Competing to treat patients with severe eosinophilic asthma (SEA), AstraZeneca has fared well matching its IL-5 inhibitor Fasenra up against GSK’s Nucala.
But AZ has stumbled in its efforts to add indications to Fasenra's label. In 2022, the FDA rejected the medicine to treat rhinosinusitis. Then, later in the year, shaky trial data derailed the company’s bid for an approval in eosinophilic esophagitis (EoE).
On Monday, however, the company revealed positive news for Fasenra as it has achieved its primary endpoint in the phase 3 MANDARA trial, demonstrating noninferior rates of remission in a head-to-head battle against Nucala in patients with eosinophilic granulomatosis with polyangiitis (EGPA).
AZ did not provide numbers with the trial results. Those will come at a future medical conference, the company said.
With a 2017 label expansion, Nucala is the only treatment approved for EGPA. In proving noninferiority to Nucala, AZ's Fasenra did so with a smaller dosing regimen—one 30-mg subcutaneous injection every four weeks versus three 100-mg injections of Nucala over the same period.
While the dosing edge is one positive for AZ's drug, remission is the primary focus for the company.
“Our goal is to make remission a treatment goal for every patient with severe asthma and with EGPA,” Andrew Menzies-Gow, AZ’s global medical head of respiratory biologics, said in an interview. “We feel that’s a goal that will dramatically shift how patients are treated today.”
Asthma patients typically take on additional treatments as the severity of their disease increases, Menzies-Gow said. But with Fasenra’s ability to control disease, patients can be weaned off the added therapies.
This week at the European Respiratory Society (ERS) International Congress in Milan, AZ is presenting evidence from the SHAMAL phase 4 trial showing that Fasenra allows for reduction in background treatment. Of the 168 SEA patients in the trial’s tapering arm, 92% maintained disease control and remained exacerbation-free despite a decrease in inhaled corticosteroid therapy.
Also at the ERS meeting, AZ presented data that showed Fasenra’s ability to sustain remission. In the BORA phase 3 extension study, of the nearly 1 in 3 SEA patients who achieved remission through 12 months of treatment, 73% remained so for another 12 months.
“This concept of remission is particularly central across our biologics portfolio, across a number of diseases,” Pablo Panella, AZ’s senior vice president, global respiratory, said in the interview. “We believe that this can have a profound impact in increasing the access to biologics in the class as a whole.”
In coming up short in a trial of EoE patients last year, Fasenra cleared the remission bar, topping placebo. But it failed to meet its other objective, which was to relieve swallowing issues (dysphagia) that come with the disorder.
As for EGPA, which was formerly known as Churg-Strauss syndrome, the condition is a rare immune-mediated vasculitis that can damage the lungs, heart, skin, nerves and gastrointestinal system. It is potentially fatal and affects roughly 118,000 people worldwide.
Fasenra binds to the IL-5 receptor alpha, directly targeting the eosinophils. Published evidence suggests there is a "very rapid and near depletion of both blood and tissue eosinophils as a result of this mechanism of action," Menzies-Gow said. The drug won its original approval in SEA back in 2017.
It didn’t take Fasenra long to achieve blockbuster status, as the drug generated sales of $1.26 billion in 2021. But sustaining the growth rate has been difficult without gaining another indication. Last year, Fasenra sales increased (PDF) by 11% to $1.4 billion, compared to $1.86 billion for Nucala.