Another $2B COPD opportunity just hit a brick wall.

Yesterday, the Roche / Amgen IL-33 Astegolimab missed its primary endpoint in the Ph3 ARNASA study - the second failure of an IL-33 in a few months, after the Regeneron / Sanofi AERIFY-2 study of Itepekimab failed in May

Exhibit 1: Heatmap of headline COPD targets across key Pharma portfolios

Some quick reactions:

• The road ahead to potential approval will likely be long for both assets. A good comp is GSK's Nucala:

1. Ran all-comer parallel Ph3s where one turned out positive (METREX) and one did not (METREO) - FDA rejected the drug in 2018

2. GSK designed a new, more focused Ph3 using the learnings from the prior studies (MATINEE) which took several years to enroll and read out

3. Nucala was finally approved in COPD in May 2025 - nearly 7 years later, becoming just the 2nd biologic approved in this indication

Regeneron already flagged that a new Phase 3 would be required to support approval, as the studies still yet to read out (AERIFY-3 and AERIFY-4) are likely insufficient to convince regulators. This likely 5-7 year delay is why Regeneron stock dropped as much as 20% when the news broke.

• AstraZeneca's own IL-33 tozorakimab was the last to readout of the trio (est. early 2026), but now looks to have the pole position across its four Phase 3 studies. However, given the overlap in mechanism and consistent story we've seen so far, the results are likely, at best, a toss up.
• COPD is a highly heterogeneous disease we don't understand well, so while all-comers would be ideal for docs and patients, patient segmentation is increasingly the more sound strategy.

The challenge? It's tricky in practice since patients oscillate between smoking status and eosinophil levels can surge post-cessation. But, with smoking status, eosinophil count, and emerging inflammatory biomarkers making or breaking trials, niching down to more targeted profiles will be key to avoiding those brutal 5+ year development resets while getting more biologics successfully to market.

• Amidst this shuffle Dupixent emerges as a clear winner, with line-of-sight to tack on another ~$2B in COPD peak sales by 2030. Of course, the double edged sword is that this only makes the 2031/2032 LOE all the more painful for Regeneron, prompting more questions around how they plan to offset this revenue. M&A may be the only way out at this point.