Pfizer Begins Paxlovid Trial for Pediatric Population

This morning, Pfizer announced it has begun its EPIC-PEDS trial for its antiviral pill, Paxlovid (nirmatrelvir [PF-07321332] tablets and ritonavir tablets). The phase 2/3 trial will study children 6 to 17 years of age to evaluate the safety, pharmacokinetics, and efficacy of the therapy in non-hospitalized, symptomatic, children with a confirmed diagnosis of COVID-19 who are at risk of progression to severe disease.

“There is a significant unmet need for outpatient treatments that can be taken by children and adolescents to help prevent progression to severe illness, including hospitalization or death,” Mikael Dolsten, chief scientific officer and president, Worldwide Research, Development and Medical, Pfizer, said in a statement this morning.

The study is going to be an open-label, multi-center, single-arm study in approximately 140 pediatric participants. Initial enrollment features 2 cohorts. Cohort 1 will include children ages 6 to 17 weighing at least 88 lbs, and cohort 2 will have participants of the same age and weighing more than 44 lbs and less than 88 lbs.

In terms of the regimen, each of the cohorts will be doing the following:

• Participants enrolled in Cohort 1 will receive a Paxlovid pill(nirmatrelvir/ritonavir 300 mg/100 mg) orally twice daily for 5 days (10 doses total), the current authorized dosing for pediatric patients 12 years of age and older weighing at least 88 lbs.
• Participants enrolled in Cohort 2 will receive Paxlovid (nirmatrelvir/ritonavir 150 mg/100 mg) orally twice daily for five days (10 doses total).

Paxlovid is a SARS-CoV-2 main protease (Mpro) inhibitor therapy. It was developed to be administered orally so that it can be prescribed at the first sign of infection or, pending clinical success of the rest of the EPIC development program and subject to regulatory authorization, at first awareness of an exposure. Nirmatrelvir inhibits viral replication during proteolysis, which occurs before viral RNA replication. In preclinical studies, nirmatrelvir did not demonstrate evidence of mutagenic DNA interactions.

Back in December, the Food and Drug Administration (FDA) gave Pfizer an emergency use authorization for Paxlovid for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients—12 years of age and older weighing at least 88 lbs—with positive results of direct SARS CoV-2 viral testing, and who were at high-risk for progression to severe COVID-19, including hospitalization or death.

"Today's authorization introduces the first treatment for COVID-19 that is in the form of a pill that is taken orally—a major step forward in the fight against this global pandemic," Patrizia Cavazzoni, MD, director of the FDA's Center for Drug Evaluation and Research, said at that time. "This authorization provides a new tool to combat COVID-19 at a crucial time in the pandemic as new variants emerge and promises to make antiviral treatment more accessible to patients who are at high risk for progression to severe COVID-19."

This comes on the heels of the recent news of the Pfizer-BioNTech COVID-19 vaccine having lasting efficacy challenges in the pediatric population. Some in the public health community believe these can be remedied with an increase of antigen or a booster dose.