Candidate: Jakafi® / Jakavi® (ruxolitinib)
Type: Janus kinase (JAK1/JAK2) inhibitor first approved by the FDA in 2011, with indications in polycythemia vera, myelofibrosis, and acute graft-versus-host disease. Marketed as Jakafi in the U.S. by Incyte, and as Jakavi outside the U.S. by Novartis.
2021 Status: Incyte on March 19 acknowledged that Jakafi missed the primary endpoint of the Phase III DEVENT trial (NCT04377620) by failing to show statistical significance in mortality due to any cause through day 29, adjusted for Acute Respiratory Distress Syndrome (ARDS), in Jakafi (5mg and 15mg) plus standard of care (SoC) versus SoC in the overall 211-participant population of patients on mechanical ventilation with COVID-19 associated ARDS. (55.2% vs. 74.3% in the 5mg arm and 51.8% vs. 69.6% in the 15mg arm).
Results indicated a trend toward improvement in mortality, especially in the U.S. study population of 191 participants. In the U.S. study population (N=191), accounting for 91% of the DEVENT study patients, (46.7% vs. 69.1% in the 5 mg treatment arm; 47.1% vs. 66.7% in the 15 mg arm versus placebo). Also, a post-hoc analysis of the overall study population pooling both the 5mg and 15mg Jakafi arms together versus placebo, showed a statistically significant improvement in mortality (53.6% vs. 70.7%). Incyte said it plans to make Jakafi available to eligible patients in the U.S. at no cost via an Expanded Access Program (EAP) pending agreement with the FDA.
2020 Status: Incyte said May 5 it is launching a second Phase III clinical trial (RUXCOVID-DEVENT; NCT04377620) in the U.S. to evaluate the efficacy and safety of Jakafi plus standard of care therapy, compared to standard of care alone, in COVID-19 patients on mechanical ventilation and who have acute respiratory distress syndrome (ARDS).
Additionally, Incyte has launched an emergency Expanded Access Program in the U.S. to allow eligible patients with COVID-19 associated cytokine storm to receive Jakafi (NCT04355793).
In April, Incyte launched the Phase III RUXCOVID trial (NCT04362137), designed to assess the efficacy and safety of Jakafi/Jakavi plus standard-of-care (SoC), compared to SoC therapy alone, in patients aged ≥12 years with COVID-19 associated cytokine storm. RUXCOVID will enroll approximately 400 patients globally, with Incyte sponsoring the trial in the U.S. and Novartis, outside the U.S.
The trial’s composite primary endpoint is the proportion of patients who die, develop respiratory failure (require mechanical ventilation) or require intensive care unit (ICU) care by Day 29. Secondary endpoints include 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.
In the U.S., Incyte added, it intends to begin an open-label emergency Expanded Access Program (EAP) that will allow eligible patients with severe COVID-19 associated cytokine storm to receive Jakafi while it is being studied for that indication. The company added that it is increasing manufacturing efforts to respond to anticipated supply needs related to its COVID-19 studies.
Outside the U.S., Novartis has established an international compassionate use program for eligible patients, and said it is working to manage the anticipated increase in COVID-19 related requests for Jakavi without interrupting access for patients using the drug for its authorized indications. Novartis cited other efforts to fight COVID-19, including its $20 million global fund to support communities impacted by the disease, and its commitment of 130 million doses of hydroxychloroquine to support pandemic response.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: