AAN 2024: Troriluzole may be taken with food, data suggest
3 single-center studies tested treatment in healthy volunteers
Troriluzole, a new formulation of the approved amyotrophic lateral sclerosis (ALS) treatment riluzole, can be taken with or without food and appears to have better pharmacological properties than approved versions of the medication that allow once daily administration.
That’s according to data from three studies in healthy volunteers presented by Heather Sevinsky, executive director of clinical pharmacology and pharmacometrics at Biohaven Pharmaceuticals, which is developing troriluzole.
Sevinsky’s talk, “Next Generation Prodrug Troriluzole: Increased Bioavailability of Riluzole with No Food Effect in Healthy Subjects,” took place at the American Academy of Neurology (AAN) 2024 Annual Meeting held April 13-18 in Denver, Colorado, and online.
Riluzole was approved in the 1990s as the first treatment for ALS. An oral therapy thought to reduce nerve damage by altering neurological signaling, it was originally authorized under the brand name Rilutek, which is sold as tablets. Other formulations taken as an oral suspension (Tiglutik) or an oral film (Exservan) have also been approved in more recent years.
Although riluzole has been proven to slow the progression of ALS, the therapy has some notable drawbacks. It can cause liver damage, requires twice daily administration, and has to be taken on an empty stomach because food can prevent the medication from being absorbed properly.
Aim is safer, easier formulation
Troriluzole is a prodrug, an inactive agent that is converted into therapeutic riluzole once inside the body. Biohaven is developing the therapy with the goal of creating a new riluzole formulation that’s safer and easier to take.
“Trorilulozole is a novel prodrug that was designed to overcome the shortcomings of oral riluzole,” Sevinsky said.
Biohaven has conducted three, single-center studies to test the safety and pharmacological effects of a single dose of troriluzole in healthy volunteers.
The first study, which involved 24 participants, compared the bioavailability of troriluzole, at a dose of 100 or 280 mg, against that of oral riluzole at the approved dose of 50 mg. Bioavailability refers to how much of the drug is absorbed into the body.
Results showed that the maximum concentration of active riluzole in the bloodstream was similar for oral riluzole compared with any of the troriluzole doses tested. However, levels stayed higher for longer with troriluzole, such that the total amount of active riluzole in the blood over time was 40% to 50% higher with troriluzole.
Sevinsky noted that troriluzole also led to markedly less variability in levels of riluzole in the bloodstream. Levels varied by about 40% with troriluzole, compared with more than 50% with oral riluzole.
The other two studies, which collectively involved 26 volunteers, tested whether taking troriluzole with food alters how the body absorbs the drug.
Results indicated that, when the 280 mg dose of troriluzole was taken with a fatty meal, the time it took for blood riluzole levels to reach a peak was delayed by about two hours, and the maximum concentration was 20% lower compared with taking the therapy on an empty stomach.
Nonetheless, when considering the total amount of the medication in the bloodstream over time, “the overall riluzole absorption … was unaffected by food,” Sevinsky said.
To put those results in perspective, Sevinsky said that when oral riluzole is taken with a fatty meal, the total amount of drug in the bloodstream over time is reduced by about 20%.
Collectively, these three studies “confirm higher bioavailability of riluzole when administered as troriluzole and demonstrate troriluzole may be taken without regard to food,” Sevinsky said.
“Additionally, results show lower variability of riluzole, representing an optimized profile allowing once daily administration,” she added, noting that the findings support further development of the new treatment formulation.
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