AstraZeneca’s Fasenra is already late to the game in nasal polyps, and now the drug is being pushed back even further—if it can eventually get there.
The FDA has rejected AstraZeneca’s bid to expand Fasenra into chronic rhinosinusitis with nasal polyps, the British pharma said Monday. The agency is asking for additional clinical trial data, and AZ said it’s working closely with the regulator on potential next moves.
The complete response letter puts Fasenra at a disadvantage in the competition among anti-inflammatory biologics. Last summer, GlaxoSmithKline’s rival IL-5 inhibitor Nucala earned an FDA go-ahead in the field, following Sanofi and Regeneron’s IL-4/13 antibody Dupixent into the ring.
For its part, AZ believed Fasenra had what it took to win an approval based on data from the phase 3 OSTRO trial. In patients with chronic rhinosinusitis with nasal polyps who remained symptomatic despite standard therapy, Fasenra topped placebo at reducing nasal polyp burden and patient-reported nasal obstruction.
AZ is already running a separate phase 3 trial, dubbed ORCHID, for Fasenra in nasal polyps. The newer trial also uses improvements in nasal polyp burden and nasal blockage as the co-primary endpoints. But unlike OSTRO, ORCHID is evaluating Fasenra’s performance longer at 56 weeks versus 40 weeks for OSTRO in the primary outcomes measurement. Plus, while OSTRO enrolled a group of nasal polyps patients regardless of blood count of eosinophil—a type of white blood cell that indicates inflammation—ORCHID only allows patients with eosinophilic disease with a minimum eosinophil level.
It’s not immediately clear whether ORCHID could satisfy the FDA’s data requirements. And, even if it does, the trial won’t read out until September 2023, according to ClinicalTrials.gov, which means a potential FDA nod based on a resubmission will be two years out from now.
Fasenra is currently allowed in eosinophilic asthma. The drug crossed the blockbuster threshold last year, delivering sales of $1.26 billion, up 31% year over year.
Nucala, Fasenra’s in-class rival, chalked up a smaller 22% growth at constant exchange rates, reaching 1.14 billion pounds sterling ($1.49 billion) in 2021. The GSK drug bears a broader label. Besides asthma and nasal polyps, Nucala is also approved for other eosinophilic diseases including hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA).
AZ is looking at a busy couple of years for Fasenra data reporting. The phase 3 NATRON trial in HES and the phase 3 MESSINA study in eosinophilic esophagitis could provide data in the second half this year, and results from the phase 3 MANDARA trial in EGPA are expected in 2023.