A clearer path to relief: sinusitis treatments on the way 

Sinusitis is an inflammation of the tissues lining the sinuses. These are cavities in the skull that help filter air, as they produce mucus to trap germs. Sometimes, after a cold or the flu, the drainage of the mucus becomes blocked, causing its buildup, allowing germs to grow, and leading to congestion and pain. Investments have been flowing to come up with emerging sinusitis treatments as there remain unmet medical needs despite existing therapies. This past year has been mixed bag of successful clinical trials and letdowns. But soon, the potential approval of Dupixent could shift the standard of care for patients. 

Emerging sinusitis treatments: Dupixent approval date nears 

The medicine currently being deliberated by the U.S. Food and Drug Administration (FDA) is Dupixent, a monoclonal antibody. Developed by big pharmas Sanofi and Regeneron, Dupixent could lock in its ninth approval in February for allergic fungal rhinosinusitis for adults and kids above the age of five. Allergic fungal rhinosinusitis is a kind of sinusitis that develops as an allergic reaction to inhaling fungus, leading to chronic inflammation. It is driven by a hypersensitivity response that is often associated with asthma and allergic rhinitis. 

Dupixent is designed to block two proteins, namely, interleukin-4 and interleukin-13, which are the main drivers of inflammation in the sinuses. This way, it aims to slow the production of mucus, shrink nasal polyps, improve congestion, and restore the sense of smell.   

The potential FDA clearance would be based on positive phase 3 trial results where the antibody met the primary endpoint. It was found that nasal congestion – a stuffy nose – improved by 50% in the treatment group compared to 9.8% in the placebo group after 52 weeks. An endoscopy – a procedure done to view internal body structures – found that nasal polyps, which are growths on the sinuses linked to rhinosinusitis, reduced by 60.8% in the Dupixent cohort compared to 15.2% in the placebo group after 24 weeks.  

The monoclonal antibody was first authorized to treat adults with chronic rhinosinusitis nearly seven years ago, and since then, the approval expanded to adolescents in 2024 as well as a host of other inflammatory conditions like atopic dermatitis.  

Clinical fails plague therapeutic space 

The promising trial is surely a step up from unwelcome news of drug fails in recent times. Massachusetts-based Lyra Therapeutics abandoned its chronic rhinosinusitis drug LYR-210. It is a mini bioresorbable device that is implanted deep in the nasal passages, where it delivers mometasone furoate, an anti-inflammatory steroid, for up to six months.  

The drug failed a phase 3 trial in 2024 but climbed back up the ranks when it did well in a phase 3 trial for people with chronic rhinosinusitis without nasal polyps in June. With $22.1 million stocked up, it was meant to stay afloat well into 2026, however, the company announced that it was stalling LYR-210’s development. This decision came with layoffs. 

Likewise, New Jersey-based Insmed ditched its rhinosinusitis program following a disappointing phase 2 trial in December. The small molecule Brinsupri – approved by the FDA to treat treatment of non-cystic fibrosis bronchiectasis, a chronic lung disease, in August – failed to meet primary and secondary endpoints, with placebo having fared better in the study. 

Monoclonal antibodies for sinusitis: more the merrier? 

Although these were notable losses in the therapeutic field, monoclonal antibodies seem to have struck lucky this past year. The drug tezepelumab-ekko, for instance, known by its brand name Tezspire, was greenlit by the FDA in October for chronic rhinosinusitis with nasal polyps. The monoclonal antibody had already nabbed approval to treat severe asthma in 2021.  

The sinusitis approval comes after the AstraZeneca and Amgen-owned medicine demonstrated a statistically significant and clinically meaningful reduction in the severity of nasal polyps and showed near-elimination of the need for surgery and a significant reduction in systemic corticosteroid use compared to placebo.  

While Dupixent blocks interleukin-4 and interleukin-13, Tezspire targets a different pathway that is linked to inflammation. It binds to thymic stromal lymphopoietin (TSLP), a cytokine – small proteins that act as chemical messengers to coordinate immune responses. When TSLP is blocked, inflammation is, in turn, reined in.  

The president and chief executive officer (CEO) of the Asthma and Allergy Foundation of America, Kenneth Mendez, pointed out that Tezspire’s approval changes how people with sinusitis may no longer have to solely rely of steroids to get better. 

