Orexins—the Next Ozempic? The Pharmaceutical Industry Prepares for a Breakthrough in Neuroscience

In early August 2026, the U.S. Food and Drug Administration (FDA) approved Takeda’s overepoxstone (Orzeyful)—the first drug in history to treat pathological sleepiness, or type 1 narcolepsy, by addressing the underlying cause rather than the symptoms. Analysts at Morgan Stanley estimate that the potential market for such drugs will grow to $16 billion by 2035, according to The Economist. However, the potential applications for drugs of this type are much broader—scientists hope they will help treat other sleep disorders, as well as common conditions such as attention-deficit/hyperactivity disorder (ADHD) and depression. This could potentially be a breakthrough on par with the discovery of GLP-1-based weight-loss drugs, such as Ozempic. Who should you keep an eye on in this race?

We spend about a third of our lives sleeping, yet the mechanisms behind this process remain largely a mystery. People had long suspected the power of sleep, even before the emergence of neuroscience. As Aristotle wrote in his treatise *On Sleep and Wakefulness*, sleep is a natural consequence of perception, because the senses require periodic rest. Hippocrates and his students, meanwhile, considered sleep essential for maintaining human health. Dream interpretation was also used as a tool for diagnosing and treating conditions caused by internal sensations.

Modern science agrees on the importance of sleep, but it wasn’t until 1953—when the “rapid eye movement” (REM) phase, during which we dream, was discovered —that it became clear: the sleeping brain isn’t turned off, but simply switched to a different mode.

Disruptions to this sleep-wake cycle are the most widespread—and yet the most “invisible”—medical problem. On the one hand, there is insomnia, which affects nearly one in four adults worldwide. On the other hand, there is its mirror opposite: narcolepsy, when a person suddenly falls asleep during the day, sometimes at the most inopportune moments. Sometimes this is also accompanied by cataplexy—a sudden “shutdown” of the body’s muscles. A person might be laughing at a joke—and suddenly fall to the floor because their muscles have failed. This mechanism (one of many in the complex regulation of sleep and wakefulness) prevents you from beating your spouse with all your might at night if, for example, you dream that you’re fending off a leopard. But in some people, it suddenly kicks in during the day, and for a long time, it was unknown why this happens.

The answer came from an unexpected source—dogs. As described in a review in Frontiers in Neuroscience, in the 1970s, Stanford University maintained a colony of dogs with hereditary narcolepsy: the dogs would fall asleep with joy at the sight of food, literally collapsing on the spot. A young French neuroscientist, Emmanuel Minot, came to California to study these dogs. A nice touch: he still keeps a narcoleptic Chihuahua named Watson from that very colony at home, according to The Wall Street Journal. For ten years, he searched for the cause of the disease and eventually discovered that people with type 1 narcolepsy (NT1) simply lack neurons in the brain that produce a small peptide called orexin (also known as hypocretin).

However, understanding the cause of a disease is one thing, but finding a cure for it is quite another.

The Japanese pharmaceutical company Takeda spent fifteen years conducting research before developing oveporestone. The drug has side effects—insomnia and frequent urination in about one-third of patients—but they proved to be tolerable: more than 95% of patients who completed the study agreed to continue taking the drug, according to Nature.

Nineteen-year-old Tyler Chapman from Tennessee slept 16 hours a day, tried 13 different medications, and drank the equivalent of 10 cups of coffee a day. Then he volunteered for a clinical trial of a new drug—and a few minutes after taking the pill, as he told the WSJ, “it was as if my body had been plugged into an outlet—for the first time in ten years, I felt alive.”

The objective results are also impressive. Patients with NT1 were given a wakefulness test: to sit in a dark, quiet room and stay awake. A healthy person can last 30–35 minutes. An NT1 patient—about 4 minutes. After 12 weeks of taking oveprexstone, the average sleep latency increased from 4 to 20 minutes—meaning patients returned to nearly the normal range. Cataplexy episodes decreased by about three times. Minyo, who led Takeda’s final studies at Stanford, calls this “a complete revolution: the first dose of the drug is like turning on the light in a room.”

Older medications for narcolepsy—stimulants such as modafinil or amphetamines—stimulated certain neurotransmitters (dopamine, norepinephrine), which improved alertness but could cause anxiety, high blood pressure, and the risk of addiction. Oveporexstone works like an “orchestra conductor” who coordinates several wakefulness systems at once, explains The Economist. Instead of plucking a single string at a time, the drug restores the entire orchestra’s harmonious performance. Hence its lower potential for abuse.

Type 1 narcolepsy is a fairly rare condition in and of itself. According to Takeda’s estimates, there are about 60,000 diagnosed patients in the U.S. and roughly the same number who remain undiagnosed. But the brain’s orexin receptors aren’t just responsible for sleep: they also regulate the reward and motivation systems, attention, and overall energy levels. This explains the pharmaceutical companies’ interest.

The first obvious target beyond narcolepsy is ADHD. According to Ryan Sultan, a psychiatrist and researcher at Columbia University (U.S.), about 366 million adults worldwide suffer from this condition—and 85% of them have not even been diagnosed. There are another 47 million children and adolescents under the age of 20, and these are only those who have already been diagnosed. The current market for ADHD medications is $17 billion annually, with the potential to grow to $24 billion by 2030, according to estimates by The Business Research Company.

If we take a broader view—including all sleep disorders, such as insomnia—the scale becomes even more staggering. A systematic review published in 2025 in *Sleep Medicine Reviews* estimated the global prevalence of clinical insomnia: 852 million adults, or 16.2% of the world’s population, with an additional 415 million suffering from severe insomnia. The total market for sleep disorder medications is estimated at $33 billion and is projected to grow by 14% annually, with the potential to reach $65 billion by 2030. Narcolepsy, with its current $3 billion market, is not even the tip of the iceberg.Now it’s clear why Mario Accardi, CEO of Centessa—a startup developing orexins—directly refers to this class as “GLP-1 neuroscience.” Incidentally, the market for GLP-1-based diabetes and obesity drugs is estimated at $80 billion, with projections of growth to $185 billion by 2033.

The race is already on. In March 2026, Eli Lilly announced the acquisition of Centessa Pharmaceuticals for $6.3 billion (up to $7.8 billion, including potential additional payments) for cleminorexton, an orexin for various types of narcolepsy that is already in the final Phase III of clinical trials.

Alkermes, with its drug alixorexone for the treatment of all types of narcolepsy, is also already in Phase III, and is testing promising molecules for the treatment of ADHD in Phase I.

According to *Nature*, there are currently 11 orexin-based drugs in various stages of clinical trials, and this is clearly just the beginning.

Takeda is currently in the lead, but as we know, the pioneer doesn’t always reap the biggest rewards. Novo Nordisk was the first to bring GLP-1-based drugs for diabetes and obesity to market, and Ozempic, in particular, made the Danish company a legend. However, Eli Lilly now takes the lion’s share—it holds 61% of the U.S. market, compared to Novo’s 39%, according to CNBC.

History may repeat itself with orexins: Takeda has made its mark, but Lilly—with its $7.8 billion bet on Centessa and broader indications—may well take the lead. Or it could be someone else we don’t know about yet—in any case, the orexin story is one that the whole world will be watching with great interest. And with the hope of finally overcoming depression and getting a good night’s sleep.

This article was AI-translated and verified by a human editor