Jazz Pharmaceuticals is pausing its phase 1 clinical trial investigating JZP441, an oral orexin-2 receptor agonist with potential application for the treatment of narcolepsy and other sleep disorders, after reports of adverse effects.

Jazz’s senior vice president and chief medical officer Kelvin Tan, MB BCh, MRCPCH, said during the 6th annual Evercore ISI HealthCONx Conference on Tuesday that the study achieved proof of concept in healthy volunteers based on the maintenance of wakefulness test but is being paused due to “emerging information” on reports of visual disturbances and cardiovascular effects in study participants that the company is “seeking to understand and characterize much further.” 

“I remind you that orexin programs in general are very much in the early stage, and that’s across the board…So we will be providing further updates. Don’t expect anything too soon as we continue to understand fully and characterize these emerging data that we’re seeing for JZP441,” Tan said during the conference.  

Orexin agonists remain a focus for Jazz, according to Tan, who noted that the company has a backup program in orexin agonists with “a range of molecules.”

“I think, as you know, this field is emerging, of course, in its early days,” said Philip Jochelson, MD, vice president of therapeutic area head, sleep and CNS, during the conference. “We’re seeing a lot of data at World Sleep that would suggest that half-life is going to be important. Therapeutic index with regard to on-target toxicity or on-target effects versus off-target effects is also going to be important. So I think we just want to further characterize this.”

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Jazz acquired development and commercialization rights for JZP441 in specific markets from Sumitomo Pharma Co Ltd last year. Sumitomo had initiated a phase 1 trial in Japan to evaluate the drug’s safety, tolerability, and pharmacokinetics in healthy volunteers in November 2021, and Jazz expressed its intention to expedite the drug’s development based on the clinical findings.

Renee Gala, executive vice president and CFO of Jazz, stressed during the conference that the JZP441 program is not being terminated. 

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