ibuzatrelvir (PF-07817883) / Pfizer - LARVOL DELTA

Ibuzatrelvir, a second-generation SARS-CoV-2 protease inhibitor (ESCMID Global 2026) - "Organised by Pfizer"

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

IPT09 - Ibuzatrelvir, a second-generation SARS-CoV-2 protease inhibitor (ESCMID Global 2026) - "Organised by Pfizer"

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Learn About a Study Medicine Called Ibuzatrelvir in Adult and Adolescent Patients With COVID-19 Who Are Not Hospitalized But Are at Risk For Severe Disease (clinicaltrials.gov) - P3 | N=2330 | Recruiting | Sponsor: Pfizer | Trial completion date: May 2027 ➔ Mar 2028 | Trial primary completion date: Dec 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Ibuzatrelvir potently reduced viral RNA levels despite a high rate of anti-S seropositivity: a post hoc analysis of serology of the phase 2b study. (PubMed, Sci Rep) - No abstract available

Journal • P2b data • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

C5091018: A Study to Learn About a Study Medicine Called Ibuzatrelvir in People With Coronavirus Disease 2019 (COVID-19) and a Severely Compromised Immune System (clinicaltrialsregister.eu) - P2/3 | N=94 | Recruiting | Sponsor: Pfizer Inc.

New P2/3 trial • Infectious Disease • Multiple Myeloma • Novel Coronavirus Disease • Respiratory Diseases

Characterization of the Cross-Resistance of SARS-CoV‑2 Main Protease Inhibitors, Ibuzatrelvir, Ensitrelvir, and Nirmatrelvir. (PubMed, ACS Pharmacol Transl Sci) - "Notably, the recombinant SARS-CoV-2 virus containing the Mpro L50F/E166A/L167F triple mutant is highly resistant to all three drugs in the antiviral plaque assay. These findings underscore the challenge posed by E166 mutations and highlight the need for resistance-resistant Mpro inhibitors as future therapeutics."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Analysis of Ibuzatrelvir's Activity Against SARS-CoV-2 Circulating Variants and In Vitro Resistance Mutations. (PubMed, Antiviral Res) - "Cross-resistance testing revealed that this double substitution retained susceptibility to remdesivir and also conferred resistance to nirmatrelvir. Ibuzatrelvir and nirmatrelvir remained active against viruses containing the ensitrelvir-specific resistance Mpro substitution M49L. The sustained efficacy of ibuzatrelvir against circulating variants, combined with the low prevalence of the E166V substitution, supports its continued evaluation in phase 3 studies."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Learn How the Study Medicine Called Ibuzatrelvir is Taken up Into the Blood in Healthy Chinese Adults (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion

Structural Analysis of Inhibitor Binding to the Feline Enteric Coronavirus (FECV) Main Protease. (PubMed, Viruses) - "This study presents crystal structures of four clinically relevant inhibitors-GC376, PF-00835231, nirmatrelvir, and ibuzatrelvir-bound to Mpro from the feline coronavirus strain FECV-UU23. We therefore propose to incorporate sterically constrained, functionally tailored heterocyclic moieties at the P3 site of known inhibitors which can optimally engage Q187, P188, and S189 residues of the S4 loop. The findings presented enhance understanding of inhibitor specificity and reinforce the promise of these inhibitor scaffolds for developing antivirals against feline coronavirus strains, with possible applications in broad-spectrum coronavirus therapy."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Learn How the Study Medicine Called Ibuzatrelvir is Taken up Into the Blood in Healthy Chinese Adults (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Pfizer

New P1 trial

Structural insights into the nirmatrelvir-resistant SARS-CoV-2 Mpro L50F/E166A/L167F triple mutant-inhibitor-complex reveal strategies for next generation coronaviral inhibitor design. (PubMed, RSC Med Chem) - "One such variant harbors a triple mutation in Mpro, L50F/E166A/L167F, that displays decreased potency for nirmatrelvir (IC50 ∼ 850-1600 nM) and ibuzatrelvir while viral replication remained similar to that of the wildtype (WT) virus. A co-crystal structure reveals tight inhibitor binding that is stabilized by a network of hydrogen bonds formed by the mutated residues A166 and F167. This study provides the groundwork for optimized Mpro inhibitors against potential emerging variants of SARS-CoV-2, as well as strategies for broad-spectrum inhibitor design against variants of Mpro."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Ibuzatrelvir Potently Reduced Viral RNA Levels Despite the High Rate of Anti-S Seropositivity: a Post Hoc Analysis of Serology in the Phase 2b Study in Adults Without Risk Factors for Severe COVID-19 (IDWeek 2025) - No abstract available

