FDA turns down Hetlioz for jet lag once again

Vanda Pharma may have forced the FDA to revisit its marketing application for Hetlioz as a therapy for jet lag, but the outcome has remained the same.

Hetlioz (tasimelteon) has been approved in the US for a few years to treat sleep disorders affecting people who are blind or have the rare neurodevelopmental disorder Smith-Magenis syndrome (SMS), but an application to market it for jet lag was rejected by the FDA in 2019.

Earlier this year, a lawsuit filed by the company forced the regulator to reconsider its application, but that review has ended with a letter indicating it is unable to approve the drug for the potentially much larger jet lag indication.

In a statement, Vanda said the FDA had "acknowledged positive efficacy" in its clinical trials of Hetlioz in jet lag, but also concluded the data does not "provide substantial evidence of effectiveness."

Its objections stem from the view that the models for jet lag used in the studies – five- and eight-hour bedtime shifts – are not representative of the effects of long-distance plane travel, which also include factors like reduced oxygen pressure, physical constraints, noise, and lighting changes.

That sounds fairly definitive, but Vanda is undeterred, saying it "respectfully disagrees with this interpretation" and its trial protocols "induce the essential features of jet lag without the confounders of variable travel conditions, which are unrelated to jet lag."

The company also said that it does not believe the new rejection is in the spirit of a collaborative framework set up with the FDA to advance Hetlioz for this use after the courts concluded the agency should look at the data again.

"Vanda remains committed to working constructively with the FDA while pursuing all appropriate avenues to advance approval of Hetlioz for jet lag disorder and make this important therapy available to travellers," it added.

Melatonin receptor agonist Hetlioz contributed $18 million to Vanda's total revenues of $56 million in the third quarter of last year, with the remainder accounted for by fast-growing schizophrenia and bipolar I disorder therapy Fanapt (iloperidone) and Ponvory (ponesimod) for multiple sclerosis.

There was better news for Vanda at the end of last year, when the FDA approved Nereus (tradipitant) for the prevention of motion sickness, which analysts have suggested could contribute $100 million a year in US sales.

The company is also waiting for a decision from the regulator on Bysanti (milsaperidone), a follow-up therapy for schizophrenia and bipolar I, which is due by 21st February, while a filing for generalised pustular psoriasis (GPP) candidate imsidolimab took place last month.

Shares in Vanda fell more than 14% after the announcement.

Photo by Ross Parmly on Unsplash