Sleep apnea: biotechs snore points in the therapeutic space (2024)

There is a lot of research out there, including clinical trials, aimed at combating sleep apnea, a serious sleep disorder. From medical tools such as CPAP machines and mouth guards to throat exercises for sleep apnea, there are various ways to relieve symptoms like snoring, daytime sleepiness, and disruptions in brain function. While these are effective techniques, therapeutic strides are proving to help address different stages of the disease.

Sleep apnea occurs when the airways narrow or close when sleeping, making it hard to breathe. While the root cause varies depending on the person, there are three kinds of the disease that can be treated. The most common form is obstructive sleep apnea (OSA), which happens when throat muscles relax and block the flow of air into the lungs. Central sleep apnea (CSA) has to do with the central nervous system and occurs when the brain doesn’t send proper signals to the muscles that control breathing. And then there is treatment-emergent central sleep apnea. Also called complex sleep apnea, it actually manifests as a side effect of medicines taken by someone who has already been diagnosed with OSA.

Across the world, 936 million adults are estimated to have mild to severe OSA, according to a report by the National Council on Aging. Untreated forms of the disease can lead to heart, kidney, and metabolic health complications, which is why treating sleep apnea as early as possible is crucial.

Lilly’s weight loss medicine tirzepatide hits two milestones in clinical trial for sleep apnea treatment

Weight loss medicines – which sparked a buying spree a year ago – have shown benefit in driving down sleep apnea symptoms. Pharma giant Lilly’s tirzepatide chalked up positive results in two studies earlier this year. Both phase 3 trials met all primary and secondary endpoints and the drug achieved a decline in mean apnea-hypopnea index (AHI) of up to 63%. The AHI is a metric used to diagnose and determine the severity of sleep apnea.

In the SURMOUNT-OSA Study 1, which tested the drug on patients not using CPAP machines, tirzepatide had a mean reduction from baseline of 27.4 events per hour, compared to 4.8 for placebo. The drug also led to a decrease in mean body weight of 18.1% from baseline, compared to 1.3% from baseline for placebo. Since being overweight and obese are major risk factors for OSA, this measure is a helpful indicator of disease manifestation as well.

In the SURMOUNT-OSA Study 2 for patients on CPAP, there was a mean reduction of 30.4 events per hour compared to 6 for placebo. Moreover, patients experienced a mean weight loss of 20.1% on tirzepatide versus 2.3% for those on placebo.

As 85% of OSA cases go undiagnosed and therefore untreated, Jeff Emmick, senior vice president of product development at Lilly said: “Addressing this unmet need head-on is critical, and while there are pharmaceutical treatments for the excessive sleepiness associated with OSA, tirzepatide has the potential to be the first pharmaceutical treatment for the underlying disease.”

Lilly is currently waiting for the U.S. Food and Drug Administration’s (FDA’s) decision to expand the use of tirzepatide to treat OSA after it filed an application back in June.

Epilepsy drug sulthiame finds new purpose in sleep apnea clinical trial

Besides weight loss medicines being evaluated in other indications like sleep apnea, it is increasingly common to test already-approved drugs across indications, just like the epilepsy drug sulthiame, which recently showed promise in sleep apnea. The anticonvulsant drug inhibits the enzyme carbonic anhydrase, which helps maintain the acid-base balance in the brain. By doing so, it curbs bursts of electrical activity – a hallmark of epilepsy. While it was launched under the brand name Ospolot in Europe back in the 1960s, these drugs are now being investigated in the sleep apnea space.

An international clinical trial involved 298 people with OSA – in Spain, France, Belgium, Germany and the Czech Republic – who were not on CPAP machines.

“The standard treatment for obstructive sleep apnoea is sleeping with a machine that blows air through a face mask to keep the airways open. Unfortunately, many people find these machines hard to use over the long term, so there is a need to find alternative treatments. We also need a better understanding of the underlying mechanisms in OSA to help clinicians give more personalized treatment,” said Jan Hedner from Sahlgrenska University Hospital and the University of Gothenburg in Sweden, at the European Respiratory Society (ERS) Congress in Vienna in Austria.

The drug was meant to cut down the number of breathing interruptions during sleep and to improve oxygen levels. As patients with OSA often snore loudly, their breathing starts and stops during the night, and they tend to wake up several times. Not only does this cause tiredness, but it can also increase the risk of high blood pressure, stroke, heart disease and type 2 diabetes, according to the European Respiratory Society (ERS).

The inhibitor drug exhibited a 17.8% drop in AHI among patients on the lowest dose (100 mg), a 34.8% decline on the medium dose (200 mg), and 39.9% on the highest dose (300 mg). To add to that, breathing interruptions waned by 50%. Side effects were not severe but included pins and needles, headache, fatigue, and nausea.

