Court sides with Vanda over FDA's Hetlioz rejection

Six years ago, the FDA turned down an application by Vanda Pharma seeking approval to sell its sleep disorder therapy Hetlioz for jet lag. Now, it has won an appeals court judgment forcing the agency to think again.

Washington DC-based Vanda was sent a complete response letter (CRL) from the FDA in 2019, rejecting Hetlioz (tasimelteon) for 'jet lag disorder' (JLD) on the grounds that the trials used to support the filing were of "unclear clinical significance."

Hetlioz has been approved in the US since 2014 as the first treatment for blind people who are experiencing a disrupted body clock and irregular sleep patterns, and had its label extended in 2020 to include nighttime sleep disturbances in the rare neurodevelopmental disorder Smith-Magenis syndrome (SMS).

Sales in those rare conditions have been modest, currently running at around $20 million a quarter, although it has started to feel the impact of generic competition. Vanda had been hoping for quite a lot of upside if Hetlioz could have tapped into usage by people taking long-haul flights, and also had method-of-use patents covering JLD awarded in the US as recently as 2024.

The company has accused the FDA of "substantially delaying" its request for a hearing to discuss its marketing application and – when forced to do so by a district court – summarily issued the CRL and disregarded the "voluminous factual evidence" submitted in support of the JLD indication.

Now, after an appeal, a judge has concluded that Vanda had "clearly offered meaningful evidence of tasimelteon's efficacy in improving sleep disturbance" and ordered the FDA to reconsider the application. According to Vanda, that will likely either mean it will approve the application or grant its request for a hearing.

In the small JET study originally submitted in support of the filing, which included 25 subjects, those taking Hetlioz reported sleeping nearly three hours longer over the three nights following their transatlantic trip when treated with Hetlioz than they did over the three nights following their untreated transatlantic trip. That was consistent with jet lag simulation studies, according to the company.

The results is good news for Vanda's efforts to broaden Hetlioz label, but also "significantly alters the relationship between the FDA and the parties it regulates" as it sets a precedent that suggests the regulator must engage with the evidence presented by drug innovators, and may not shield its decisions via a 'plea for deference' – essentially kicking a decision down the road.

Photo by Kevin Andre on Unsplash