There’s hope on the horizon for the hordes of people worldwide who suffer from sleep apnoea as Apnimed, the $400m company behind the first ever pill to treat it, prepares to file for FDA approval, reports Forbes.
In November 2016, Harvard researcher Dr Luigi Taranto Montemurro was in a lab at Brigham and Women’s Hospital observing the sleep of a middle-aged man with obstructive sleep apnoea, who lay in a bed attached to wires to track whether he stopped breathing overnight.
Montemurro was testing a potential medication, but didn’t expect much. Researchers had been trying for decades to invent a drug that could fix the common condition – in which breathing pauses during sleep, sometimes lowering oxygen levels to a dangerous degree – and every earlier effort had failed.
Then he realised the sleeping man was breathing normally.
“Usually this guy was full of apnoeas – but suddenly he was breathing well. So I went to see if something was off on the equipment that it was not connected properly,” Montemurro said.
But the hook-up was fine. The combination of two existing drugs he’d been testing had worked. “I couldn’t believe my eyes,’” he said.
Fast forward nine years later, and Massachussets-based start-up Apnimed, which acquired the rights to the potential medication from Harvard, is preparing to file for FDA approval for a nightly pill based on those two drugs for the breathing disorder.
In simplified terms, it works by waking up the brain stem, preventing full muscle relaxation in the throat, while allowing the brain itself to rest during sleep. If all goes well, it could be on the market in the first half of 2027, offering a potentially life-changing treatment for some of the millions of people suffering from the condition.
Right now, the primary treatment for the disease is a continuous positive airway pressure machine, known as a CPAP, which forces air down the wearer’s throat to keep it open. The device works. But, no surprise, it’s hated by most users. Many people with sleep apnoea refuse to try it or won’t even get diagnosed for fear they may have to.
Yet sleep apnoea isn’t just some minor annoyance. Research shows that people with untreated sleep apnoea are more likely to develop heart trouble, strokes and perhaps even Parkinson’s and Alzheimer’s. A treatment that’s easier for patients to stomach could have a transformative impact on their overall health.
Apnimed is an early-stage biotech, meaning it’s losing money and has no revenue yet. But the promise of the pill has helped it to raise $260m from investors at a valuation of around $400m. If it succeeds in releasing the drug, it could be worth a lot more.
Sleep apnoea, despite there now being a handful of other early-stage start-ups focused on it, is a disease that’s under the radar. “It’s not an exciting disease,” Dr Larry Miller, Apnimed’s co-founder and CEO, said. “Some, like Alzheimer’s, capture the public imagination. This one never did.”
That may be because sleep isn’t that well understood, even though we spend about one-third of our lives doing it. Or because of the false perception that it’s not a serious disease, or solely a problem for obese, middle-aged men.
CPAP dates only to 1981; before that people with severe sleep apnoea were treated with tracheostomy, a surgical hole in the windpipe.
“Obstructive sleep apnoea is a massive public health problem that is under-recognised, under-treated and under-diagnosed,” said Dr Nate Watson, a sleep medicine doctor and former President of the American Academy of Sleep Medicine (who has done some consulting with Apnimed).
A treatment for sleep apnoea had long been a dream for Harvard sleep researcher Dr Andrew Wellman, who runs the Sleep Disordered Breathing Lab at Brigham and Women’s Hospital where Montemurro was a post-doc.
Even as a young research fellow 25 years ago, Wellman had hoped to devise a treatment for sleep apnoea. He knew there had to be a chemical component to the disorder – and potentially a pharmaceutical fix – because even people who are extremely obese with large tongues and thick necks don’t suffer from sleep apnoea when they’re awake.
But at least 40 drug candidates have been tested for obstructive sleep apnoea over the years without success, Miller said.
“A pill for the condition has always been the holy grail,” Wellman said.
That’s why he and Montemurro, who’d grown up in the small Italian town of Rovato and come to the US to work in his lab, were so shocked when the testing on patients showed signs that it worked.
“I honestly didn’t believe our findings were real,” Wellman said. “I had been fooled so many times in the past with this.”
When Montemurro told him about the results in the lab, he contacted Miller, a pulmonologist and serial entrepreneur. Miller had already founded nine other companies since 1990, seven of which he ultimately sold, for millions.
When he spoke to Wellman, he was at Macrolide Pharmaceuticals, which he’d launched in 2015 with funding from the venture arms of Novartis and Roche, and big plans to develop a new type of antibiotics.
But the firm later struggled, and wound up being sold, under a new name and with a new business focus, to another early-stage pharma company, in 2021.
“It’s an addiction, look at it that way,” said Miller (72) of his start-ups. “Before this one, I thought I was done. … But when Andrew called me about the data, I thought, ‘This is too good. I have to do it’.”
In 2017, Miller launched Apnimed, negotiating the rights to the patents from Harvard, with Montemurro joining as co-founder and, later, chief scientific officer. The start-up raised $26m from an investment firm in 2019, and Miller now owns what he calls a “small percentage” of the business.
“These guys are the real deal,” said Dr John Cronin, who joined the company as senior vice president of clinical development in 2022 after working as chief medical officer in sleep and respiratory care at Philips Respironics, one of the two big CPAP makers.
Over the past eight years at Apnimed, Montemurro and his scientific team have tested and refined the two-drug pill. Phase 3 clinical studies, which wrapped up last year, showed that it worked to improve patients’ breathing overnight.
In one of those studies, reported last July, the drug reduced a measure of the severity of sleep apnoea, known as the apnoea-hypopnea index, by 47% at 26 weeks (versus 7% for a placebo) with no serious adverse events. The drug’s side effects include minor issues such as dry mouth and insomnia.
There are no other pill treatments for sleep apnoea that work for everyone. At the end of 2024, the FDA approved Eli Lilly’s weight-loss drug Zepbound for the treatment of moderate-to-severe sleep apnoea in adults who are obese.
Unlike Apnimed’s pill, Zepbound works for sleep apnoea because people who are overweight are more likely to suffer from it, so losing weight can help their breathing overnight. It does not treat the sleep apnoea directly, and is not approved for mild sleep apnoea or for people who are not obese.
Apnimed figures that the number of untreated people with sleep apnoea is so high that having more treatment options will only increase the potential market. An analysis the company did of five years of medical claims found 23m people with a sleep apnoea diagnosis – a small percentage of those believed to have the disease – but only 6.5m people are filing for treatment.
“We believe most people who are diagnosed are not being treated. That’s the fundamental absurdity of the category,” said Apnimed chief commercial officer Graham Goodrich.
The company is already talking with insurers about coverage, which is key to the pending drug’s success. And beyond its first pill for sleep apnea, Apnimed is working on two other potential molecules for sleep apnoea in partnership with Japanese pharmaceutical firm Shionogi.
In the future, Miller believes that the millions of people with the condition will have treatment options, just as they do for other major diseases and disorders.
“It will be like asthma or high blood pressure,” he said, ticking off major chronic diseases for which pharmaceutical treatments are available. “As a physician you try to choose the best option for the patient. That hasn’t been possible until now.”
Forbes article – A 'Holy Grail' Sleep Apnoea Pill Could Be On The Market Next Year (Open access)
See more from MedicalBrief archives:
Tirzepatide effective for obstructive sleep apnoea – US study
Sleep apnoea breathing pauses reduced with sulthiame – Swedish trial
Active lifestyle may help protect against obstructive sleep apnoea