ibuzatrelvir (PF-07817883) / Pfizer - LARVOL DELTA

Efficacy of Ibuzatrelvir on Sustained Overall Symptom Alleviation: Post-hoc Analysis from a Phase 2b Randomized Clinical Trial (IDWeek 2026) - No abstract available

Clinical • P2b data • Retrospective data • Infectious Disease

Synergistic effect of combinational SHEN26 and PF07817883 in SARS-CoV-2 infection. (PubMed, Virol Sin) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Development of a scalable amidation-dehydration telescope process for the synthesis of Ibuzatrelvir | Poster Board #1553 (ACS-Fall 2026) - "Ibuzatrelvir is a second-generation orally administered inhibitor of the SARS-CoV-2 Mpro that has enhanced metabolic stability compared to nirmatrelvir. Process refinements in distillation, solvent exchange, and crystallization delivered a reproducible, sustainable route which was demonstrated at multi-kilogram scale. The optimized process afforded ibuzatrelvir in high yield, purity, and potency while markedly reducing process mass intensity (PMI) and cycle time, establishing an efficient and industrially viable approach for long-term manufacturing."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study of How Ibuzatrelvir is Taken up Into the Blood of Healthy Adults After Taking Different Tablets of Ibuzatrelvir (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

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

A Multipart Phase 1 Study to Assess Safety and Pharmacokinetics of Ibuzatrelvir in Healthy Participants and Dose Selection for a Dose-Ranging Study. (PubMed, Clin Transl Sci) - P1 | "Ibuzatrelvir was safe and well-tolerated, with no serious or severe adverse events reported and no participants discontinuing. In conclusion, pharmacokinetics and safety were established for single-agent oral ibuzatrelvir, supporting the design and dose selection for further phase 2 trials and the continued development of ibuzatrelvir (NCT05580003)."

Clinical • First-in-human • Journal • P1 data • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study of How Ibuzatrelvir is Taken up Into the Blood of Healthy Adults After Taking Different Tablets of Ibuzatrelvir (clinicaltrials.gov) - P1 | N=17 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Inhibitory effects and structural analysis of drug candidate PF-07817883 against coronaviral main proteases (Mpro) and SARS-CoV-2 Mpro mutants. (PubMed, J Struct Biol ) - "Recently, PF-07817883 (ibuzatrelvir) has been developed against SARS-CoV Mpro by optimizing PF-07321332 (nirmatrelvir), showing broad-spectrum inhibitory efficacy against coronaviral Mpros. It shows that both E166N and E166R mutants exhibiting a certain degree of resistance to PF-07817883, the E166N mutant shows a more substantial impact on enzyme activity. These data provide molecular insights into broad-spectrum inhibition against selected coronaviral Mpros by PF-07817883 and the similarities and differences of PF-07817883 when bound to various Mpros, which will push the development of novel antivirals with pan-Mpro inhibitory efficacy."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

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 | Trial completion date: May 2027 ➔ Feb 2028 | Trial primary completion date: Dec 2026 ➔ Sep 2027

Trial completion date • Trial primary completion date • Infectious Disease • Multiple Myeloma • Novel Coronavirus Disease

Cross-resistance patterns in SARS-CoV-2 against 3CL protease inhibitors. (PubMed, Nat Commun) - "Here, we report the pathways to resistance for atilotrelvir and simnotrelvir, two 3CL protease inhibitors used for COVID-19 treatment, and ibuzatrelvir, a compound in late-stage clinical development...Moreover, viral inhibition assays demonstrate that there is not only strong cross-resistance between the emerged viruses against these three molecules, but also against two additional widely used antivirals, nirmatrelvir and ensitrelvir, as well. Cellular assays highlight S144A, E166A, and E166V as mediating broad resistance, with E166V having the strongest effects. These results have important clinical implications, including the need to carefully consider cross-resistance properties in salvage therapy and combination treatment, as well as emphasizing the need for the further development of SARS-CoV-2 antivirals with differing modalities."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study of How Ibuzatrelvir is Taken up Into the Blood of Healthy Adults After Taking Different Tablets of Ibuzatrelvir (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Pfizer

New P1 trial • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

C5091029: A Study to Learn How the Study Medicine Called Ibuzatrelvir is Taken up into the Blood of Healthy Adults After Taking Different Tablets of the Study Medicine Called Ibuzatrelvir. (clinicaltrialsregister.eu) - P1 | N=18 | Recruiting | Sponsor: Pfizer Inc. | Not yet recruiting ➔ Recruiting

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

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

Trial initiation date • Infectious Disease • Multiple Myeloma • 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

Trial initiation date • Infectious Disease • Multiple Myeloma • Novel Coronavirus Disease • Respiratory Diseases

C5091029: A Study to Learn How the Study Medicine Called Ibuzatrelvir is Taken up into the Blood of Healthy Adults After Taking Different Tablets of the Study Medicine Called Ibuzatrelvir. (clinicaltrialsregister.eu) - P1 | N=18 | Not yet recruiting | Sponsor: Pfizer Inc.

New P1 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

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