A first-in-class therapy developed by AstraZeneca and Amgen looks like a strong treatment candidate for severe uncontrolled asthma, according to a respiratory specialist.

In the phase 2b PATHWAY trial, tezepelumab (AMG-157)—a first-in-class thymic stromal lymphopoietin (TSLP) antagonist—achieved a 61% to 71% reduction in the annual rate of asthma attacks depending on dose, which analysts at Jefferies say is on the higher end of the 50% to 70% efficacy range seen with competing therapies. The data was published in the New England Journal of Medicine and will be presented at the European Respiratory Society (ERS) meeting next week.

Tezepelumab was given as an add-on therapy to patients whose asthma was uncontrolled despite the use of steroid and bronchodilator drugs, a group which accounts for around 15% of all asthma sufferers, according to professor of pulmonary disease at the University of Amsterdam and ERS president Elisabeth Bel, M.D., Ph.D. In an editorial accompanying the NEJM report, she describes tezepelumab as potentially "the broadest and most promising biologic" for uncontrolled asthma to date.

If it makes it through development, tezepelumab will enter a market currently being transformed by targeted therapies such as Sanofi and Regeneron's IL-4 and IL-14 inhibitor Dupixent (dupilumab) and GlaxoSmithKline's Nucala (mepolizumab).

TSLP is an attractive target in asthma, as it may allow the inflammatory cascade mechanism to be shut down further upstream than other targeted therapies, according to Jefferies' analysts, who note that the trial reveals "important broad reduction of key biomarkers that may suggest differentiation [and] which suggest a broad and 'upstream' approach to shutting down the inflammatory pathway perhaps more broadly than other drugs."

That potential could however go hand-in-hand with potential side effects such as infections, which will have to be monitored closely in phase 3, they add, but based on the profile revealed in the study they suggest tezepelumab "could be a new potential blockbuster waiting in the wings."

Lead PATHWAY investigator Jonathan Corren, M.D., of the David Geffen School of Medicine at UCLA said in a release that tezepilumab's early action in the inflammatory cascade could make it "suitable for patients with both [type] 2 and non-[type] 2 driven asthma, including those ineligible for current biologic therapies which only target the type 2 pathway."

Meanwhile, Leerink analyst Seamus Fernandez suggests that could happen very soon if AZ and Amgen can persuade the FDA to approve the drug on the strength of the phase 2b data while they carry out a confirmatory phase 3 trial, an approach that Regeneron and Sanofi are trying with Dupixent.

If all goes according to plan, the drug could reach sales of $4.5 billion within the next five years—which would go a long way to softening the blow AZ recently suffered when its immuno-oncology combination of Imfinzi (durvalumab) and tremelimumab failed to hit the mark in the MYSTIC trial.

Amgen and AZ partnered on the drug five years ago as part of a joint venture intended to draw on each other's strengths. Amgen will be eligible for profit-share payments in the future if tezepelumab reaches the market, with AZ taking the commercial lead on the project.