What works, what doesn’t and what’s next for COVID-19: Data Byte
A COVID-19 report card and look ahead to the next late-stage readouts
The rise of viral variants underscores the continued need to find new treatments for COVID-19, but so far, most therapeutic candidates have performed far worse in late-stage trials than vaccines.
All the vaccine candidates that have made it through Phase III testing have proven effective, particularly at preventing severe disease. Most therapeutic candidates, by contrast, have failed to benefit patients, and some that have met their endpoints offer modest benefit.
An analysis of Phase III readouts in BioCentury’s COVID-19 Clinical Trials Dashboard finds 11 out of 16 therapies tested in hospitalized patients did not meet their primary endpoint. The analysis included the U.K.’s RECOVERY trial, a large Phase II/III platform study.
Hydroxychloroquine takes the prize for failing in the most treatment settings, from pre-exposure prophylaxis to patients hospitalized with severe disease.
Antiviral mAb cocktails from Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and Eli Lilly and Co. (NYSE:LLY), the latter of which is partnered with AbCellera Biologics Inc. (NASDAQ:ABCL) and Shanghai Junshi Biosciences Co. Ltd. (HKEX:1877; Shanghai:688180), have been the standout performers among therapeutics, offering the first treatment options for outpatients. But the promise of antiviral mAbs to reduce the burden on hospitals by preventing progression to severe disease has been stymied by the difficulty of administering IV therapies to outpatients, highlighting the need for oral and subcutaneous treatments in the setting.
The next couple of months could bring data from late-stage trials of over two dozen therapies, including six oral or subcutaneous therapies in the outpatient setting and an IV mAb from Vir Biotechnology Inc. (NASDAQ:VIR).
In hospitalized patients, the majority of these candidates target the host immune system, aiming to avoid the runaway inflammation that drives severe disease.
C5 – Complement 5
DAMPs – Danger-Associated Molecular Patterns
DPP-4 (CD26) - Dipeptidyl peptidase-4
IL-1 – Interleukin-1
IL-2 – Interleukin-2
IL-6 – Interleukin-6
IL-17A – Interleukin-17A
JAK-1/2 – Janus kinase-1/2
PPARɑ – Peroxisome proliferation activated receptor alpha
PPARɣ – Peroxisome proliferation activated receptor gamma
SIGLEC10 – Sialic acid binding Ig like lectin 10
TNFɑ – Tumor necrosis factor alpha
SGLT2 – Sodium-glucose cotransporter 2
VPAC2 – Vasoactive intestinal peptide receptor 2