Alkermes breaks new ground in narcolepsy with orexin drug

Alkermes' alixorexton has become the first drug in the orexin 2 receptor agonist class to show efficacy in phase 2 trials involving patients with both main subtypes of sleep disorder narcolepsy.

Topline data from the dose-ranging Vibrance-2 study in patients with narcolepsy type 2 (NT2) – which causes excessive daytime sleepiness without sudden loss of muscle tone (cataplexy) – will support a phase 3 programme for alixorexton (formerly ALKS 2680), according to the Ireland-domiciled drugmaker.

The encouraging clinical data with alixorexton come just a few weeks after Alexion reached an agreement to buy Avadel Pharma and its already-approved narcolepsy therapy Lumryz (sodium oxybate) for up to $2.1 billion, part of a strategic push by the company into the sleep disorder category.

In Vibrance-2, alixorexton met both of the study's primary endpoints, showing statistically significant improvements in wakefulness and excessive daytime sleepiness compared to placebo, and according to Alexion was "generally well tolerated" at all tested doses (10, 14, and 18 mg once-daily).

There was a significant improvement in the Maintenance of Wakefulness Test (MWT) scale at the 14 mg and 18 mg doses, and for the 18 mg dose alone on the Epworth Sleepiness Scale (ESS).

However, Alexion maintains that all doses achieved "clinically meaningful" improvements on both efficacy measures. The most common side effects were an increased urge to urinate, insomnia, dizziness, and headache.

Alixorexton is in a race to what has been predicted to be a multibillion-dollar market with Takeda's rival, twice-daily drug in the orexin 2 receptor agonist class, oveporexton. Takeda already has phase 3 data in hand and is being prepared for filing this fiscal year for narcolepsy type 1 (NT1), whose symptoms also include cataplexy.

Alkermes already has positive results for alixorexton in NT1 from the phase 2 Vibrance-1, while Takeda is developing another drug in the class – TAK-360 – for the NT2 indication. Both types are rare, with NT1 affecting one in 3,000 to 5,000 people and NT2 seen in around one in 4,000.

A phase 3 programme for alixorexton in NT1 and NT2 will start next year, according to Alkermes.

It is testing the drug in another sleep disorder, idiopathic hypersomnia (IH), in the phase 2 Vibrance-3 trial, and also hopes to extend the label for Lumryz to include IH, which affects tens of thousands of patients in the US alone.

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