In two Phase III trials, investigators say, the mega-blockbuster hopeful delivered a clean sweep over chronic rhinosinusitis with nasal polyps, clearing obstruction and shrinking abnormal tissue growth at a much higher rate than placebo.
The “incrementally positive” results, as Baird analyst Brian Skorney puts it, come days ahead of an expected regulatory decision on the moderate-to-severe asthma application, which Sanofi and Regeneron sent in after Dupixent hit key endpoints in a Phase III a year ago.
While analysts were more skeptical of the drug’s commercial potential in asthma due to competition from both existing (GSK’s Nucala) and upcoming rivals (tezepelumab from AstraZeneca and Amgen), in this case Skorney is more interested in the fact that Dupixent beat the current standard of care — oft-ineffective corticosteroid followed by expensive surgery.
Dupixent’s demonstrated ability to significantly reduce symptoms in a heavily pre-treated patient population in which more than half of the patients had previously undergone surgery, and nearly 75% had used corticosteroids, should drive strong commercial uptake in this indication where there remains a significant unmet need.
SINUS-24 and SINUS-52 enrolled 276 and 448 patients, respectively. At 24 weeks, patients in the two trials who received a combo of Dupixent and corticosteroid nasal spray experienced a 51% and 57% improvement in nasal congestion/obstruction severity, versus 15% and 19% in the two placebo (plus nasal spray) arms. In the drug arms, patients’ nasal polyps score — which measures the size of their polyps — shrunk by an average of 27% and 33%, while those on placebo saw 4% to 7% increases.
Those are the co-primary endpoints, with p < 0.0001; the partners say Dupixent also scored on key secondary endpoints, from “demonstrating a significant reduction in the need for systemic corticosteroids or surgery” to “improvements in smell and chronic rhinosinusitis symptoms.”
Tracking a pre-specified group of patients who also has asthma — a common predicament among chronic rhinosinusitis sufferers — researchers also note an improvement in lung function and asthma control.
“With these data, Dupixent has now been shown to address this inflammation across the complete airway, which manifests in the upper respiratory tract as polyps and congestion, and in the lower airway as asthma,” said Regeneron president and CSO George Yancopoulos, who led the development team credited for the IL-4/IL13 antibody.
Add that to eczema, where the drug landed its first big OK, and it makes three Type 2 or allergic inflammatory diseases where Dupixent has “demonstrated significant late-stage efficacy,” he said in a statement.
That context is key for Geoffrey Porges of Leerink, who maintains that despite the strength of the data and the clear potential benefit, “the greatest boost from nasal polyposis will be from incremental share gains in other co-morbid atopic/allergic conditions.” He explains:
Barriers to adoption in this indication will be the high cost and continuing burden of treatment ( ~$36,000/year and biweekly injections) and the different physician population (ENT surgeons) treating polyps, who may not be incentivized to treat with a biologic agent versus procedure. To the extent some of these patients are identified and in the care of allergists already, they may be more accessible for Dupixent, but surgeons are likely to be slower converters to injectable treatment.
“(W)e look forward to working with regulatory authorities around the world to make Dupixent an option for people living with this chronic condition,” added John Reed, global head of R&D at Sanofi.
Porges estimates regulatory filings in 2019 and FDA approval, if it is to come, in 2020.
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