PHILADELPHIA — The investigational drug verekitug improved sinonasal symptoms, reduced nasal polyp size, and reduced the need for nasal polyp surgery in people with chronic rhinosinusitis with nasal polyps, according to a phase 2 trial presented at the American Academy of Allergy, Asthma and Immunology (AAAAI) 2026 Annual Meeting in Philadelphia.

“Verekitug led to significant improvements in nasal congestion score as early as week 2 [and] was well tolerated with no serious adverse events,” reported Joseph K. Han, MD, chief of the Division of Allergy and a professor of otolaryngology at Old Dominion University in Norfolk, Virginia, and his colleagues.

Chronic rhinosinusitis with nasal polyps involves sinonasal inflammation and loss of smell. The thymic stromal lymphopoietin (TSLP) signaling pathway triggers a type 2 inflammatory response and is therefore a driver of the immune activation that causes chronic rhinosinusitis morbidity, the authors explain. Verekitug, previously known as UPB-101 and ASP7266, is an investigational monoclonal antibody that targets the TSLP receptor.

Preclinical research showed that verekitug more effectively suppressed TSLP-driven responses than the anti-TSLP antibody tezepelumab, the authors wrote. A subsequent phase 1 trial showed that verekitug caused sustained reductions in blood eosinophil levels and fractional exhaled nitric oxide for up to 24 weeks in participants with asthma.

The phase 2 double-blind, randomized controlled VIBRANT trial enrolled 81 adults with chronic rhinosinusitis with nasal polyps who had a history of nasal polyp surgery or nasal polyp exacerbation requiring systemic corticosteroids within the previous 2 years. They all had a nasal polyp score of at least 5 (0-8), had a nasal congestion score of at least 2 over 14 days (0-3), had symptoms for at least 8 weeks, and had been receiving a stable standard of care treatment for at least 30 days.

The participants had a median age of 50 years, and 64% were men. They had a mean blood eosinophil count of 449 cells/μL and a mean nasal polyp score of 6.01. More than half (64%) had a history of surgery for chronic rhinosinusitis with nasal polyps, 42% had a history of systemic corticosteroids, and 58% had a history of comorbid asthma or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease.

A total of 41 participants received 100 mg of subcutaneous verekitug, while 40 received a placebo, administered every 12 weeks for 24 weeks. Participants receiving verekitug experienced a 2.05-point reduction in their nasal polyp score from baseline at 24 weeks compared with a 0.28-point reduction in the placebo group, yielding a least-squares mean (LSM) difference of 1.77 points (P < .0001). In a secondary efficacy endpoint analysis using a worst-observation-carried-forward approach — accounting for use of rescue nasal polyp surgery or systemic corticosteroids, or escalation of maintenance treatment for the chronic rhinosinusitis with nasal polyps — the change in baseline was -1.97 in the verekitug group and -0.02 in the placebo group (LSM, -1.95; P < .0001).

Verekitug also showed improvements in secondary endpoints, including a significant reduction in nasal congestion score at 24 weeks for those receiving the drug compared with those receiving placebo (LSM, -0.77; P = .0003). The need for surgery or systemic corticosteroids was 76% lower (odds ratio [OR], 0.24; P = .03) in those who received verekitug (n = 3) than in those receiving placebo (n = 10).

The LSM change in baseline for the total symptom score was 4.69 points lower in the verekitug group than the placebo group (P = .001), and the LSM difference in difficulty with sense of smell was 0.85 points better with verekitug than placebo (P = .0002). The LSM difference in Lund-Mackay score was 8.07 points lower with verekitug than with placebo. 

Safety outcomes showed that treatment-emergent and treatment-related adverse events occurred more often with placebo than with verekitug. About two thirds of participants experienced any treatment-emergent adverse event in both the verekitug (67.5%) and placebo (65%) groups, but three of these were related to the study treatment in the placebo group compared with one in the verekitug group. Five events in the placebo group and two in the verekitug group were at least grade 3, but no serious adverse events occurred in either group.

Martin Desrosiers, MD, ear, nose, and throat surgeon, researcher, and clinical professor at McGill University in Montreal, Canada, and president of Probionase Therapies, Inc., was not involved in the trial but told Medscape Medical News he was impressed with the results.

“What strikes me from the VIBRANT trial is it articulates two things,” Desrosiers said. “One is that the TSLP remains a good target because it shows that you get a powerful result, which is comparable to other market leaders with an effective safety profile, with three monthly doses. So, in theory, the medication presents advantages.”

Further, he added, “It also suggests that the TSLP receptor strategy might work as well. Certainly, this opens up the field towards a new era of categories for strengths of medication,” fulfilling an unmet need while offering a powerful agent that complements existing alternatives. “It’s not more powerful than what exists, but it’s as powerful as the powerful ones, giving physicians options to select with the individualized patient,” Desrosiers said. “Obviously, more needs to be done to understand who’s the ideal patient, but certainly it's very exciting and promising, and it's certainly worthy of developing further.”

The research was funded by Upstream Bio, Inc. Han reported receiving consulting fees and honoraria from GSK, Sanofi, Regeneron, and AstraZeneca, and various other authors reported disclosures involving a range of industry companies. Six coauthors are employees and stockholders of Upstream Bio, Inc., and a seventh coauthor was an employee at the time of the study. Three authors had no disclosures. Desrosiers is the president of Probionase Therapies, Inc., which makes probiotics for the nose, has received industry funding from GSK and Sanofi, and is a consultant for AstraZeneca.

Tara Haelle is a science/health journalist based in Dallas.