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Tezepelumab trial demonstrates solid results for treatment of CRSwNP

One of the most recent trials for tezepelumab showed strong results in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). The WAYPOINT trial of tezepelumab vs placebo demonstrated statistically and clinically significant score reductions for nasal congestion, nasal polyps, loss of smell, sinonasal outcome test (SNOT-22), Lund-Mackay, and total symptoms. Nasal polyp surgery indications nearly disappeared in the tezepelumab arm (HR = 0.02 [95% CI, 0.00-0.09]), and corticosteroid use fell sharply (HR = 0.12 [95% CI, 0.04-0.27]).

Joseph K. Han, MD
Joseph K. Han, MD

“Biologics have changed the way health care providers treat nasal polyps,” said Joseph K. Han, MD, Vice-Chair of Clinical Affairs, Professor of Otolaryngology – Head and Neck Surgery, and Chief of Allergy at Virginia Health Sciences at Old Dominion University. Dr. Han was the international coordinating investigator and first author for WAYPOINT.

Competing biologics

“Nasal polyps and asthma have very similar pathophysiology, cytokines profile, and inflammatory cascade,” he said. “All of the biologics for asthma clinical studies have similar results for their primary end point, annual rate of exacerbations.”

Currently, there are no completed head-to-head studies comparing biologics for CRSwNP, though some are underway. The EVEREST trial (NCT04998604) will compare dupilumab vs omalizumab, and the TORNADO trial (NCT05942222) will compare dupilumab vs mepolizumab. Additionally, the ANCHOR-1 and ANCHOR-2 studies showed that treatment with depemokimab, an ultra-long-acting biologic targeting IL-5, resulted in improvement in nasal polyps and obstruction scores.

As far as where tezepelumab comes into play, Dr. Han stated that, in his opinion, “if you look at nasal polyp studies, dupilumab and tezepelumab have the biggest change in nasal polyp score and improve the sense of smell quickly. Also, tezepelumab has the highest change of SNOT-22 from baseline of any other biologic studies for nasal polyps.”

Dupilumab, mepolizumab, and omalizumab all carry indications for nasal polyps as well as asthma. Dupilumab is also approved for COPD. Dr. Han noted that clinicians have the longest experience with omalizumab because it was the first of the three to be approved for asthma use in the United States.

The US Food and Drug Administration initially approved omalizumab for asthma in 2003. Many clinicians used the agent for nasal polyps long before the indication was added to the label in 2020. Dupilumab was approved for nasal polyps in 2019 and mepolizumab in 2021. Tezepelumab could be next, although the manufacturer has not announced plans to request the additional indication.

WAYPOINT results

A total of 408 patients with physician-diagnosed, symptomatic, severe CRSwNP were randomized to tezepelumab (203 patients) or placebo (205 patients) plus standard of care and followed for 52 weeks. The trial included 112 sites across 10 countries.

Patients in the tezepelumab arm showed a -2.07-point drop in total nasal polyp score (95% CI, -2.39 to -1.74) and -1.03-point drop in nasal congestion score (95% CI, -1.20 to -0.86). Tezepelumab also improved loss of smell score by one point (95% CI, -1.18 to -083), SNOT-22 total score by 22.26 points (95% CI, -32.32 to -22.21), Lund-Mackay score by 5.72 points (95% CI, -6.39 to -5.06), and total symptom score by 6.89 points (95% CI, -8.02 to -5.76).

In the nasal polyp clinical studies, about 60% of patients with nasal polyps are diagnosed with asthma, Dr. Han said. However, the inflammatory endotype of asthma and nasal polyps suggests a higher prevalence for nasal polyps.

“Unless you do a nasal endoscopy, you’re not seeing the nasal polyps,” he said. “And sometimes nasal polyps are just in the sinus cavities, and you don’t see them until they come outside the sinus cavities. That’s why I think nasal polyps are likely underdiagnosed.”

Clinicians are starting to recognize the need to assess asthma in patients with chronic sinusitis. They should assess for sinusitis and nasal polyps in patients with asthma as well. The coassociation with chronic sinusitis or nasal polyps may be less recognized in patients with asthma.

“As soon as you see asthma, you have to think of chronic sinusitis and possibly nasal polyps,” Dr. Han said. “If a patient has asthma and loses their sense of smell, you have to think of nasal polyps. And for patients who present with chronic sinusitis, you have to think of asthma.”