Sleep Disorders, Circadian Rhythm

Vanda's Fanapt was originally approved by the FDA in 2009 as a treatment for schizophrenia. Fifteen years after gaining its first FDA approval for Fanapt (iloperidone) to treat schizophrenia, Vanda Pharmaceuticals has scored again with the same antipsychotic drug. The FDA has signed off on Fanapt tablets to treat adults with manic or mixed episodes associated with bipolar I disorder. Those with manic or mixed episodes are a subset of the 10 million in the U.S. with bipolar I, which is characterized by mood swings from euphoria to depression. The approval “significantly increases the commercial opportunity for Fanapt," Vanda said in a release. Investors agreed as Vanda’s share price increased by 40% on Wednesday morning. The boost is much needed for the Washington, D.C.-based company which has seen revenue fall from a record high of $269 million in 2021 to $193 million last year. Iloperidone has a long history dating to the mid-1990s, with Novartis and Titan Pharmaceuticals taking turns developing it before Vanda acquired it in 2004. After rejecting iloperidone in 2008 because of a lack of clinical data, the FDA approved it in 2009. Upon its launch, Jefferies analysts estimated sales would reach $300 million by 2013. But Fanapt never met those expectations. Over the next decade, sales increased slowly, peaking at $95 million in 2021. Last year, Fanapt generated $90 million in revenue. Vanda’s revenue slide over the last two years is attributed largely to declining sales of its other major product Hetlioz (tasimelteon), a treatment for the circadian rhythm disorder Non-24. Generic competition in the U.S. has caused Hetlioz sales to tumble from $160 million in 2022 to $100 million last year. Over the years, Vanda has been unsuccessful in its bid to gain approvals for Hetlioz to treat insomnia and jet lag disorder. The company is hoping to fill the revenue void by spending $100 million to secure rights in the U.S. and Canada to Johnson & Johnson's multiple sclerosis treatment Ponvory. Vanda made the deal in December of last year. The FDA based its latest approval of Fanapt on results from a phase 3 trial of 400 patients. Those on Fanapt showed improvements on the Young Mania Rating Scale over four weeks compared to those on placebo. Evidence of improvement was seen as early as two weeks of being on the medication. Fanapt comes with a boxed warning about an increased risk of death for elderly patients with dementia-related psychosis who are treated with antipsychotic drugs. Vanda is also investigating Fanapt as a treatment for post-traumatic stress disorder (PTSD).

The FDA cleared Vanda Pharmaceuticals’ Fanapt (iloperidone) for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults, marking the oral atypical antipsychotic’s second US approval following authorisation for schizophrenia in 2009."Manic or mixed episodes associated with bipolar I disorder are highly complex conditions, which require a host of trusted options to meet individual patient needs,” said Vanda CEO Mihael Polymeropoulos, adding that Fanapt is a “therapeutic agent that offers flexible dosing with a well-known safety profile.”  The expanded label approval was based on findings from a Phase III study, in which 400 participants with bipolar I disorder experiencing a current episode of mania were randomly assigned to either Fanapt or placebo. At the four-week assessment, Fanapt demonstrated a significantly greater improvement than placebo on the primary endpoint of mania severity, as measured by the Young Mania Rating Scale (YMRS). Moreover, clinical benefits were evident in the Fanapt group as early as week two.Vanda noted that Fanapt’s safety profile was consistent with its previous studies in schizophrenia. The drug’s label carries a boxed warning highlighting an increased risk of death in elderly patients with dementia-related psychosis.Within its neuropsychiatric portfolio, Vanda is also looking to broaden the label for Hetlioz (tasimelteon), which was approved for non-24-hour sleep-wake disorder in 2014 and nighttime sleep disturbances associated with Smith-Magenis Syndrome in 2020. However, the melatonin receptor agonist was slapped with a complete response letter by the FDA for its label expansion in jet lag disorder in 2019 and more recently in insomnia.

The FDA on Tuesday turned down Vanda Pharmaceuticals’ request for a hearing on issues the agency found with the company’s application for a jet lag indication for its sleep disorder drug Hetlioz, another blow to the company and its strained relationship with the agency. The FDA’s decision nixes chances that Vanda’s Hetlioz, which is approved for other sleep disorders, will be granted an indication for jet lag disorder. The FDA cited issues with the endpoints used in the trials, said there was no debate about the facts and data for the drug, and that it wasn’t in the public interest to reconsider.