Vyglxia (troriluzole)

Spinocerebellar ataxia (SCA) is an inherited disease in which nerve cells in the cerebellum, the part of the brain that controls balance and coordination, slowly die over time. As those cells are lost, people gradually lose the ability to walk steadily, use their hands, and speak clearly.

Scientists believe one reason those cells die is because they are flooded by too much of a brain chemical called glutamate, which is helpful in normal amounts but toxic in excess. Troriluzole is designed to reduce that toxic buildup. It is a modified version of an older drug called riluzole, which has been approved for ALS since 1995.

After you swallow the capsule, your body converts troriluzole into riluzole, which helps nerve cells mop up the extra glutamate. In the Phase 3 study it was taken once a day^[6], while the original riluzole tablets are taken twice a day.

In the 48-week placebo-controlled part of the Phase 3 study, the most common side effects in people taking troriluzole were headache (12%, against 7% on placebo), tiredness (9% against 8%) and nausea (6% against 1%). Dizziness was reported slightly less often on troriluzole than on placebo (8% against 10%)^[6].

The older riluzole tablets can raise liver enzyme levels and require regular blood tests to watch the liver. More complete safety information will come from the FDA label if the drug is eventually approved.

Biohaven's Phase 3 study (Study 206) began with a 48-week placebo-controlled phase in 218 people. It missed its main goal, the change on the f-SARA scale at week 48^[6]. Biohaven then compared people who stayed on troriluzole for 3 years in the open-label extension with untreated SCA patients from separate natural history studies. In that comparison, Biohaven reports, people taking troriluzole got worse about 50% to 70% more slowly^[2][3].

In the placebo-controlled phase, falls were reported in 12% of people on troriluzole against 22% on placebo (13 of 108 and 24 of 109)^[6]. The 3-year comparison met the main goal Biohaven set for it, a slower rise in score on the f-SARA scale, a standard doctor-rated measure of balance, walking, hand use, and speech. When the FDA turned down the drug in November 2025, it did not say the drug doesn't work.

Instead, it said the study design, comparing trial patients to a separate database rather than to patients taking a placebo in the same trial, had weaknesses that made it hard to be sure how much of the benefit was actually from the drug. The FDA's letter pointed to possible bias, design flaws, a lack of pre-specified analyses and unmeasured factors in the external comparison^[5][4].

Biohaven created troriluzole as an improved version of riluzole, which has been on the market for ALS since 1995. Riluzole works but has some drawbacks, it has to be taken twice a day, meals can interfere with absorption, and it can raise liver enzyme levels, which means doctors need to order regular blood tests.

Troriluzole was designed as a once-a-day alternative. Biohaven ran Phase 2 and Phase 3 studies in SCA patients, got an 'orphan drug' designation from the FDA (a special status for rare-disease treatments), and filed for approval under the brand name VYGLXIA.

The FDA gave the application a faster 'Priority Review'^[8] but on November 4, 2025 turned it down with a Complete Response Letter that questioned the study's external comparison^[2]. After the rejection, Biohaven announced plans to cut its research spending by about 60% while it works on a response to the FDA^[9]. In November 2025 Biohaven said it was formally requesting a meeting with the FDA^[2], and Fierce Biotech later reported its CEO saying the company was in an appeal process. Neither Biohaven nor the FDA has said publicly whether that meeting took place or what came of it, and troriluzole no longer appears on Biohaven's online pipeline page. Troriluzole remains available through an expanded access program (NCT06034886). In Europe, Biohaven withdrew its application for the brand Dazluma on March 24, 2025. The EMA's provisional view was that the drug could not have been approved, because the main study did not show it worked better than placebo and the drug had not been shown to be a new active substance distinct from riluzole. Biohaven says it plans to generate more data and apply again^[7].