1156. Sustained Alleviation and Resolution of Targeted COVID-19 Symptoms with Nirmatrelvir/Ritonavir versus Placebo

Abstract

Abstract Background Nirmatrelvir with ritonavir (nirmatrelvir/r) is an oral antiviral COVID-19 treatment. We report its efficacy to shorten time to sustained alleviation and resolution of COVID-19 signs/symptoms in nonhospitalized adults with COVID-19 at high risk of severe disease as of primary completion data cut (11 Dec 2021). Methods In this phase 2/3 double-blind study, eligible adults with confirmed SARS-CoV-2 and ≤ 5 days (d) of symptoms were randomized 1:1 to nirmatrelvir/r 300 mg/100 mg or placebo (PBO) every 12 hrs for 5 d. Pts logged presence and severity (on 3- or 4-point scales) of prespecified COVID-19 signs/symptoms daily Day 1 (pre-dose) through 28. Times to sustained alleviation and resolution of all targeted signs/symptoms were assessed, summarized with Kaplan-Meier curves, and compared by treatment by log-rank test. Individual signs/symptoms were compared with descriptive analyses. Results From Jul–Dec 2021, 2246 pts enrolled; 2085 pts (nirmatrelvir/r, n=1039; PBO, n=1046) met criteria for the mITT1 population (≤ 5 d of symptom onset, did not/not expected to receive an mAb). More pts achieved sustained alleviation or sustained resolution with nirmatrelvir/r. Shorter median times to sustained alleviation/resolution were observed with nirmatrelvir/r (13/16 d) vs PBO (15/19 d; Fig 1 & 2). Also, a shorter median time to sustained alleviation was seen in pts treated ≤ 3 d of symptoms with nirmatrelvir/r (12 d) vs PBO (15 d). The most common symptoms were cough, muscle/body aches, and headache in both groups. The median time to sustained alleviation of cough and headache was 2 d less with nirmatrelvir/r vs PBO. The median time to sustained resolution of muscle aches and shortness of breath was 3 d and 4 d less with nirmatrelvir/r. The proportion of pts with severe signs/symptoms in the nirmatrelvir/r vs PBO group was significantly higher at baseline, but significantly lower after treatment, showing nirmatrelvir/r significantly reduced symptom severity through Day 28 (Fig 3). Pts who were seronegative vs seropositive or had high vs low viral load at baseline achieved faster times to sustained alleviation with nirmatrelvir/r vs PBO. Conclusion Nirmatrelvir/r treatment reduced duration and severity of COVID-19 symptoms vs PBO in pts at high risk of progressing to severe disease. NCT04960202. Disclosures Jennifer Hammond, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Heidi Leister-Tebbe, BSN, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Annie Gardner, MPH, MSPT, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Paula Abreu, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Weihang Bao, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Wayne Wisemandle, MA, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Wajeeha Ansari, MPH, Pfizer Inc.: Stocks/Bonds Magdalena Alicja Harrington, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jesus Abraham Simón Campos, MD, AstraZeneca: Board Member|AstraZeneca: Speaker|Eli Lilly: Board Member|Pfizer: Board Member|Roche: Board Member|Roche: Speaker Kara W. Chew, M.D., M.S., Merck Sharp & Dohme: Grant/Research Support Rienk Pypstra, MD, MBA, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds James M Rusnak, MD, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds.