FDA Approves Tezspire as First Biologic Targeting TSLP for Chronic Rhinosinusitis With Nasal Polyps

The FDA has approved Tezspire (tezepelumab-ekko; Amgen and AstraZeneca) as an add-on maintenance therapy for patients 12 years of age and older with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP). The regulatory action makes Tezspire the first and only biologic for CRSwNP that targets thymic stromal lymphopoietin (TSLP).¹

Tezspire expands its respiratory indications with new FDA approval

“For people living with CRSwNP, every breath can feel like a struggle, and many endure years of recurring symptoms and surgeries without significant relief. The approval of Tezspire represents a meaningful advance, derived from our longstanding focus on complex inflammatory diseases rooted in epithelial biology,” Jay Bradner, MD, executive vice president of Research and Development at Amgen, said in a press release. “This approval is an important step forward for patients who have long needed more durable options that address the root causes of this disease, while establishing the impact of TSLP inhibition beyond asthma.”¹

• Tezspire, a first-in-class human monoclonal antibody, acts on the airway epithelium, which is the primary cause of inflammation and the first point of contact for viruses, allergens, pollutants, and other environmental irritants.
• The drug inhibits TSLP, an alarmin-class cytokine that acts in the early stages of the inflammatory process.
• The expression of TSLP is elevated in the airways of patients with asthma and is associated with disease severity.
• Tezspire was initially approved in December 2021 as the only biologic indicated for severe asthma with no phenotype or biomarker limitation within its approved label.
• In February 2023, Tezspire was approved as a pre-filled, single-use pen for patients aged 12 years and older with severe asthma.²

Understanding chronic rhinosinusitis with nasal polyps

• CRSwNP is an inflammatory disorder involving persistent inflammation of the nasal mucosa along with nasal polyps.
• These polyps may block nasal passages, causing breathing issues, loss of or limited sense of smell, nasal discharge, facial pain, sleep disruption, and other adverse effects that inhibit quality of life.
• The inflammatory disease affects an estimated 320 million people worldwide and often persists despite standard corticosteroid treatments and repeated sinus surgeries.

“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,” Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America, said in the release.

“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.”¹

WAYPOINT Phase III trial design and endpoints

• The latest approval of Tezspire was based on findings from the Phase III WAYPOINT trial (NCT04851964).
• The double-blind, multi-center, randomized, placebo-controlled, parallel-group WAYPOINT trial analyzed the efficacy and safety of Tezspire in adults with severe CRSwNP compared with placebo administered as a subcutaneous injection.
• Patients who successfully completed the 52-week treatment regimen were eligible for the post-treatment follow-up period of 12–24 weeks.
• The trial’s co-primary endpoints were change in total nasal polyp size from baseline as per endoscopic total Nasal Polyp Score and change in biweekly mean nasal congestion from baseline as per participant-reported Nasal Congestion Score analyzed as part of the daily Nasal Polyposis Symptom Diary.
• The trial’s key secondary endpoints included loss of smell; improvement in disease-specific health-related QoL as per SinoNasal Outcome Test score; Lund-Mackay score; time to surgery decision and/or systemic corticosteroids for nasal polyposis; time to nasal polyposis surgery decision; time to systemic corticosteroids for nasal polyposis; Nasal Polyposis Symptom Diary total symptom score; and pre-bronchodilator FEV1 in trial participants with comorbid asthma and aspirin-exacerbated respiratory disease/non-steroidal anti-inflammatory-exacerbated respiratory disease at 52 weeks.

Key results: reduced polyp burden, surgeries, and steroid use

• The results showed Tezspire produced a statistically significant and clinically meaningful decrease in the severity of nasal polyps.
• Further, the drug nearly removed the need for surgery and significantly lowered use of systemic corticosteroids compared to placebo.

Expert perspectives on patient impact

“Over 320 million lives globally are disrupted by chronic rhinosinusitis with nasal polyps. The FDA approval of Tezspire brings forward a new treatment option that has demonstrated rapid and sustained symptom improvement, nearly eliminating the need for future surgeries and significantly reducing systemic steroid use,” WAYPOINT trial co-primary investigator Joseph Han, MD, FARS, FAAOA, vice chair of Department of Otolaryngology, Head and Neck Surgery, Old Dominion University, said in the release. “By targeting (TSLP) at the top of the inflammatory cascade, Tezspire offers a novel option for patients who continue to endure the disruption of this disease despite available treatments.”¹