AstraZeneca’s chronic obstructive pulmonary disease (COPD) candidate has hit the mark in a pair of phase 3 trials, delivering broad efficacy with a mechanism that yielded mixed data for Roche and Sanofi.
The Oberon and Titania trials assessed the effect of AstraZeneca’s anti-IL-33 antibody tozorakimab on the rate of moderate-to-severe COPD exacerbations. Guggenheim Securities analysts called expectations for the program “appropriately low” in a research note last month. Investors’ hopes took a hit after Sanofi and Regeneron’s itepekimab and Roche’s astegolimab, both of which block IL-33 signaling, failed trials.
Amid the skepticism, AstraZeneca has maintained that tozorakimab is a differentiated asset that could deliver peak sales of $3 billion to $5 billion. Friday, the drugmaker backed up its optimism with topline data from the phase 3 Oberon and Titania trials.
Tozorakimab cut the annualised rate of moderate-to-severe COPD exacerbations compared with placebo in the primary population, which was limited to former smokers. AstraZeneca also reported a win in the overall population, which included former and current smokers, and across all blood eosinophil counts and stages of lung function severity. Eosinophils are white blood cells that may add to inflammation.
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AstraZeneca said tozorakimab was generally well tolerated with a favorable safety profile. While all the drugmaker’s topline disclosures are positive, it has yet to share any safety or efficacy data. AstraZeneca plans to release the full data at an upcoming medical meeting.
The available evidence supports AstraZeneca’s assertions that tozorakimab has a differentiated profile. Unlike itepekimab and astegolimab, AstraZeneca’s candidate completely inhibits the ST2 and RAGE/EGFR signaling cascades. RAGE/EGFR affects mucus production, which drives exacerbations, and the epithelial remodeling that decreases lung function in COPD patients.
Trial designs could explain why AstraZeneca reported a clean sweep while its rivals posted a mix of wins and losses. TD Cowen analysts said in a note to investors in January that Roche reported greater benefit in people with more exacerbations in an astegolimab trial. AstraZeneca’s larger trials and enrollment closer to the end of COVID-19 lockdowns may have increased exacerbation rates, the analysts said.
Whatever the reasons, AstraZeneca has emerged as the first IL-33 player to show consistent efficacy. Sanofi and Regeneron reported one hit and one miss in their phase 3 itepekimab program. Roche posted a pivotal phase 2b hit and phase 3 miss for astegolimab.
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Ryan Crowe, senior vice president, investor relations and strategic analysis at Regeneron, said at a TD Cowen event this month that the company and Sanofi were exploring whether they can file for approval based on their successful phase 3 trial or will need to run another study. If the FDA demands a new trial, Crowe said Sanofi and Regeneron would need to discuss whether to invest to meet the request.
AstraZeneca is running two more phase 3 trials in COPD, Prospero and Miranda, and is also evaluating its anti-IL-33 antibody in severe viral lower respiratory tract disease and in asthma. The company expects to have Prospero and Miranda results in the first half of the year.
