Planned Phase III Trial of Ruxolitinib Plus Standard-of-Care for Patients with COVID-19

Planned Phase III Trial of Ruxolitinib Plus Standard-of-Care for Patients with COVID-19

April 7, 2020

Incyte announced that they are working with the FDA to initiate a phase III clinical trial to assess ruxolitinib (Jakafi) plus standard-of-care in patients with coronavirus disease 2019 (COVID-19) induced cytokine storm.

Incyte announced that they are working in partnership with the FDA to initiate a phase III clinical trial to evaluate the efficacy and safety of ruxolitinib (Jakafi) plus standard-of-care (SoC), compared to SoC therapy alone, in patients with coronavirus disease 2019 (COVID-19) induced cytokine storm.1

The global collaborative study, titled RUXCOVID, will be sponsored by Incyte in the US, and Novartis outside of the US. 

Moreover, Incyte is also expecting to initiate a separate open-label emergency Expanded Access Program (EAP) in the US. The protocol will allow patients who are eligible with severe COVID-19 associated cytokine storm to receive ruxolitinib while it is being investigated for this indication. 

“Our intent is to build on emerging evidence from independent studies to further establish the role ruxolitinib could play in balancing immune response to the infection and therefore potentially improving outcomes of patients with COVID-19 associated cytokine storm,” Steven Stein, MD, chief medical officer for Incyte, said in a press release.2 “We recognize the significant and urgent medical need of patients with severe COVID-19 infection, and we are working with the FDA in an effort to rapidly advance the RUXCOVID and EAP studies.” 

In a letter published in The Lancet, researchers suggested that accumulating evidence indicates that a subgroup of patients with severe COVID-19 may have a cytokine storm syndrome.2 Given this finding, it was recommended that identification and treatment of hyperinflammation use existing, approved therapies with proven safety profiles to address the urgent need to reduce the rising mortality.

“All patients with severe COVID-19 should be screened for hyperinflammation using laboratory trends (e.g., increasing ferritin, decreasing platelet counts, or erythrocyte sedimentation rate) and the HScore to identify the subgroup of patients for whom immunosuppression could improve mortality,” the authors wrote. “Therapeutic options include steroids, intravenous immunoglobulin, selective cytokine blockade (eg, anakinra or tocilizumab) and JAK inhibition.

Cytokine storm syndrome in patients with COVID-19 was described as resembling secondary hemophagocytic lymphohistiocytosis. Further, characteristics of this cytokine storm profile in patients with severe COVID-19 include increased IL-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumor necrosis factor-α. 

Additionally, the researchers also noted that JAK inhibition, similar to ruxolitinib, could potentially affect both inflammation and cellular viral entry in COVID-19.

Ruxolitinib is a first-in-class JAK1/JAK2 inhibitor that is currently approved by the FDA for the treatment of polycythemia vera in adults who have had an inadequate response to or are intolerant of hydroxyurea, in adults with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis, and for the treatment of steroid-refractory acute graft-versus-host disease in adult and pediatric patients 12 years and older.

The most common side-effects associated with ruxolitinib for certain types of myelofibrosis and polycythemia vera include low platelet count, low red blood cell count, bruising, dizziness, and headache. In patients with acute graft-versus-host disease, side-effects include low red blood cell counts, low platelet counts, low white blood cell counts, infections, and fluid retention. 

References:

1. Incyte Announces Plans to Initiate a Phase 3 Clinical Trial of Ruxolitinib (Jakafi) as a Treatment for Patients with COVID-19 Associated Cytokine Storm [news release]. Wilmington, Delaware. Published April 2, 2020. investor.incyte.com/news-releases/news-release-details/incyte-announces-plans-initiate-phase-3-clinical-trial. Accessed April 3, 2020.

2. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. doi:10.1016/S0140-6736(20)30628-0.