“Chronic rhinosinusitis with nasal polyps is a persistent and often-overlooked disease that can significantly impact daily life, robbing patients of their ability to breathe without congestion and full sense of smell. This approval introduces an innovative treatment option for patients with the potential to help address the ongoing cycle of debilitating symptoms, surgeries and systemic steroid use,” said Mendez, in a press release. 

GSK’s depemokimab awaits FDA approval for chronic rhinosinusitis

Moreover, pharma giant GSK’s depemokimab, a monoclonal antibody that targets the cytokine interleukin-5 – present in up to 85% of people with chronic rhinosinusitis with nasal polyps – met primary endpoints in two phase 3 trials last year. The drug, which is given twice a year, showed clinically meaningful and statistically significant improvements in nasal polyp size and nasal obstruction. Both are key symptoms of rhinosinusitis. At the time, GSK was gearing up for depemokimab’s premiere in the market to treat rhinosinusitis and asthma, as the FDA decision date was scheduled for December 17th, however, it was only cleared for asthma, with the FDA silent about a potential rhinosinusitis one. 

As the regulator continues to review the medicine in 2026, it is hoped that depemokimab, now known by its brand name Exdensur, could piggyback on its asthma approval for a speedy decision on rhinosinusitis. 

Upstream Bio’s verekitug sees phase 2 success in rhinosinusitis study 

Meanwhile, Massachusetts-based Upstream Bio’s monoclonal antibody verekitug is in the clinic to treat respiratory conditions, including rhinosinusitis, and it is moving full steam ahead following positive phase 2 trials results published late last year. 

The study met its primary endpoint, having demonstrated a statistically significant and clinically meaningful reduction in nasal polyp score of -1.8 after 24 weeks. This is a measure of the size of nasal polyps ranging from zero to four for each nose, with zero indicating that no nasal polyps are visible. The antibody also reduced congestion in the nose and cut the need for patients to undergo surgery of steroids by 76%. 

Verekitug is thought to potentially take on monoclonal antibodies in the market, like Novartis’ Xolair and Sanofi’s Dupixent, and Tezspire. And it could very well do so as Upstream has claimed that verekitug is around 300 times more potent than Tezspire. 

As therapies like verekitug are aimed at improving the quality of life and scaling down the dependency on steroids, Joseph Han, professor in the Department of Otolaryngology & Head and Neck Surgery and the chief for the Division of Allergy at Old Dominion University and principal investigator on the phase 2 trial, said in a press release: “The improvements observed with verekitug, including durable nasal polyp reduction and symptom relief with a treatment potentially administered only four times per year, are encouraging. These results suggest verekitug could represent a meaningful advancement in the treatment of this chronically debilitating condition.” 

As monoclonal antibodies seem to be the frontrunners for research and development (R&D) in the space at present, challenging steroids, early-stage findings on microbiome health and therapies to restore the microbiome could have a bright future.  

How influential is the microbiome in sinus infections? 

Meanwhile, a similar idea to fecal microbiota transplant (FMT), which has gained popularity as an effective treatment against Clostridioides difficile infections – the bacteria responsible for causing diarrhea – nasal microbiome transplant could address rhinosinusitis. By transferring the microbiota present in the nose from a healthy donor to a person with sinusitis, this could tackle infections, as it would be able to control mucus production spawned by infection-causing pathogens. 

It is believed that it could benefit people with chronic rhinosinusitis who are resistant to standard antimicrobial therapies, but scientists have called for further long-term safety and efficacy studies.  

“A deeper understanding of the mechanisms underlying microbiota–host–pathogen interactions in the nasal cavity is required to capitalize on the benefits of treatments based on NMT. Preclinical animal models, in particular germ-free animals intranasally colonized with the defined nasal microbiota, will be instrumental in elucidating the mechanistic pathways that the nasal microbiota follows upon transplantation. By leveraging the advances and lessons learned from FMT, it may be possible to establish a robust framework for the development of safe and effective NMT-based therapies in the future,” the paper published in the journal, Trends in Microbiology, read. 

With Dupixent’s approval date for fungal rhinosinusitis fast approaching, an FDA approval could do wonders for people who haven’t responded well to standard treatments. And the various monoclonal antibodies in the clinic signal a promising class of therapies ready to take on current standards of care for an inflammatory condition that affects about 28.9 million people in the U.S.