Sanofi/Regeneron asthma trial casts doubt on IL-33 class prospects

The good news for Sanofi and Regeneron is that their interleukin-33-targeting drug seems to work in asthma. The bad is that it doesn’t seem to be any better than their already-marketed drug Dupixent.

A phase 2 trial of the drug showed that REGN3500 significantly improved asthma control and lung function compared to placebo, providing proof-of-concept that targeting IL-33 is a viable strategy in resistant asthma.

When pitted against Sanofi and Regeneron’s IL-4 and IL-33 inhibitor Dupixent (dupilumab), REGN3500 didn’t fare so well, with the latter drug numerically superior for all outcome measures even if the trial wasn’t statistically powered to separate the two drugs.

Moreover, a combination arm of the study found that giving REGN3500 and Dupixent together performed no better than Dupixent alone, suggesting that the new candidate is at best a therapeutic alternative to the marketed therapy.

Sanofi and Regeneron aren’t giving up on the asthma indication and say they intend to advance REGN3500 into a late-stage trial programme. They can of course take comfort from the fact that Dupixent is already approved for asthma as they explore the potential of REGN3500 in other indications such as atopic dermatitis and chronic obstructive pulmonary disease (COPD).

The REGN3500 results weighed heavy on the share price of AnaptysBio however, another company with an IL-33 inhibitor in development for asthma. Its drug – called etokimab – is heading for a placebo-controlled phase 2b trial in asthma later this year.

The market for biologic drugs for severe asthma is becoming increasingly crowded, with IL-5 inhibitors such as GlaxoSmithKline’s Nucala (mepolizumab), Teva’s Cinqair (reslizumab) and AstraZeneca’s Fasenra (benralizumab) all approved for eosinophilic asthma along with anti-immunoglobulin E drug Xolair (omalizumab) from Novartis/Roche.

If the results indicate inhibiting IL-33 isn’t any better at tackling the inflammatory pathways in asthma than rivals, AnaptysBio will have even more riding on the outcome of a mid-stage ATLAS trial of etokimab versus Dupixent in atopic dermatitis due to read out later this year.

Dupixent has been approved for atopic dermatitis in 2017 and after a slow start has started to gather momentum, with sales rocketing to $374 million in the first three months of this year.

AnaptysBio will need to top Dupixent, or at the very least show equivalency along with some other advantage such as a cleaner safety profile or improved dosing frequency, if it is to come close to EvaluatePharma’s sales projections of $395 million in 2024.