AstraZeneca and Amgen’s tezepelumab has missed (PDF) the primary endpoint in a phase 2a atopic dermatitis trial. The midphase misstep raises doubts about the prospects of the thymic stromal lymphopoietin antagonist making a mark in a congested field featuring Sanofi, Pfizer and Novartis.
Tezepelumab was last seen acing an asthma phase 2b with data that dialed up expectations in the indication. The monoclonal antibody fared worse in the atopic dermatitis phase 2a.
Investigators enrolled 155 adults with moderate-to-severe atopic dermatitis and randomized them to receive twice-monthly subcutaneous injections of tezepelumab or placebo on top of medium to high strength glucocorticosteroids.
Tezepelumab failed to statistically outperform placebo against the Eczema Area and Severity Index over the course of the 12-week trial, although AstraZeneca saw a numeric improvement in the treatment arm. That resulted in the study missing its primary endpoint. AstraZeneca also saw numeric improvements against secondary endpoints that tracked tezepelumab’s performance against the Investigator's Global Assessment score and Scoring of Atopic Dermatitis scale.
The drug is one of five monoclonal antibodies covered by the deal AstraZeneca struck with Amgen in 2012. That deal saw AstraZeneca pay $50 million upfront to gain a stake in five drugs in Amgen’s clinical inflammation pipeline. Since then, the partners have split the costs of development and AstraZeneca has led the strategy for some of the assets, including tezepelumab.
AstraZeneca and Amgen now face the task of assessing whether the numeric, but not statistical, differences in favor of tezepelumab seen in the atopic dermatitis trial justify further development.
One argument against forging ahead with tezepelumab stems from the level of competition for the atopic dermatitis market. The FDA approved Regeneron and Sanofi’s IL-4-IL-13 inhibitor dupilumab in moderate-to-severe atopic dermatitis in March following a clinical trial program that cleared efficacy bars with ease. And with Pfizer looking to corner the mild-to-moderate end of the market with Eucrisa and the likes of Leo Pharma and Novartis giving chase, the field is congested.
Tezepelumab could face off against some of the same drugs in the asthma market. Regeneron and Sanofi are also developing dupilumab—brand name Dupixent—in uncontrolled asthma. Novartis is also developing CRTH2 antagonist fevipiprant in asthma and atopic dermatitis.
Having impressed with phase 2b data earlier this year, tezepelumab looks to be on firmer footing in asthma, although again it will face fierce competition.