Competition is on the horizon for costly narcolepsy treatments

R&D
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People who live with narcolepsy — about one out of every 2,000 Americans — don’t have many options when it comes to treatment. The milder form of narcolepsy includes symptoms of excessive daytime sleepiness and can be treated with a stimulant like Provigil, Adderall, or Dexedrine in order to get people through their day.

In addition to excessive daytime sleepiness, up to 60% of narcolepsy cases include cataplexy, which is a sudden loss of muscle control. When patients experience intense emotion, either positive or negative, they are rendered unconscious.

Without being properly diagnosed and treated, there is no amount of focus, concentration, or alertness that can stave off cataplexy. For years, Jazz Pharmaceuticals has dominated the market in treating narcolepsy with cataplexy. But increased competition is on the horizon.

Classic treatment options

Sodium oxybate — which in the late 1980s was marketed to bodybuilders and then became known as GHB and criminally used as a date rape drug — has been sold under the brand name Xyrem after gaining FDA approval in 2002. In order to bring it to market, a special program called Risk Evaluation and Mitigation Strategy (REMS) had to be put in place, where only eligible patients could access the drug through a very strict process.

Both the physician and the patient have to be registered and the drugs can only come from a primary source through limited distribution. This is a practice very common among cancer drugs.

Other than the reputation and infamous notoriety of the drug, Xyrem had another drawback. It contains 109% of the American Heart Association’s ideal daily allowance for sodium intake. In 2020, and in an attempt to abate the drawback, Jazz got FDA approval for Xywav, which is a mixture of calcium, magnesium, and potassium salts that contains 92% less sodium than Xyrem.

Wake up and go to sleep

The irony of these two narcolepsy drugs that work to normalise the sleep-wake cycle is that they have to be taken twice per night. Patients have the first dose before they go to sleep, then wake up two and a half to four hours later for the second.

Taking the drug at bedtime allows patients to sleep through the night, with the second dose carrying them through a night of restful sleep. As a result, they shouldn't have as many symptoms the next day.

Pulling an all-nighter

The latest breakthrough in the narcolepsy space seeks to remedy the inherent counterproductivity that comes along with the Xyrem and Xywav dose schedule. Avadel Pharmaceuticals developed Lumryz, a sodium oxybate that is a once-daily, extended-release oral suspension that gained tentative FDA approval in July 2022.

Tentative approval means Lumryz has satisfied all the FDA requirements for efficacy, safety, and quality standards, but it can’t be fully approved until a patent or other exclusivity expires.

Two decades of exclusivity

Jazz Pharmaceuticals has numerous patents on sodium oxybate and, through litigation, has maintained market exclusivity for many years.

Despite Xyrem being originally approved in 2002, Jazz has remained unencumbered in the market by patenting materials and processes related to Xyrem along the way. That’s an objectively long time to have exclusivity of a drug that was first synthesised nearly 100 years ago.

Competition starts to heat up

Harmony Biosciences introduced Wakix to the market in 2019 as the first non-controlled substance for the treatment of narcolepsy. This initial approval was only for treatment of excessive daytime sleepiness.

In 2020, the FDA-approved indication was expanded to include those patients who suffer from cataplexy. Taken once daily after waking up in the morning, Wakix exerts its effects by promoting wakefulness, but does not have any effect on sleep architecture. Unfortunately, there are no head-to-head clinical trials comparing Wakix to Xyrem or Xywav for treatment of cataplexy.

Monopoly money

In a case filed in California in 2021, Molina Healthcare claimed Jazz Pharmaceuticals engaged in a “comprehensive anticompetitive scheme to suppress generic competition for Xyrem,” abused the REMS program, and “engaged in sham patent litigation.”

Furthermore, Molina stated Jazz “suppressed generic competition and raised the price of Xyrem 841% between 2007 and 2014.” In 2007, Xyrem had an annual cost of $11,169, but in seven short years the cost had jumped to $106,215. Currently, the annual cost of Xyrem is $182,804, while Xywav is a little less at $168,508. Introduced much later, Wakix has not undergone any major price hikes, but it also sits at a staggering $165,587 per year.

One more hurdle to clear

For Avadel’s Lumryz, the one-dose extended-release oral suspension that allows narcolepsy patients to sleep through the night, the worst-case scenario is it won't be on the market until 2025. The best-case scenario? Jazz and Avadel settle in court soon, giving people with narcolepsy another option for treatment.

The last patent currently in litigation is Jazz’s REMS program. In short, Jazz patented their version of an FDA requirement. If anyone is wondering if it’s common practice to patent a Risk Evaluation and Mitigation Strategy, there are currently 62 medications that require a REMS. Xyrem is one of three that has a patent.

About the author

Jason PetersonJason Peterson RPh is a clinical pharmacist at RemedyOne, with over 25 years of experience in healthcare and pharmacy.

Mike Hammerton

14 December, 2022