Ibuzatrelvir, Pfizer drug for COVID-19 treatment, both as monotherapy and in combination with VEKLURY

Pfizer posted a Ph3 interventional, randomized, double-blind, superiority study evaluating ibuzatrelvir (oral, Mpro inhibitor) for COVID-19 treatment in non-hospitalized and hospitalized (not on supplemental oxygen) severely immunocompromised adults; both as monotherapy and in combination with VEKLURY. 

Ibuzatrelvir Ph3 IC Trial (Not Yet Recruiting):

• PCD / SCD: Dec 6, 2026 / May 6, 2027
• Enrollment: 300
• Trial Design:   
  • Arm 1: Ibuzatrelvir only
  • Arm 2: Ibuzatrelvir + IV Remdesivir combo
  • Arm 3: IV Remdesivir only
• Primary Endpoint: 
  • The difference in the proportion of participants with the composite endpoint of a) COVID-19-related ED visits with administration of supplemental oxygen, COVID-19 antiviral, or IV treatment; COVID-19-related hospitalization; or all-cause mortality, and b) Evidence of recurrent or persistent SARS-CoV-2 infection [Time frame: 38 days]
• Secondary Endpoints: Time to sustained symptom alleviation, viral load, safety
• Trial Sites: US and Japan
• Inclusion criteria includes severely immunocompromised participants who:
  • Solid organ or islet cell transplant recipient who is receiving immunosuppressive therapy
  • Active hematologic malignancy (eg, chronic lymphocytic lymphoma, non-Hodgkin lymphoma, multiple myeloma, acute leukemia)
  • Receipt of CAR-T-cell therapy or HCT either within 2 years of transplantation or who are receiving immunosuppressive therapy
  • Currently receiving B-cell depleting therapies (eg, rituximab)
• Exclusion criteria notes participants who:
  • have a current need for supplemental oxygen for COVID-19 treatment
  • are receiving dialysis or has severe renal impairment
  • have active liver disease
  • received any other COVID-19 antiviral for current infection

Assessment:

• Pfizer is also evaluating ibuzatrelvir in another global and larger Ph3 trial in non-hospitalized, high risk adult and adolescent patients for COVID-19 treatment who are unable or unwilling to take PAXLOVID. Based on both ibuzatrelvir Ph3 trial PCDs in December 2026, timeline assumptions project Pfizer could file and receive ibuzatrelvir NDA approval by YE 2027.
   
• Pfizer may be positioning ibuzatrelvir as a “catch-all” treatment option for any other high-risk patients who are ineligible for PAXLOVID and for severely immunocompromised patients. As past ibuzatrelvir Ph2 data showed no DDI risks nor dysguesia as seen with PAXLOVID, positive data from these Ph3 trials may likely pose a significant competitive threat; particularly if Pfizer is able to demonstrate ibuzatrelvir monotherapy is superior to VEKLURY mono or combo therapy in hospitalized patients.