Oral Suspension of Riluzole for ALS Receives FDA Approval

The US Food and Drug Administration (FDA) has approved Tiglutik, an oral suspension of riluzole for the treatment of amyotrophic lateral sclerosis (ALS). Tiglutik was created to be an easy-to-swallow, thickened liquid to ease administration for patients with ALS who develop dysphagia and have difficulty swallowing.

"Having a therapeutic option designed to specifically overcome the challenges of disease-related dysphagia in ALS is a welcome step forward for the many doctors, caregivers and people living with ALS who have relied on riluzole as the gold standard of treatment for more than 20 years to slow the progression of this devastating disease," said Hiroshi Mitsumoto, MD, DSc, Wesley J. Howe professor of neurology at Columbia University at The Neurological Institute of New York and New York-Presbyterian Hospital/Columbia University Medical Center, in a statement.

A dose of 50 mg oral suspension of riluzole is administered twice daily via an oral syringe. The Prescribing Information recommends administering Tiglutik at least 1 hour before or 2 hours after a meal.

"The availability of Tiglutik oral suspension precludes the need for manipulation of tablets by patients or caregivers, easing administration and may provide an opportunity for more accurate dosing and enhanced patient compliance," added Mitsumoto.

Two placebo-controlled trials of oral suspension riluzole included a total of 313 patients with amyotrophic lateral sclerosis. In Study 1 participants were randomized to receive 500 mg riluzole twice daily or placebo, while in Study 2 the arms were 100 mg riluzole twice daily or placebo.

In Study 1, 155 patients were followed for 13 to 18 months. The clinical outcome measure was time to tracheostomy or death. Time to tracheostomy or death was longer for participants in the riluzole treatment arm, and among participants who reached the endpoint of tracheostomy or death during the study, the difference in median survival was 90 days.

In Study 2, 959 patients were followed for 12 to 18 months, with the same outcome measure. Among patients who reached the endpoints, difference in median survival was 60 days.

For both studies the analysis specified in the study protocol did not find a significant difference between riluzole and placebo (Logrank test: Study 1 P = .076; Study 2 P = .12), but a Wilcoxon test did indicate statistical significance (Study 1 and 2 P = .05).

The most commonly reported adverse reactions (occurring ≥ 5% and greater than placebo) were oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain. For more details, refer to the full Prescribing Information for Tiglutik (riluzole).

"This is the seventh approval worldwide for Tiglutik and a very significant advance for ITF Pharma and Italfarmaco,” said Paolo Bettica, MD, PhD, vice president, research and development of Italfarmaco, the parent company of ITF Pharma. “We are pleased to bring this new therapeutic option to ALS patients in the United States."

Tiglutik was previously granted Orphan Drug designation and was approved under the FDA’s Fast-Track designation, which expedites the drug review process for products being developed to treat serious conditions and fill unmet medical needs.

In addition to the FDA approval, ITF Pharma announced that Tiglutik will be commercially available in the US by mid-October 2018. Tiglutik will be available in a 300 mL multiple-dose bottle.