The first tranche, of $610 million, will be paid following the EMA’s recommendation to approve cenobamate, which is expected at either the January or February meeting of the Committee for Medicinal Products for Human Use. The remaining $350 million is due when European sales of the oral therapy for treatment-resistant partial onset seizures reach $400 million.
The deal is “the most important investment” in the history of Rome, Italy-based Angelini, according to Thea Paola Angelini, executive vice president of the parent company, Angelini Holding. It will position the 100-year old business to extend the reach of its central nervous system and mental health disorders franchise across Europe. “This acquisition represents a milestone in our growth path, as it definitively drives us towards the multinational dimension,” she said.
This is a chunky return for Arvelle’s backers, who put $207.5 million into the series A when the company was established in 2019 to commercialize cenobamate in Europe. After paying Panyo, South Korea-based SK Biopharmaceuticals Co. Ltd., discoverer and developer of the drug, $100 million up front for the European rights, Arvelle has been investing the money in submitting the file to the EMA and laying the groundwork for commercialization.
SK is selling its 12% stake in Arvelle and will continue to be eligible for milestone payments and royalties on sales.
“An interesting aspect of the acquisition is that Angelini is building capabilities where it didn’t have [any],” said Mark Altmeyer, CEO and founder of Arvelle. “They will pick up on our momentum,” he told BioWorld.
On the back of the deal, Angelini said it plans to establish operations in France, the U.K., the five Nordic countries and Switzerland. That expansion will follow the setting up of a German subsidiary in April 2020.
In addition to cenobamate, Angelini’s CNS portfolio includes a prolonged release formulation of lithium sulphate for bipolar disorder and the patented antipsychotic drug Latuda (lurasidone,) to which owner Sumitomo Dainippon Pharma Co. Ltd. has granted Angelini European rights.
The offer to buy Arvelle came about as a result of an approach the company made to Angelini to discuss possible co-promotion of cenobamate. “Angelini has strengths in Italy, Spain and parts of central and eastern Europe, so the deal started around discussions about whether we could leverage their expertise,” Altmeyer said.
The series A was intended to fund Arvelle to mid-2021, and Altmeyer said there is plenty of cash to support it through the change of ownership. He will leave the company when the deal closes.
Cenobamate won FDA approval in November 2019 under the brand name Xcopri, with first prescriptions filled in May 2020, and has had a good start, according to Altmeyer. That gives grounds to be optimistic about the European prospects. “Despite significant headwinds launching in COVID, the product has done really well in the U.S.,” he said. “The unmet need is every bit as great in Europe.”
Although the precise mechanism of action is uncertain, cenobamate is thought to enhance inhibitory currents through positive modulation of GABA-A receptors, and to decrease excitatory currents by both inhibiting sodium currents and enhancing the inactivated state of voltage-gated sodium channels.
Around 60% of people with epilepsy suffer from focal seizures, located in just one part of the brain. Although there are a number of very effective generic drugs, some 40% of patients continue to have seizures after one or two lines of treatment.
In the clinical development program, the once-a-day tablet was tested in more than 2,500 subjects, including 1,900 patients. In one of two phase III studies, patients who received a 100-mg dose of cenobamate saw their seizure frequency decrease by a median of 35.5%, while in patients who received the 200-mg and 400-mg doses, seizure frequency decreased by a median of 55%. The median decrease among those who received placebo was 24%.
Notably, a number of patients who were resistant to other therapies saw reductions in seizure frequency of between 75% and 100%.
Longer-term safety and efficacy of cenobamate is being studied in open-label extension of the phase III trials.
In the U.K., cenobamate has been granted Promising Innovative Medicine status by the Medicines and Healthcare products Agency (MHRA). That opens the way to the Early Access to Medicines Scheme, which is intended to speed up patient access to drugs for life threatening or seriously debilitating conditions.
Although the U.K. is now firmly outside the EMA regulatory system, the MHRA will accept EMA decisions for the next two years. Altmeyer said there may be some additional bureaucracy, but the file submitted to the EMA should be sufficient for U.K. approval.