The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for JZP-258 (Jazz Pharmaceuticals) for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients aged ≥7 years with narcolepsy.
JZP-258 is an investigational novel oxybate product that is believed to work by modulating GABAB during sleep. It contains the same oxybate concentration as Xyrem® (sodium oxybate; Jazz Pharmaceuticals) but with 92%, or approximately 1000 to 1500 milligrams, less sodium.
The application is supported by data from a multicenter, double-blind, placebo-controlled, randomized-withdrawal, phase 3 study that evaluated the efficacy and safety of JZP-258 in the treatment of cataplexy and EDS in 134 adults with narcolepsy. The study included a titration period of up to 12 weeks, a JZP-258 stable-dose period of 2 weeks, followed by a double-blind randomized-withdrawal period in which patients were randomized 1:1 to either JZP-258 or placebo for 2 weeks. The primary end point was the change in the number of cataplexy attacks; a secondary end point included the change in Epworth Sleepiness Scale (ESS) score (rated from 0 [would never doze] to 3 [high chance of dozing]).
Findings from the double-blind randomized-withdrawal period showed that patients in the placebo arm had a significant increase in the median weekly number of cataplexy attacks vs those treated with JZP-258 (2.35 [0.00, 11.61] vs 0.00 [−0.49, 1.75], respectively; treatment difference, P <.0001). The placebo arm also demonstrated a significant increase in median ESS score vs JZP-258 (2.0 [0.0, 5.0] vs 0.0 [−1.0, 1.0], respectively; treatment difference, P <.0001). Moreover, both patient and clinician ratings of change in narcolepsy symptoms overall (PGIc and CGIc) indicated worsening in the placebo arm vs JZP-258 (‘Much Worse’ or ‘Very Much Worse’ scores for placebo vs JZP-258: PGIc, 44.6% vs 4.3%; CGIc, 60.0% vs 5.9%; P <.0001 [nominal]).
The safety profile of JZP-258 was consistent with that observed in previous studies. The most common adverse events were headache, nausea and dizziness; 2 patients experienced treatment-related serious adverse events (confusional state and visual hallucination after accidental JZP-258 overdose; muscle enzymes increased 1 day after the end of placebo treatment).
“JZP-258 represents between 1000 and 1500 milligrams daily reduction of sodium for patients currently treated with Xyrem, depending on the dose,” said Robert Iannone, MD, MSCE, EVP, research and development of Jazz Pharmaceuticals. “Given the broad scientific consensus that reducing daily sodium consumption is associated with clinically meaningful reductions in blood pressure and cardiovascular disease risk, we believe that JZP-258 has the potential to be an important treatment option for patients living with the life-long condition of narcolepsy.”
A Prescription Drug User Fee Act (PDUFA) target date of July 21, 2020 has been set for this application.
For more information visit jazzpharmaceuticals.com.