Tezepelumab

Based on the latest nasal polyps results, Leerink Partners analysts stood by their $4.3 billion Tezspire sales projection for Amgen by 2030. Already billed as a potential blockbuster, Amgen and AstraZeneca’s Tezspire has turned in strong clinical data in chronic rhinosinusitis with nasal polyps (CRSwNP). Tezspire showed numerically better efficacy results in CRSwNP compared with two prominent rivals in the three drugs' separate studies. However, separate teams of analysts at William Blair and Leerink Partners stopped short of handing Tezspire the crown in the indication, citing trial design differences that likely play into the cross-trial comparisons.As Amgen and AZ previously announced, Tezspire significantly improved total nasal polyp score (NPS) and nasal congestion score (NCS) in patients with CRSwNP compared with placebo after 52 weeks in the phase 3 Waypoint study.On NPS, a metric with a range of 0 to 8, treatment with Tezspire led to a placebo-adjusted average improvement of nearly 2.07 points, according to results presented at the joint conference of the American Academy of Allergy, Asthma & Immunology and the World Allergy Organization. On NCS, which is scored between 0 and 3, Tezspire performed about 1.03 points better than placebo.The drug also nearly eliminated the need for future surgery and corticosteroid use, Joseph Han, M.D., from the Eastern Virginia Medical School and a co-primary investigator of the Waypoint trial, highlighted in a statement Saturday.Tezspire, which is already approved in severe asthma, didn’t raise any new safety signals, according to investigators. Serious adverse events occurred in 4.9% of Tezspire patients, versus 5.9% in the placebo group.Tezspire’s efficacy numbers came in slightly above Dupixent’s figures from two of its own phase 3 trials, Sinus-24 and Sinus-52. Results from those studies in 2019 enabled the Sanofi and Regeneron antibody to become the first treatment approved by the FDA in inadequately controlled CRSwNP. Dupixent’s 52-week placebo-adjusted difference was 1.8 on NPS and 0.9 on NCS.What’s more, the Tezspire data also look better than results for GSK’s depemokimab. In the phase 3 Anchor-1 and Anchor-2 trials, depemokimab’s 52-week NPS difference amounted to 0.7 points versus placebo. Rather than NCS, the GSK trials used a different co-primary endpoint called verbal response scale to measure nasal obstruction.Based on the results, the Leerink team stood by its $4.3 billion Tezspire sales projection for Amgen by 2030, compared with the consensus estimate of $3 billion. CRSwNP is marked by persistent inflammation of the nasal mucosa, accompanied by nasal polyps, which can block the nose. The inflammatory disease represents a big market, as Dupixent has already achieved blockbuster annual sales in the indication alone, Marion McCourt, commercial chief at Regeneron, said during a conference call last month.The three biologics work in different ways. Tezspire blocks thymic stromal lymphopoietin (TSLP), while depemokimab targets IL-5 and Dupixent inhibits the IL-4/13 axis.“With its first-in-class mode of action, targeting TSLP at the top of the inflammatory cascade, the data add to the body of evidence that [Tezspire] can transform care for patients with epithelial-driven inflammatory diseases,” Sharon Barr, AZ’s head of biopharmaceuticals R&D, said in a statement Saturday.The William Blair analysts said the results “hint at best-in-disease therapy." Importantly, though, both sets of analysis said trial design differences may have impacted the drugs’ relative trial performances.Flagging several nuances in enrollment criteria, Leerink analysts suggested that compared with the Dupixent trials, “Tezspire enrolled a more selective group regarding respiratory comorbidities, but a broader population in terms of prior surgery.”To enroll in Tezspire’s Waypoint trial, patients were required to meet certain bars on NCS and the sino-nasal outcome test (SNOT-22), which measures the symptoms and consequences of rhinosinusitis. GSK’s Anchor trials, which didn’t implement such restrictions, enrolled a “somewhat milder population,” the William Blair team noted.Among the three agents, GSK’s depemokimab appears to have the weakest efficacy numbers—not just on the co-primary endpoint of NPS but also on some secondary endpoints such as change in SNOT-22 score. However, William Blair analysts suggested that the drug’s efficacy may be underestimated given the differences in trial populations.As a twice-yearly therapy, depemokimab boasts a long-acting advantage. Tezspire is dosed subcutaneously every month, while Dupixent is given every other week.“As highlighted by the presenter, patient preference shifts to an injectable therapy over daily orals when the treatment interval is as infrequent as every six months, which could lead to modest commercial uptake in some patients if approved,” William Blair analysts said in a Monday note. Han presented both datasets for Tezspire and depemokimab at AAAAI. During the Q&A session, Han recommended that future trials in CRSwNP incorporate baseline thresholds such as SNOT-22 to focus on moderate-to-severe patients, rather than milder patients who were also allowed in GSK’s Anchor studies, according to William Blair.TSLP as a target has lately attracted much interest, partly thanks to the success of Tezspire. Continuing with its long-acting pursuit, GSK last year bought Aiolos Bio and its anti-TSLP candidate, AIO-001, which the British pharma believes may be dosed once every six months. The candidate was originally licensed from China’s Jiangsu Henguri Pharmaceuticals.Also gunning for a twice-yearly anti-TSLP antibody, Windward Bio emerged earlier this year with a $200 million series A led by OrbiMed, Novo Holdings and Blue Owl Healthcare Opportunities, plus a clinical candidate licensed from China’s Kelun-Biotech and Harbour BioMed.Johnson & Johnson’s $850 million acquisition of Proteologix last year also featured an IL-13/TSLP bispecific. And Upstream Bio could report phase 2 CRSwNP data for verekitug, an antibody targeting the TSLP receptor, later this year.