NLS Pharmaceutics has recently announced new data confirming that its narcolepsy product, a controlled release (CR) formulation of mazindol, has agonist activity at orexin-2 receptors (OX2R). While mazindol is a monoamine reuptake inhibitor like the many other stimulants used to treat narcolepsy, the additional OX2R agonist activity could give it a competitive edge in the market, says GlobalData, a leading data and analytics company.

Philippa Salter, Neurology Analyst at GlobalData, comments: “There is a lack of disease-modifying or curative treatments for narcolepsy, with the currently available therapeutics providing symptomatic treatment only. Mazindol CR has the potential to become the first-available treatment for narcolepsy that targets the cause of the disease through agonist activity at the OX2R.

“However, mazindol CR will need to demonstrate strong efficacy in Phase III trials if it is to be competitive in the narcolepsy market as there are several factors which could limit its uptake. Not only is mazindol a scheduled IV controlled substance which will restrict its use, it has also been linked with several safety concerns.”

Some key opinion leaders previously interviewed by GlobalData indicated a reluctance to prescribe an immediate-release formulation of mazindol that used to be prescribed off-label to treat narcolepsy due to some safety concerns in terms of the sympathetic activity of mazindol, and also in terms of cardiac problems.

If NLS Pharmaceutics is successful in launching mazindol CR, it will face significant competition from several recently approved products, including Jazz Pharmaceuticals’ Sunosi (solriamfetol hydrochloride).

Salter adds: “Sunosi has experienced good uptake since its approval in US in 2019 and in the EU in 2020 as the most effective treatment available for improving excessive daytime sleepiness, a particularly challenging aspect of narcolepsy treatment. GlobalData forecasts that Sunosi will have global sales just shy of $300m by 2027. However, Sunosi has showed no evidence of efficacy in cataplexy so opportunities still remain in the narcolepsy market for safer, more effective therapies.”