A Phase 3 trial of ruxolitinib did not meet its primary endpoint of statistical significance in mortality due to any cause through day 29, in patients on mechanical ventilation with COVID-19 associated Acute Respiratory Distress Syndrome (ARDS).
The DEVENT study was a randomized, double-blind, placebo-controlled trial that enrolled a total of 211 patients. They were randomized to receive either ruxolitinib 5mg twice daily (BID) plus standard of care (SoC), ruxolitinib 15mg BID plus SoC or placebo plus SoC.
Despite not achieving the primary endpoint in the overall population, Incyte, the maker and sponsor of the study, said that statistical significant improvement in mortality was achieved in the US population (N=191; 91%). In the US, the 5mg treatment group had a 46.7% mortality rate vs 69.1% for placebo group (95% CI: 0.157-0.948, P =.0189), while the 15mg group had a 47.1% mortality rate vs 66.7% for the placebo group (95% CI: 0.188-0.974, P =.0215).
Additionally, a post-hoc analysis of the overall study population that pooled both the 5mg and 15mg ruxolitinib arms together vs placebo, showed a statistically significant improvement in mortality of 53.6% vs 70.7% (95% CI: 0.219-0.996, P =.0244).
The safety profile was generally consistent with treatment with ruxolitinib. The most common adverse events on the ruxolitinib arms, regardless of dose, compared to placebo were anemia (20.7% vs 22.2%), increased alanine aminotransferase (ALT, 14.6% vs 13.3%), increased aspartate transaminase (AST, 14.0% vs 8.9%) and hypertension (11.6% vs 11.1%), respectively.
Pending agreement with the Food and Drug Administration, Incyte said they plan to make ruxolitinib available to eligible patients in the US at no cost via an Expanded Access Program (EAP). This protocol will allow eligible patients with severe COVID-19 associated ARDS with disease severity requiring mechanical ventilation to receive ruxolitinib.
The Company indicated that there is ample commercial and clinical supply of ruxolitinib to meet the needs of US patients receiving ruxolitinib in its approved indications and those participating in clinical trials or the COVID-19 EAP.
“We hope the results of this study […] will contribute to the advances being made across the scientific community to alleviate the burden this pandemic has placed on patients, as well as the healthcare system. We look forward to discussing the results of the DEVENT study with regulatory authorities in the United States,” said Steven Stein, MD, Chief Medical Officer, Incyte.
Ruxolitinib is currently approved under the brand name Jakafi, to treat intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF; polycythemia vera in patients with an inadequate response to, or intolerant of, hydroxyurea; and for steroid-refractory acute graft-versus-host disease.
For more information visit incyte.com.
Incyte Announces Results from the Phase 3 DEVENT Study Evaluating Ruxolitinib (Jakafi®) as a Treatment for Patients with COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS) on Mechanical Ventilation. [press release]. Wilmington, DE: Incyte; March 19, 2021.