FDA starts review of AZ's COPD blockbuster hope

The FDA has started a priority review of AstraZeneca's IL-33-targeting antibody tozorakimab for chronic obstructive pulmonary disease (COPD), setting up a decision on the would-be blockbuster in the first quarter of 2027.

It's an indicator of AZ's excitement about tozorakimab that it is spending a priority review voucher – typically worth between $100 and $200 million on the open market – to ensure that tozorakimab proceeds through the FDA's appraisal as quickly as possible.

The filing is based mainly on the phase 3 OBERON and TITANIA trials, which showed that a once-monthly, 300 mg subcutaneous dose of the antibody was able to significantly reduce moderate and severe COPD exacerbations – the debilitating attacks that signal progression of the disease and are associated with an increased risk of hospitalisation and death.

News of the FDA's review came as the results of OBERON and TITANIA were published in the New England Journal of Medicine and presented at the European Respiratory Society (ERS) congress in Barcelona, Spain.

In OBERON, tozorakimab achieved a 30% relative reduction in exacerbations compared to placebo when added to standard inhaled care, while in TITANIA the reduction came in at 29%. Looking only at subjects who were former smokers, the reductions came in at 29% and 34%, respectively.

The two studies spanned a broad range of COPD patients, including former and current smokers and people with a broad range of lung functions and levels of inflammatory eosinophil cells.

The eosinophil observation is particularly important, as the current biologics for COPD, Sanofi/Regeneron's IL-4 and IL-13 inhibitor Dupixent (dupilumab) and GSK's anti-IL-5 antibody Nucala (mepolizumab), are only labelled for use in patients with elevated counts.

Also at ERS, AZ presented results from an integrated analysis of OBERON and TITANIA that demonstrated a reduction in patients' mucus plug score – a biomarker linked to worse outcomes in COPD. It said tozorakimab is the first biologic to reduce mucus plugging in a broad population of COPD patients.

AZ announced topline results of the studies earlier this year, along with data from a third study, MIRANDA, which compared a two-weekly dose of tozorakimab to placebo in COPD patients still experiencing moderate-to-severe exacerbations while on inhaled standard of care.

The three studies put AZ firmly in the lead to bring an anti-IL-33 drug to market for COPD, after some other highly anticipated drug candidates – such as Sanofi/Regeneron's itepekimab and Roche's astegolimab – generated mixed results in clinical trials.

The company has said it believes peak sales of tozorakimab could eventually reach multibillion-dollar levels – perhaps $3 to $5 billion – if it gets approved with a broad label in COPD.

Sharon Barr, AZ's head of biopharma R&D, said the OBERON and TITANIA data "set a new standard for COPD treatment outcomes in a broad population of patients" and back up tozorakimab's proposed mechanism of decreasing inflammation and disrupting the cycle of mucus dysfunction.

Tozorakimab is also under review in the EU and China, and is in a phase 3 trial in severe viral lower respiratory tract disease and a phase 2 trial in patients with severe asthma.

Image by Engin Akyurt from Pixabay