Glaxo’s latest asthma cull puts Astra in the spotlight

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Discontinuation of Glaxosmithkline’s anti-IL-33r antibody melrilmab, revealed in yesterday’s third-quarter presentation, casts more doubt on this approach to treating asthma. EvaluatePharma data suggest Astrazeneca is the only serious believer here, having just last month begun the phase II Frontier-3 trial with MEDI3506, an anti-IL-33 MAb. Lilly canned LY3375880 for lack of efficacy, Regeneron’s REGN3500 showed positive but unconvincing data, while Anaptysbio’s etokimab is on hold in asthma. Doubts have been growing about Glaxo’s respiratory franchise, which is now probably less important to future growth than oncology, where the Merck KGaA-derived bintrafusp alfa will generate possibly registrational biliary tract cancer data late next year. All eyes are on bintrafusp's head-to-head first-line NSCLC test against Keytruda. This trial’s co-primary endpoints have been upgraded from PFS and overall response to PFS and OS, and recruitment closed at 300 after passing a futility analysis, but the companies will not say when they expect results. Glaxo also revealed six-month delays, owing to the Covid-19 pandemic, to proof-of-concept data for GSK3377794 (anti-NY-ESO-1 TCR) in NSCLC and to an interim analysis of gepotidacin’s pivotal trial in urinary tract infection, now due in the second half of 2021 and first half of 2022 respectively.

Targeting IL-33/IL-33r in asthma
Project Company/ies Asthma trial Detail
MEDI3506 Astrazeneca Frontier-3 Trial started Sep 2020, ends Jan 2022
REGN3500 (SAR440340)  Sanofi/ Regeneron ACT15102 Beat placebo but failed to beat Dupixent; studies in COPD & atopic dermatitis completed
Etokimab Anaptysbio NCT03469934 On hold pending analysis of eczema failure; atopic dermatitis discontinued; rhinosinusitis trial ongoing
Melrilimab (GSK3772847) Glaxosmithkline/ J&J NCT03393806 Discontinued Oct 2020; licensed from J&J in 2016
LY3375880  Lilly Admire Terminated for lack of efficacy after interim analysis
Source: EvaluatePharma, company statements & clinicaltrials.gov.

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