An employee at Xenon works inside the lab in Burnaby, B.C, in December, 2023.Tijana Martin/The Globe and Mail
Rick Bishop got a black Labrador named Sailor in 2017 to help deal with the epileptic seizures he had multiple times daily. Sailor hasn’t had much to do since the rural Pennsylvania-based retiree started taking an experimental drug made by Burnaby, B.C.-based Xenon Pharmaceuticals Inc. XENE-Q
Mr. Bishop has been seizure-free since the early 2020s, dating to when he went on the drug, called azetukalner, as part of a 325-adult trial of epilepsy patients who had little luck with other medications. It’s a marked change for someone who has participated in trials of multiple drugs, one of which impaired his vision. Taking azetukalner has led to a “100-per-cent improvement,” in his quality of life, he said in an interview.
Results from that study published in 2021 showed participants with the most common form of epilepsy (focal onset seizures) who took azetukalner saw median seizure activity drop by more than half after six months. In follow-up studies, 25 per cent of participants who kept using the drug were seizure-free over any subsequent 24-month period; 10.7 per cent of them had no seizures at all.
Those results vaulted Xenon to become Canada’s most valuable publicly traded drug developer. Now, the company is set to publish data that could further jolt the stock and enable it to take the drug to market.
Xenon is set to release results from a late-stage trial of 380 patients in the first half of March. If that study mirrors the success of the 2021 trial, Xenon expects to file for approval by the U.S. Food and Drug Administration this year to sell the drug in the United States, where three million people have epilepsy.
Rick Bishop and his black Labrador Sailor.Supplied
Several analysts who follow Xenon are optimistic azetukalner will again deliver a statistically significant improvement over placebo results and 50-per-cent-plus seizure reduction. “There is a high probability that this trial will succeed, and the drug will get approved,” said Bloom Burton analyst David Martin in Toronto.
If so, azetukalner would be the 15th therapy developed in B.C. to win regulatory approval, according to the industry association Life Sciences B.C. That includes innovations from pioneers QLT and Angiotech, plus an antibody discovered in 2020 by AbCellera Biologics Inc. used to treat COVID-19 patients. Acuitas Therapeutics developed the lipid nanoparticle that delivered the Pfizer-BioNTech COVID-19 vaccine in patients.
Xenon’s drug modulates the flow of potassium ions through electrical channels in the nervous system, tempering excessive brain activity that causes seizures. Other epilepsy drugs typically focus on sodium channels.
People in the Xenon study are among the most treatment-resistant epilepsy patients and typically take multiple anti-seizure drugs already, said Dr. Jacqueline French, a New York University neurology professor who helped conduct the trial. They were split into three groups for the latest study: participants either took a daily 15-mg pill, a 25-mg pill or a placebo. All were monitored for more than two months to determine baseline seizure activity before starting the 12-week study.
The drug, Jefferies analyst Andrew Tsai said in a recent note, has already “produced one of the most compelling pivotal datasets in focal epilepsy.” He expects it to become a US$1-billion-plus per year seller and said doctors have “consistently endorsed azetukalner as a potential best-in-class epilepsy drug.”
2023: B.C. biotech boom: Vancouver looks to join the global big leagues of modern medicine
The reason doctors like it, said Dr. French, is that “it’s easy, safe and fast.” Unlike other anti-seizure drugs, it doesn’t require a gradual increase in dosing over weeks. Xenon is running additional studies to see if azetukalner alleviates mood disorders and pain.
Xenon, which has a market capitalization of US$3.5-billion, has raised US$1.4-billion to date but would need more to take azetukalner to market, chief executive officer Ian Mortimer said in an interview. That could mean having another equity raise, striking a distribution partnership or selling out to Big Pharma.
The company, co-founded by University of British Columbia geneticist Michael Hayden and postdoctoral student Simon Pimstone in 1996, started in gene discovery but shifted focus to drugs affecting sodium channels that played a key role in signalling pain. Xenon went public in 2014 and partnered with drug giants to develop pain treatments, but those programs failed or fizzled out. In March, 2017, Xenon’s stock plummeted when its acne drug failed efficacy trials.
But its work led to exploration of neurological conditions Xenon could treat, including epilepsy. That resulted in a partnership with another Canadian company.
Xenon CEO Ian Mortimer says the company has raised US$1.4-billion but would need more to take azetukalner to market.Tijana Martin/The Globe and Mail
Valeant Pharmaceuticals International (now renamed Bausch Health Companies) had developed a potassium channel-modulating drug called ezogabine to treat epilepsy. While it reduced seizures markedly, ezogabine required a gradual buildup of dose strength and had to be taken three times a day, causing side effects that included fatigue and dizziness. It also turned patients’ skin blue.
That drug, marketed by GSK plc, was approved in 2011 but regulators ordered that it carry warnings about the discoloration and threat of vision changes. GSK discontinued it in 2017, blaming limited sales.
Valeant knew ezogabine had problems and looked for alternatives using a similar approach but different chemistry. It devised a potassium ion channel drug that wouldn’t require graduated dosing and could be taken once daily at night, minimizing the impact of side effects. It didn’t turn anyone blue.
As Valeant encountered market challenges in 2015, an ex-company researcher set out to rescue the unproven drug. Valeant licensed it to him in 2015 and Xenon later acquired all rights to azetukalner from the researcher and Valeant.
“A biotechnology company’s journey is long and incredibly challenging,” Mr. Mortimer said. “There are many setbacks along the way, but we are on the doorstep of what all companies want to do.”
Mr. Bishop, the retiree, is eager to see azetukalner succeed even though it causes side effects such as sleepiness and dizziness, and for him, tremors and occasional incontinence.
But he hasn’t paid for the drug as a study participant and it’s likely to cost US$15,000-plus annually per patient, said Needham & Co. analyst Serge Belanger. Mr. Bishop’s medical bills have wiped out his retirement savings already. “I won’t even know how to afford it,” he said.