101-PGC-005 improved hospitalized patients with COVID-19 faster than systemic dexamethasone in topline phase 2/3 results

1. In a 309-patient randomized trial, 101-PGC-005 shortened time to clinical improvement versus systemic dexamethasone (hazard ratio [HR] [HR] 2.31; P<0.0001).

2. Treatment-emergent adverse events occurred in 54.8% versus 54.5%, with no Grade 3 or higher events, serious adverse events, deaths or discontinuations reported in either group.

Evidence Rating Level: 2 (Good)

2MM Brief: 101 Therapeutics reported phase 2/3 results for 101-PGC-005, an investigational CD206-targeted dexamethasone prodrug, at ACR Convergence 2026. The adaptive, randomized, open-label, active-controlled trial enrolled 309 hospitalized adults with moderate COVID-19 inflammatory disease at six sites in India. Participants received 101-PGC-005 20 mg intravenously once daily for three days or systemic dexamethasone 6 mg intravenously once daily for five to 10 days, each with standard of care. The primary outcome was time to at least 2-point improvement on the World Health Organization (WHO) ordinal scale. The company reported faster improvement with 101-PGC-005 than with dexamethasone, with a HR of 2.31 (95% confidence interval [CI] [CI], 1.83–2.93; P<0.0001) and median times of 3 versus 4 days. Secondary outcomes favored 101-PGC-005 for reverse-transcription polymerase chain reaction viral clearance, with an HR of 1.47 (95% CI, 1.17–1.84; P=0.0001) and median times of 3 versus 5 days, and for day 5 discharge, reported as 77.4% versus 29.0%. No patient in the 101-PGC-005 arm received physician-initiated systemic glucocorticoid despite protocol permission. Treatment-emergent adverse events occurred in 54.8% versus 54.5%; no Grade 3 or higher events, serious adverse events, deaths or discontinuations were reported in either group. In separate phase I pharmacokinetic studies, the company reported subclinical trace levels of free dexamethasone and preserved morning cortisol and adrenocorticotropic hormone (ACTH) after repeated supratherapeutic dosing. The findings are from company-reported meeting data and a publicly available preprint that has not been peer reviewed; the trial was open-label, and the rheumatologic uses proposed by the company have not been studied. These results support further evaluation of 101-PGC-005 in COVID-19, while efficacy and safety in rheumatic diseases remain unestablished.

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