A phase 2 asthma trial of Sanofi and Regeneron’s REGN3500 has met its primary endpoint. But the IL-33 antibody performed numerically worse than Dupixent and showed little promise in combination with the approved drug.
Sanofi and Regeneron are putting REGN3500, also known as SAR440340, through a suite of asthma, atopic dermatitis and chronic obstructive pulmonary disease clinical trials to assess the effect of inhibiting the IL-33 protein in these patient populations. IL-33 is thought to be central to type 1 and type 2 inflammation, leading the partners to conclude REGN3500 may improve outcomes in a range of diseases.
The asthma trial enrolled 296 people with moderate-to-severe forms of the disease that were poorly controlled by inhaled corticosteroid and long-acting beta-agonist therapy, making them suitable candidates for biologic intervention.
REGN3500 outperformed placebo in terms of the proportion of patients who suffered loss of asthma control, resulting in the trial hitting its primary endpoint. And it triggered statistically significant gains in lung function as measured by FEV1.
The comparison to Dupixent, which won approval in asthma last year, was less flattering. While the trial was not powered to show differences between the active treatment arms, Sanofi and Regeneron noted patients who received Dupixent performed numerically better than their peers on REGN3500 across all endpoints. A Dupixent-REGN3500 combination did no better than Dupixent monotherapy.
Sanofi and Regeneron are yet to share efficacy data from the trial, but the top-line findings suggest REGN3500 may struggle to supersede Dupixent. The partners noted that REGN3500 worked best in patients with blood eosinophil levels above 300 cells/microliter. But Dupixent is also most effective in this subpopulation, raising doubts about the scope for REGN3500 to carve out a space in the indication.
"The results from this phase 2 proof-of-concept trial suggest that IL-33 monotherapy was less effective than Dupixent and that no benefit was gained from adding an IL-33 to Dupixent. If this is shown to be the case in adequately powered studies then the role of the IL-33 class in the treatment of asthma may be limited," Jefferies analysts wrote in a note to investors.
The heterogeneity of asthma means Sanofi thinks there is value in trying different approaches in the disease. But, while Regeneron committed to “working with Sanofi to advance REGN3500 through our asthma clinical trial program,” the French company gave equivocal support for the program.
“We have ongoing studies for SAR440340 in atopic dermatitis and chronic obstructive pulmonary disease. We will evaluate the results of these studies as well as the findings in asthma to determine the best path forward for this therapy,” Steve Pascoe, head of immuno-inflammation development at Sanofi, said in a statement.
The decision about the next steps for SAR440340 will take place against a backdrop of R&D changes at Sanofi, which is seeking to lessen its reliance on externally sourced programs.