Since late 2017, AstraZeneca’s Fasenra has been allowed as an add-on treatment to help reduce asthma patients’ episodes of sudden symptom worsening. And new data now show that the drug can spare patients the use of steroids, an important component of their disease maintenance regimen.
In a single-arm phase 3b trial, Fasenra helped 62% of nearly 600 patients with severe asthma to go on about their lives without oral corticosteroids, AstraZeneca said Thursday. More patients, or 81%, had their daily steroid dose reduced to 5mg or below, including those who stopped use completely.
Steroids are a common base drug that Fasenra is usually added on top of. “However, over-reliance on oral corticosteroids can also cause significant health risks for patients, as well as additional strain on health systems,” Mene Pangalos, AZ’s BioPharmaceuticals R&D chief, said in a statement. “These data further support Fasenra’s clinical profile in eliminating oral corticosteroid use across a broader population of severe asthma patients.”
The FDA based Fasenra’s 2017 approval on data from three phase 3 trials, including Sirocco and Calima, which showed the drug, as an add-on maintenance treatment, reduced patients' annual flare-up rate over placebo and improved lung function as measured by forced exhaling volume in one second.
The third trial, dubbed Zonda, demonstrated that Fasenra significantly reduced the median final oral steroid doses from baseline by 75%, as compared with a reduction of 25% for placebo, all the while reducing patients’ annual exacerbation rate to levels lower than that of placebo. In that trial, more than half of Fasenra patients were not receiving steroids at all in the end, as compared with 19% for the placebo group.
Meanwhile, Fasenra’s archrival, GlaxoSmithKline’s Nucala, also has its own steroid-sparing data to tout. In the Sirius trial, Nucala achieved a 50% median reduction from baseline in steroid use, as compared with no change in the placebo group. Overall, 23% of Nucala patients experienced a greater than 90% reduction in steroid dose, versus 11% for those on placebo.
But AstraZeneca argues that the new Fasenra trial, called Ponente, holds unique significance in that it has a longer maintenance phase of about 24 weeks to 32 weeks. In comparison, in AZ’s Zonda and GSK’s Sirius, the maintenance periods—in which steroid use was kept unchanged after the induction and reduction phases—were both four weeks. This means that Fasenra now has data showing more durable steroid elimination or reduction than was shown in previous trials.
Chronic steroid use can also impede the normal function of adrenal glands, potentially causing adrenal insufficiency, a serious condition where the body can’t make enough hormones that are essential for body functions. The condition can happen even as the steroid dose is being reduced.
Ponente introduced a personalized steroid tapering schedule during the reduction phase, whereas the other trials were prespecified. That design was particularly important “because adrenal insufficiency can be a barrier to safe and meaningful oral corticosteroid reduction,” Andrew Menzies-Gow, principal investigator of the Ponente trial, said in a statement. “These data should inform severe asthma treatment guidelines and strengthen physicians’ confidence to more safely eliminate chronic oral corticosteroid use in their patients.”
The competition among biologics within the inflammatory respiratory disease space is getting more intense. Fasenra is eyeing an FDA nod in chronic rhinosinusitis with nasal polyps, chasing Nucala and Sanofi and Regeneron’s Dupixent. Nucala also recently snagged a new FDA green light in hypereosinophilic syndrome, a rare condition marked by overproduction of the white blood cell eosinophils. Fasenra has posted similar data in the disease.