Novartis announced the Phase III RUXCOVID study evaluating ruxolitinib on top of standard of care (SoC) therapy compared to SoC treatment alone in patients with COVID-19 did not meet its primary endpoint. Initial data show there was no statistically significant reduction in the proportion of patients on ruxolitinib plus SoC therapy who experienced severe complications, including death, respiratory failure requiring mechanical ventilation or admission to the intensive care unit (ICU) by Day 29, compared to SoC alone. The trial also did not show clinically relevant benefit among secondary and exploratory endpoints including mortality rate by Day 29, and time to recovery (no longer infected, or ambulatory with no or minimal limitations).
“While the RUXCOVID trial did not give us the results we hoped for, we will continue working with the medical community to analyze its findings to better understand COVID-19 and the role of JAK inhibition,” said John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis. “We would like to thank the front-line clinical teams and staff at each of the trial sites and the hundreds of patients who volunteered to participate and their loved ones. We are deeply grateful to them and will continue our dedicated scientific research into the ongoing global pandemic.”
In the trial, the proportion of patients who died, or required mechanical ventilation due to respiratory failure or ICU care by Day 29, the primary endpoint, was 12.0% for ruxolitinib plus SoC vs. 11.8% for placebo plus SoC (OR: 0.91 [95% CI: 0.48-1.73]; p=0.769)1. Ruxolitinib was generally well-tolerated, and a comprehensive analysis including safety data is ongoing. The results of RUXCOVID do not affect any ongoing trials for ruxolitinib in non-COVID-19 diseases.
RUXCOVID (NCT04362137) is a Phase III multicenter, randomized, double-blind, placebo-controlled, 29-day study to evaluate the efficacy and safety of ruxolitinib plus standard of care (SoC) therapy compared to placebo plus SoC therapy in patients aged ≥12 years hospitalized for COVID-19 and not intubated or receiving ICU care prior to randomization. The study has enrolled 432 patients globally.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox! Sign up now!
The composite primary endpoint is the proportion of patients who die, develop respiratory failure (require mechanical ventilation), or require admission to ICU by Day 29. Secondary endpoints include various efficacy assessments including evaluation of clinical status using a 9-point ordinal scale; in-hospital outcomes (mortality rate; proportion of patients requiring mechanical ventilation; duration of hospitalization, ICU stay, supplemental oxygen, invasive mechanical ventilation); change in the National Early Warning Score (NEWS2); change in SpO2/FiO2 ratio; proportion of patients with no oxygen therapy (oxygen saturation of ≥94% on room air); and safety. The exploratory endpoint of time to recovery (no longer infected, or ambulatory with no or minimal limitations) was also evaluated.
Eligible patients were randomized 2:1 to receive oral ruxolitinib 5mg twice daily (BID) or oral-matching placebo for a total of 14 days. Study treatment is given in combination with SoC therapy according to the investigator’s clinical judgement. After 14 days of therapy, should clinical signs or symptoms not improve or worsen, and the potential benefit outweighs the potential risks, patients may receive an additional 14 days of study therapy. In total, patients are followed on study for 29 days post-randomization.
RUXCOVID is sponsored by Novartis outside of the US and by Incyte in the US.
Ruxolitinib is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. It is approved under the trade name Jakavi® in Europe and other regions and countries for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF), also known as chronic idiopathic MF, post-polycythemia vera MF or post-essential thrombocythemia MF. Approved indications vary by country. The safety and efficacy profile of Jakavi has not yet been established outside of its approved indications.
Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the US. Ruxolitinib is marketed outside the US by Novartis as Jakavi®, and in the US by Incyte Corporation as Jakafi® for patients with PV who have had an inadequate response to or are intolerant of hydroxyurea, for patients with intermediate or high-risk MF, and steroid-refractory acute GvHD in adult and pediatric patients 12 years and older. Jakavi is a registered trademark of Novartis AG in countries outside the US. Jakafi is a registered trademark of Incyte Corporation.