Dupixent Data Could Scratch A Regulatory Itch
Executive Summary
New pivotal data on Regeneron and Sanofi’s antibody in chronic urticaria are underwhelming, though probably sufficient for approval. A green light may beckon in bullous pemphigoid, too.
Sanofi and Regeneron Pharmaceuticals, Inc. are to take their mega-blockbuster Dupixent back to regulators in chronic itching by the end of the year after hitting the primary endpoint in a third Phase III trial in the disease. This could lead to the US Food and Drug Administration reversing its earlier decision to reject the drug – but the data do not look hugely competitive with other agents in this space.
Key Takeaways
- A third Phase III trial of Sanofi and Regeneron’s IL-4/IL-13 inhibitor Dupixent in chronic spontaneous urticaria has succeeded, potentially allowing US approval of the antibody at the second time of asking.
- However, the data do not appear as strong as that reported in trials of competing products.
- Pivotal data in bullous pemphigoid suggest the antibody is the first medicine to show significant steroid-sparing effect in this debilitating condition.
The partners also scored a victory with the IL-4/IL-13 inhibitor in the smaller indication of bullous pemphigoid, potentially allowing Dupixent to become the first targeted medicine to treat the disease in the US and EU.
Dupixent (dupilumab) is a wildly successful drug in dermatitis and asthma, but does not seem to work quite so well in chronic spontaneous urticaria (CSU) judging by data from its pivotal LIBERTY CUPID clinical program. One of these trials, Study A, indicated that the drug significantly improving itch and hives in biologic-naive patients – but another, Study B, in biologic-refractory patients, failed. (Also see "Sanofi Hits Rare Setback For Dupixent In Urticaria" - Scrip, 18 Feb, 2022.) The FDA knocked the partners’ approval application back last October, saying more data were needed.
Study C, in 151 biologic-naive patients taking standard-of-care antihistamines, has now read out, and showed statistically significant drops in weekly itch severity score and weekly urticaria activity score, which measures itching and hives. 30% of Dupixent-treated patients reported no urticaria – a complete response – compared with 18% of those on placebo, a significant difference.
The actual placebo-controlled results, however, look lackluster when stacked against the other biologicals in this area, including Novartis AG and Genentech, Inc. ’s approved Xolair (omalizumab), particularly since the Study C data are after six months’ treatment; data from all the other trials in the below graph are at three months.
A later cut of the REMIX trials, both of which enrolled biologic-naive and -experienced patients, showed a more emphatic treatment effect for Novartis AG’s BTK inhibitor remibrutinib at six months, further highlighting Dupixent’s underwhelming performance. (Also see "Remibrutinib REMIXes The Itch Record" - Scrip, 28 Feb, 2024.)
Safety was standard for Dupixent, with the most common adverse event being injection site reactions, seen in 12% of Dupixent patients and 4% of placebo recipients.
Bullous Market
Separately, Regeneron and Sanofi reported data from another trial of Dupixent, this time in bullous pemphigoid, a disease in which blisters form on the skin. Mainly affecting older patients, it has a high mortality rate owing to the risk of infection.
In the pivotal ADEPT trial, 106 adults with moderate-to-severe bullous pemphigoid were given Dupixent 300mg every two weeks after an initial loading dose or placebo, along with standard-of-care oral corticosteroids (OCS). OCS use was tapered off after patients went two weeks with sustained control of disease activity, and only resumed if rescue treatment was required.
The study met the primary and “all key” secondary endpoints, Regeneron said, with five times more Dupixent patients achieving sustained disease remission compared with those on placebo. Sustained disease remission was defined as complete clinical remission with completion of OCS taper by week 16 without relapse and no rescue therapy use during the 36-week treatment period.
Safety looked acceptable, with no adverse events leading to death in the Dupixent group but two in the placebo group.
Few therapies are available for bullous pemphigoid, with standard of care being oral and topical corticosteroids and immunosuppressants; the former are not hugely effective and the latter can be dangerous, particularly in an older population. So the ADEPT data might well be enough for Dupixent to gain approval here, and a US submission will be made later this year.
Sanofi and Regeneron also revealed the failure of a small Phase III trial in uncontrolled and severe chronic pruritus of unknown origin. Dupixent did not achieve statistical significance on the primary endpoint of itch response, though “favorable numerical improvements” were seen. A second Phase III trial in this disorder is planned.
An FDA approval decision in COPD is also looming. But the sellside sees urticaria as a more important indication for Dupixent, forecasting sales of $2bn in 2030.