Adagio gets a second chance

 A month ago the future looked bleak for Adagio Therapeutics. Today the company has a chance at resurrection, with surprisingly positive data from the pivotal Stamp and Evade trials of its Covid antibody adintrevimab (ADG20) that had been unblinded early. Still, there are reasons to be cautious about adintrevimab’s chances in the current Covid climate. The studies, in the treatment and prophylaxis settings, appeared to show some evidence of efficacy against the Omicron variant – albeit in small exploratory analyses. But there are questions about how the antibody will perform against the BA.2 subvariant, which is fast becoming dominant. Notably, a recent Nature Medicine paper found that adintrevimab was inactive against BA.2 in vitro. It was BA.2 that did for Glaxosmithkline and Vir’s Xevudy, which had initially looked good against Omicron – last week, the FDA stopped its use in areas where the subvariant is prevalent. Adagio is “re-engineering” adintrevimab to improve efficacy against Omicron, but in the meantime will file for US emergency use authorisation for both treatment and prophylaxis in the second quarter. Shares surged 43% this morning, but the group is still only worth a tenth of what it once was.

Pivotal data with adintrevimab
Stamp (treatment of high-risk pts with mild-to-moderate Covid)
	Hospitalisation or death		Relative risk reduction
	Adintrevimab	Placebo
All patients	8/169	23/167	66%
Omicron patients	0/29	2/34	100%
Evade (prevention of Covid)
	Symptomatic Covid		Relative risk reduction
	Adintrevimab	Placebo
Post-exposure	3/173	12/175	75%
Pre-exposure	12/730	40/703	71%
Pre-exposure (Omicron) 56 days' follow-up*	N/A	N/A	59%
Pre-exposure (Omicron) 77 days' follow-up*	N/A	N/A	47%
*Prespecified exploratory analysis following emergence of Omicron in 402 participants. Source: company release.

 

The Covid antibody landscape
Product	Company/ies	US status	Activity against Omicron?
Ronapreve (casirivimab + imdevimab)	Regeneron	EUA Nov 2020 for treatment of mild/moderate Covid	No
Bamlanivimab + etesevimab	Lilly	EUA Feb 2021 for treatment of mild/moderate Covid	No
Xevudy	Glaxosmithkline/Vir	EUA May 2021 for treatment of mild/moderate Covid	Yes, but not BA.2 subvariant
Evusheld	Astrazeneca	EUA Dec 2021 for pre-exposure prophylaxis; outpatient filing due H1 2022	Yes, and BA.2 subvariant
Bebtelovimab	Lilly	EUA Feb 2022 for treatment of mild/moderate Covid	Yes, and BA.2 subvariant
Adintrevimab (ADG20)	Adagio	Positive data from ph3 Stamp (treatment) and Evade (prophylaxis) studies; EUA planned	Yes, but not BA.2 subvariant
Source: Company & FDA releases. https://www.evaluate.com/vantage/articles/news/trial-results-snippets/adagio-gets-second-chance