Pfizer's Tofacitinib Meets Primary Endpoint in Phase 3 STOP-COVID Trial for Hospitalized COVID-19 Patients

Compiled and Translated | newborn

On June 16, Pfizer and the Academic Research Organization (ARO) of Hospital Israelita Albert Einstein (HIAE), a non-profit healthcare institution in São Paulo, Brazil, jointly announced that positive results from the STOP-COVID study have been published in the New England Journal of Medicine (NEJM).

STOP-COVID (NCT04469114) is a research collaboration between Pfizer, Inc. and HIAE-ARO, which served as the trial coordinating center. This is a multicenter, randomized, double-blind, placebo-controlled trial conducted at 15 sites in Brazil, enrolling adult patients hospitalized with COVID-19 pneumonia. In the study, patients were randomized in a 1:1 ratio to two groups: one group received tofacitinib 10 mg twice daily plus standard of care, and the other group received placebo twice daily plus standard of care, with treatment continuing for 14 days or until hospital discharge. The primary endpoint was the cumulative incidence of death and respiratory failure at 28 days. Overall, 89.3% of patients received corticosteroids during hospitalization, predominantly dexamethasone.

The trial demonstrated that the cumulative incidence of death or respiratory failure within 28 days was lower in the tofacitinib group (18.1%) than in the placebo group (29.0%) (risk ratio [RR] = 0.63; 95% CI: 0.41–0.97; p = 0.04). The all-cause mortality was 2.8% in the tofacitinib group versus 5.5% in the placebo group (hazard ratio [HR] = 0.49; 95% CI: 0.15–1.63).

Twenty patients (14.1%) in the tofacitinib group experienced serious adverse events, compared with 17 (12.0%) in the placebo group. Among the protocol-defined adverse events of special interest, one patient each in the tofacitinib group experienced deep vein thrombosis, acute myocardial infarction, ventricular tachycardia, and myocarditis; in the placebo group, one patient each experienced hemorrhagic stroke and cardiogenic shock. The incidence of serious infections was 3.5% in the tofacitinib group and 4.2% in the placebo group.

Otavio Berwanger, Director of ARO, stated: “We are encouraged by the primary results of this randomized trial of tofacitinib in hospitalized patients with COVID-19 pneumonia. This study was based on the hypothesis that JAK inhibition could attenuate systemic and alveolar inflammation in patients with COVID-19-associated pneumonia. The findings provide new information indicating that adding tofacitinib to the standard of care, which includes glucocorticoids, can further reduce the risk of death or respiratory failure in patients.”

Primary Outcomes of the STOP-COVID Trial: Cumulative 28-Day Mortality and Incidence of Respiratory Failure

In COVID-19 infection, increased disease severity may be associated with an inflammatory state. It is hypothesized that inhibition of JAK kinases may attenuate the inflammatory state, thereby improving prognosis.

It is worth noting that Eli Lilly/Incyte's oral JAK1/JAK2 inhibitor Olumiant (baricitinib) was granted Emergency Use Authorization (EUA) by the U.S. FDA in November 2020 for use in combination with Gilead's antiviral drug Veklury (remdesivir) to treat suspected or laboratory-confirmed COVID-19 in hospitalized adult and pediatric patients aged ≥2 years who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). The recommended dosage under the EUA is 4 mg of Olumiant administered orally once daily for 14 days or until hospital discharge.

In April this year, Eli Lilly/Incyte announced results from the Phase 3 COV-BARRIER (NCT04421027) study. The data showed that, in hospitalized patients with COVID-19, Olumiant plus standard of care reduced the risk of death at 28 days by 38% (p=0.0018) compared with placebo plus standard of care (including corticosteroids and remdesivir).

Tofacitinib is an oral JAK inhibitor developed by Pfizer that effectively inhibits the activity of JAK1 and JAK3, thereby blocking the signal transduction of multiple inflammatory cytokines. Existing studies have demonstrated that tofacitinib exhibits favorable therapeutic efficacy in various inflammation-related diseases, including rheumatoid arthritis, ulcerative colitis, and psoriasis.

Tofacitinib is the active pharmaceutical ingredient of Xeljanz, which was approved in the United States in 2012 as the first JAK inhibitor to be marketed. To date, Xeljanz has been approved for four indications for the treatment of: rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC), and active polyarticular-course juvenile idiopathic arthritis (pcJIA).

It should be noted that tofacitinib has not yet been approved or authorized for the treatment of patients with COVID-19. The drug should also not be used in patients with active serious infections.

Source: Data Published in New England Journal of Medicine Shows Pfizer’s Tofacitinib Meets Primary Endpoint in Brazilian Study in Patients Hospitalized with COVID-19 Pneumonia