Dr Michael Thorpy Discusses Pharmacological Pathways for Idiopathic Hypersomnia

Despite the condition of idiopathic hypersomnia being around for quite some time, the first FDA approval for a drug to treat it was not until 2021, said Michael Thorpy, MD, professor of neurology, Albert Einstein College of Medicine.

The latest research in sleep disorder treatment was presented at the 2024 SLEEP: American Academy of Sleep Medicine and Sleep Research Society (APSS) Annual Meeting.

Transcript

What are the most promising pharmacological treatments currently being developed for hypersomnia, and how do they differ from existing therapies?

For the condition [of] idiopathic hypersomnia, we've had very few medications available to us. Most of the medications that we've used up to now have been used off label. The medications that have been developed for narcolepsy and have been applied to idiopathic hypersomnia, but there are a few that have been used off label for quite some time. One is clarithromycin, and that's now undergoing further investigation in phase 2 studies. This is actually an antibiotic, but it has effects that are quite significant in terms of improving daytime sleepiness.

The other medication that is available is called oxybate, [which] was approved in 2021 for the treatment of idiopathic hypersomnia. There is one form of it called low-sodium oxybate, which is given twice at night, and that that has proven to be the most effective agent for idiopathic hypersomnia. It's the only one that's FDA approved.

But there are some more recent medications that are undergoing study for idiopathic hypersomnia. There's one called serdexmethylphenidate, which is a variation of methylphenidate. The common form of that is Ritalin. We know that's an alerting agent, but has been developed as a longer acting form of it that's given before sleep at night. The patients are able to sleep through the night with this medication, [it] helps them wake up in the morning, and deals with the daytime sleepiness.

There's another medication that's approved for narcolepsy called pitolisant, and this is now being studied for idiopathic hypersomnia. It works by a different mechanism altogether than the others, and it's very effective for cataplexy, sleepiness, and narcolepsy. But because it's effective for the sleepiness in narcolepsy, it's now being applied to idiopathic hypersomnia. So, we're just doing phase 3 studies at the moment with this drug called pitolisant.

There is also a different form of oxybate that's available, it's called once-nightly oxybate. It's given only once before sleep at night. And again, this has been effective for the treatment of narcolepsy, but now is being studied for the treatment of idiopathic hypersomnia.

And finally, there's a new class of drugs called orexin agonists, and these are being studied mainly in narcolepsy, but one of the companies is studying the same medication, or a form of the medication, in idiopathic hypersomnia. So, we have quite a few different types of medications that are being applied and are currently being studied for the treatment of this condition which has been around for such a long time. But there's never been an FDA-approved treatment for it until the low-sodium oxybate was approved in 2021.