“This is one of the first studies to suggest that a drug treatment could help some patients, and the results are promising. We need to continue testing sulthiame and other treatments to understand their long-term effects, including any side effects. For example, we’d like to see whether treatment can help with lowering blood pressure and preventing cardiovascular disease for people with OSA,” said Sophia Schiza, head of the ERS assembly on sleep disordered breathing.

Researchers pointed out that a larger phase 3 clinical trial would need to be held to truly understand the benefits of the drug for sleep apnea.

AD109: Apnimed completes phase 3 enrollment for sleep apnea

Meanwhile, Massachusetts-based Apnimed has pledged to breathe “new life into sleep-related diseases.” Much of its efforts are going into the development of its clinical candidate AD109. It is designed to target a type of nerve cells called hypoglossal motor neurons (HMNs), which control the upper airway muscles as well as the tongue muscles. This improves the signals that are sent to the airway during sleep so as to prevent the collapse of this airway and allow more oxygen to enter the body in people with sleep apnea. The pill is meant to be taken once a night and is a combination of the antimuscarinic aroxybutynin and a selective noradrenaline reuptake inhibitor (NRI).

Antimuscarinic drugs and NRIs together have been known to turn down the severity of sleep apnea. Apnimed finished enrolling patients for AD109’s phase 3 SynAIRgy study two months ago.

“We believe the strong interest we have seen throughout the SynAIRgy Study is telling of the sleep community’s desire for new treatment options,” said Patrick Strollo, Chairman of the SynAIRgy clinical study and Vice Chair of Medicine for Veterans Affairs at the University of Pittsburgh School of Medicine. “Millions of people living with OSA refuse, abandon, or are dissatisfied with their current treatment, and this phase 3 trial offers them new hope.”

There is optimism around the phase 3 study as the phase 2 trial that ended last year hit the main goal.

“MARIPOSA results also showed that AD109 improved daytime fatigue, an often-debilitating effect of poor sleep due to OSA,” said Paula Schweitzer, an investigator in the MARIPOSA trial and the director of Research at St. Luke’s Sleep Medicine and Research Center in Missouri. “For those who cannot tolerate current treatments, AD109 has the potential to be a convenient, oral pill that could improve people’s quality of life both at night and during the day.”

Patients who received the 2.5mg/75mg dose of the drug had an AHI4 (a 4% or greater oxygen desaturation in hypopneas) reduction from 20.5 events per hour to 10.8. Unlike an apnea, which is when the complete blockage of the airway stops breathing, hypopnea is the partial blockage of the airway for at least 10 seconds. Around 44% of people had a greater than 50% reduction from baseline, and 15% of treated patients had at least an 80% reduction. There were no serious adverse events recorded.

The ongoing phase 3 trial is backed by a $79.75 million extended series C financing round held early last year.

This comes just as Japanese multinational Takeda canned its sleep apnea clinical trial assessing TAK-925, an orexin-2 receptor agonist that promotes wakefulness, owing to slow enrollment. However, this doesn’t come as a surprise since the narcolepsy drug has been through ups and downs in the clinic, having bumped into enrollment and data collection issues.

Besides Lilly and Apnimed, Basel-based Mosanna Therapeutics’ early-stage small molecule MOS-118 is also being trialed and a seed extension will help propel its development.

While much is yet to be disclosed about how MOS-118 is getting on – discovered by French pharma giant Sanofi – Jonathan Talbot, Mosanna’s co-founder and chief executive officer (CEO), said in a press release: “I’m excited to develop a treatment for one of the modern world’s growing, global health crises. Mosanna aims to bring the first, targeted precision medicine to obstructive sleep apnea patients with a focus on the devastating cardiometabolic impact of this disease.”

Patient-specific approaches might be the way to go

Although there aren’t a whole lot of biopharma startups up and about in the space, ongoing research conveys that poor gut microbiome could be a grave effect of sleep apnea. A study published in Nature suggests that when the airway collapses in patients with sleep apnea, making it hard to breathe, it can lead to the destruction of the intestinal barrier, and therefore, gut dysbiosis – a change in the composition of the gut flora.

In fact, an uptick of certain bacteria like Fusobacterium and Megamonas was linked to the severity of sleep apnea in patients. This altered gut flora can result in inflammation associated with sleep apnea. The study offers more insight into why multiple organs may be affected in patients with OSA as well as the need for targeted therapies based on people’s microbiome profiles.

As this research could fuel therapeutic advances in the field, we can hope that the few sleep apnea-focused biopharmas don’t plan on hitting snooze on clinical development, and patient-specific therapies come into focus soon.

Schiza, at the ERS Congress, said: “Many of us know that we snore or that our partner snores. If snoring is accompanied by other symptoms, such as waking up often in the night, feeling fatigued and/or sleepy during the daytime, then it’s time to speak to a doctor. Because obstructive sleep apnea increases the risk of serious health problems such as high blood pressure, heart and metabolic disease, it’s vital that we diagnose and treat the condition. Treatments are available, but because they don’t work for everyone, we need more ways to treat the disease, based on individualized diagnostic and treatment approaches.”