Since GSK’s Nucala and AstraZeneca’s Fasenra were approved two years apart to treat patients with severe asthma, the IL-5 inhibitors have engaged in a spirited market battle, with one key difference: While Nucala has added three indications since its original FDA nod in 2015, Fasenra has been shut out in its attempts to expand to new diseases.
That changed on Tuesday however, as the FDA signed off on Fasenra for patients with eosinophilic granulomatosis with polyangiitis (EGPA), a rare, immune-mediated vascular disorder that can damage various organs and can be fatal if left untreated.
Nucala is the only other drug approved in the indication. GSK gained that nod from the FDA in 2017. Fasenra won over the U.S. regulator by showing non-inferiority to Nucala in the phase 3 MANDARA study in 140 patients with relapsed or refractory EPGA.
On establishing non-inferiority on the trial’s primary objective, Fasenra helped 59% of patients achieve remission at both weeks 36 and 48, compared with 57% for Nucala, according to Fasenra’s updated FDA label. Some other key metrics favored AZ’s medicine. For example, 41% of those who took Fasenra were able to eliminate steroids from their treatment regimen, compared to 26% of those on Nucala.
“What’s key is that this was the first head-to-head study of biologics ever,” Donna Carstens, M.D., AZ’s senior medical director, respiratory, said in an interview. “In a clinical trial of this, albeit smaller magnitude but a disease state that’s rare and has an umbrella effect on severe eosinophilic asthma, it’s huge.”
Another key difference in the study was the dosing. While patients on Fasenra received one 30-mg subcutaneous injection every four weeks, those on Nucala took three 100-mg injections once every four weeks.
Carstens explained how drugs from the same treatment class can have such different dosing requirements.
“Our mechanism of action is indeed different to that of [Nucala]. They block the cytokine, we actually eliminate the eosinophils,” Carstens said. “We know with a 30-mg dose from a pharmacodynamics standpoint, that we get very efficient reduction in eosinophil counts, which are the main inflammatory cell in this disease.”
EGPA, which was formerly known as Churg-Strauss syndrome, affects roughly 118,000 people worldwide and can often be undetected.
“Ninety-five percent of the cases present with severe asthma and sinus disease and nasal polyps. So, if you’re not looking beyond managing the asthma then you may miss this,” Carstens said. “The eosinophils are typically much higher than you would see in someone with severe eosinophilic asthma. So, it’s important to have that recognition that this is something else because of the potential significant multi-organ dysfunction and impact.”
Fasenra was approved in 2017 but AZ came up short in its attempts to expand its label to chronic obstructive pulmonary disorder (COPD), rhinosinusitis and eosinophilic esophagitis, where it cleared the remission bar in a trial but failed to meet its other objective, which was to relieve swallowing issues called dysphagia.
Meanwhile, in addition to its approvals to treat severe asthma and EGPA, Nucala gained nods from the FDA to treat hypereosinophilic syndrome (HES) in 2020 and rhinosinusitis in 2021.
Fasenra still has held its own in the market, with sales (PDF) reaching $1.6 billion, which was an increase of 12% from 2022. Meanwhile, GSK reported sales (PDF) of Nucala at £1.655 ($2.2 billion) for 2023 which was an increase of 18% year over year.