worsening depression, aggression and panic attacks," FDA said in a press release.

Relying Less On Keppra

Briviact's approval should aid UCB's strategy of reducing its reliance on Keppra sales.

In 2012, revenues from three major newer products – the tumor necrosis factor inhibitor Cimzia (certolizumab), Vimpat and the Parkinson’s therapy Neupro (rotigotine) – combined to overtake Keppra sales (Also see "UCB Exercises Tozadenant Option But Asks Biotie To Move It To Phase III" - Pink Sheet, 27 Feb, 2013.).

During the first half of 2015, Cimzia, Vimpat and Neupro sales totaled €942m ($1,034m), accounting for 55% of the company's total net sales, while Keppra brought in revenues of €385m (Also see "UCB Buoyed By Strong First-Half, Lupus Ambitions Undented" - Pink Sheet, 31 Jul, 2015.).

In January, Briviact received European Commission marketing authorization following a positive opinion two months earlier from the European Medicines Agency's Committee for Medicinal Products for Human Use. UCB also has regulatory submissions pending in Australia, Brazil, Canada, Russia, Switzerland and Turkey.

UCB has its eyes set on further expansion in the epilepsy therapeutic category.

A Phase III program for Vimpat as adjunctive therapy in primary generalized tonic-clonic seizures is underway. The drug also is in Phase III for pediatric adjunctive therapy in epilepsy, according to UCB's pipeline.

Results are expected in the fourth quarter from a Phase II trial of UCB0942, a pre- and post-synaptic inhibitor, in patients with highly drug resistant focal epilepsy.

UCB said that while FDA's approval of Briviact did not include any post-marketing safety surveillance requirements, "we are committed to continuing to evaluate the safety and effectiveness of Briviact in a number of different patient populations who may benefit … including children living with epilepsy."