Clinical • P2b data • Retrospective data • Infectious Disease • Novel Coronavirus Disease

A Study to Learn About the Study Medicine Ibuzatrelvir in Adults With COVID-19 Who Are Severely Immunocompromised (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease

A Study to Learn About the Study Medicine Ibuzatrelvir in Adults With COVID-19 Who Are Severely Immunocompromised (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: Pfizer

New P3 trial • Infectious Disease • Novel Coronavirus Disease

Silaproline-bearing nirmatrelvir derivatives are potent inhibitors of the SARS-CoV-2 main protease highlighting the value of silicon-derivatives in structure-activity-relationship studies. (PubMed, Eur J Med Chem) - "One of the two prochiral silaproline methyl groups occupies space in the S2 pocket that is unoccupied in Mpro:nirmatrelvir complex structures, highlighting the value of sila-derivatives in structure-activity-relationship (SAR) studies. The combined results highlight the potential of silicon-containing molecules for inhibition of Mpro and, by implication, other nucleophilic cysteine enzymes."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Potent, Pan-Coronavirus Antiviral Activity of the Novel 3CLpro Inhibitor ALG-097558 (CROI 2025) - "Against Omicron subvariants, ALG-097558 is 3- to 9-fold more active than nirmatrelvir (the 3CLpro inhibitor in Paxlovid™). Other 3CLpro inhibitors in clinical development such as ensitrelvir and ibuzatrelvir demonstrated greatly reduced antiviral activity against α-CoVs...Conclusions ALG-097558 demonstrates potent, pan-coronaviral activity in preclinical experiments and is uniquely positioned as a treatment option for SARS-CoV-2 infection and potential future coronavirus pandemics. After having demonstrated a favorable clinical safety and PK profile in Phase I, including ritonavir-free dosing, ALG-097558 warrants further evaluation in patients with COVID-19."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Learn if Study Medicines Called Cyclosporine and Clarithromycin Affect How the Body Processes the Other Study Medicine Called PF-07328948 in Healthy Adults (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Pfizer

New P1 trial

A Study to Learn How Renal Impairment Affects the Pharmacokinetics of PF-07817883. (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Renal Disease

A Study to Learn If the Study Medicine Called Carbamazepine Changes How the Body Processes the Other Study Medicine Ibuzatrelvir in Healthy Adults (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion

A Study to Learn If the Study Medicine Called Carbamazepine Changes How the Body Processes the Other Study Medicine Ibuzatrelvir in Healthy Adults (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Learn About if the Study Medicine Called Ibuzatrelvir Changes How the Body Process the Other Medicine Dabigatran Etexilate in Healthy Adults (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Learn How Renal Impairment Affects the Pharmacokinetics of PF-07817883. (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=28 ➔ 8 | Trial completion date: Oct 2025 ➔ Feb 2025 | Trial primary completion date: Oct 2025 ➔ Feb 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Renal Disease

A Study to Learn About a Study Medicine Called Ibuzatrelvir in Adult and Adolescent Patients With COVID-19 Who Are Not Hospitalized But Are at Risk For Severe Disease (clinicaltrials.gov) - P3 | N=2330 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Learn About if the Study Medicine Called Ibuzatrelvir Changes How the Body Process the Other Medicine Dabigatran Etexilate in Healthy Adults (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Virologic Response and Safety of Ibuzatrelvir, a Novel SARS-CoV-2 Antiviral, in Adults With COVID-19. (PubMed, Clin Infect Dis) - P2 | "All 3 ibuzatrelvir doses were associated with robust antiviral activity and an acceptable safety profile, supporting continued clinical development."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases