Setback for AZ as tralokinumab flunks asthma trial

AstraZeneca’s hopes of bringing severe asthma candidate tralokinumab to market look rocky after it failed two phase III trials.

Tralokinumab was unable to reduce the annual exacerbation rate in patients with severe, uncontrolled asthma and elevated levels of a biomarker (Fractional exhaled Nitric Oxide or FeNO) compared to placebo in the STRATOS 2 study. And in the TROPOS trial it was unable to achieve a significant reduction in oral corticosteroid use when added to standard care.

The twin misses look like they spell the end for the programme in asthma, which AZ chief medical officer Sean Bohen said was “a complex disease with limited treatment options today”.

It’s a blow to the UK big pharma company’s ambitions in respiratory medicine, and makes it more important that AZ’s other late-stage severe asthma candidate benralizumab achieves its potential. Tralokinumab is an inhibitor of interleukin-13 (IL-13), while benralizumab works by blocking the activity of IL-5.

The latter drug is under regulatory review in the US, EU, Japan and other countries, with an FDA verdict due before the end of the year.

The failure of tralokinumab hasn’t come out of the blue, as another trial (STRATOS 1) also failed to hit the mark, and other IL-13 inhibitors - including Roche’s lebrikizumab and Pfizer’s anrukinzumab - disappointed in asthma.

At one point, tralokinumab and benralizumab were tipped to become a $1.8bn duo by analysts, but now tralokinumab’s future is in doubt and benralizumab is chasing a third-to-market position behind GlaxoSmithKline's Nucala (mepolizumab) and Teva's Cinqaero (reslizumab).

Last year AZ's respiratory pipeline suffered another setback after the company halted a phase IIa trial of a Synairgen-partnered inhaled interferon beta formulation (AZD9412) for asthma, deciding it was unlikely to give conclusive results.

Asthma affects 315m individuals worldwide, and up to 10% of asthma patients have severe asthma, which may be uncontrolled despite high doses of bronchodilator and anti-inflammatory medicines including chronic steroids.