- Investors aren't hitting snooze on Jazz Pharmaceuticals, especially now that its sleep disorder drug has shown a strong efficacy profile across a trio of late-stage studies.
- The company on Tuesday revealed more complete data from the Phase 3 trials, collectively part of the TONES program, that showed higher doses of JZP-110 markedly improved the amount of time it takes patients who have either narcolepsy or obstructive sleep apnea (OSA) to fall asleep, as well as their general daytime sleepiness.
- The Dublin-based drugmaker plans to file a New Drug Application for its candidate in late 2017. Following the positive readouts, shares of the company rose almost 4% on June 7, closing at $150.61 apiece.
JZP-110 stands to give Jazz another marketed sleep drug. Xyrem (sodium oxybate), a treatment for cataplexy and excessive daytime sleepiness in narcolepsy patients, is the company's biggest revenue driver, bringing in more than a billion dollars last year.
While Xyrem is clearly doing fine on its own, a new addition would give Jazz further advantages over other sleep drug developers like Teva. The Israeli company, though, is still reeling from the loss of patent exclusivity for its drug Nuvigil (armodafinil). Last year, the medicine saw generic competition from Mylan, which prompted Teva to decrease investment in the drug, according to its most recent annual report. Nuvigil revenues dropped 75% in 2016 as a result of those developments, bringing in just $25 million total.
Jazz's new offering is promising, in good part because of the large effect sizes it has generated in the clinical setting, according to a note from EvercoreISI analyst Umer Raffat. Also notable, Raffat said, is the drug's safety at the 150 mg dose and the fact that efficacy starts to be seen within the first week of it being administered.
TONES 2 enrolled nearly 240 patients with narcolepsy who demonstrated excessive sleepiness and evaluated three doses of Jazz's drug — a 75 mg, a 150 mg and a 300 mg — against placebo. On average, participants receiving the two higher doses took significantly more time to fall asleep than those in the control arm, as measured by the Maintenance of Wakefulness Test (MWT). The mean times to doze off for those groups were 9.8 minutes, 12.3 minutes and 2.1 minutes, respectively.
Sleep latency was a co-primary endpoint in TONES 2. The other was patients' scores on the Epworth Sleepiness Scale (ESS), a gauge for daytime sleepiness, and how they changed from baseline to 12 weeks. Mean scores dropped significantly across all the dosing levels, according to a June 6 statement from Jazz. They fell by 6.4 in the 300 mg group, by 5.4 in the 150 mg group and by 3.8 in the 75 mg group compared to 1.6 in the placebo group.
The 75 mg dose, however, did not hit statistical significance as measured by MWT.
A little more than 80% of the enrolled patients completed TONES 2. Ten discontinued the trial due to treatment emergent adverse events, which included anxiety, headache and nausea. One patient exited after demonstrating serious cases of non-cardiac chest pain and anxiety, though study investigators didn't attribute the events to JZP-110 treatment. Jazz said the safety and tolerability of its drug was consistent with earlier, Phase 2 results.
TONES 3 and 4, meanwhile, focused on patients with OSA who demonstrated excessive sleepiness. The former had the same treatment arms as TONES 2 plus a 37.5 mg group. The latter was divided into two phases; during the first, investigators gave participants as much titrated dose as they could tolerate for two weeks, then put them on a stable regimen for two weeks. If patients showed improvement on the MWT or ESS, they could enter into a placebo-controlled, two-week withdrawal phase.
Again, results from TONES 3 showed the 150 mg and 300 mg doses of JZP-110 significantly increased the time it took participants to fall asleep, and all doses led to lower ESS scores. TONES 4, however, demonstrated that sleep latency and ESS scores got worse for patients who investigators switched to placebo treatment after week four. The preceding study had seven serious adverse events related to treatment, while the latter had none.
The late-stage TONES program has a fourth and final study, appropriately named TONES 5, that has yet to read out because it is a long-term safety and efficacy management trial.