Pharming Group N.V. announces the topline results from two randomized, open label, controlled, pilot clinical trials of patients hospitalized with COVID-19 treated with Ruconest (recombinant human C1 inhibitor) for the prevention of severe SARS-CoV-2 infection. The primary endpoint in both studies was disease severity on the 7-point WHO ordinal scale on Day 7.
In the US study, conducted under a Pharming IND, which had included 32 patients at the time of the interim analysis, patients treated with Ruconest plus standard of care had statistically significant lower WHO disease severity scores at Day 7 (mean 1.83, SD 0.65) as compared with those patients who received standard of care alone (mean 3.22, SD 1.86; p=0.0056). Data on secondary endpoints and biomarker evaluations were concordant with the primary endpoint findings.
In the investigator-led study, conducted in Switzerland, Brazil and Mexico and part of the National Research Program “COVID-19” (NRP 78) of the Swiss National Science Foundation (SNSF), which included 83 patients by the time of the interim analysis, no difference in the primary variable was observed between the treatment groups. However, there was a significant difference in disease severity at baseline, i.e., prior to treatment, between the groups. Specifically, patients in the Ruconest arm had statistically significant more severe disease than those patients in the standard of care arm (p=0.0324).
Although the two studies used a similar design and both enrolled patients who were being admitted to the hospital with severe pneumonia due to COVID-19 infection, different dosing regimens of Ruconest were used. In the Investigator-led study Ruconest was dosed in addition to the standard of care for three days, whereas in the US study it was four days. Also, there were differences in the patient populations enrolled and in the standard of care regimens administered.
The primary endpoint in both studies was disease severity on the 7-point WHO ordinal scale on Day 7. This endpoint has been suggested by WHO for clinical trials in patients with COVID-19 as it measures illness severity over time.
The trials were conducted following a compassionate use program, which saw encouraging results in patients who were administered Ruconest following hospitalization with COVID-19-related severe pneumonia. The results were first announced in April 2020 and subsequently published in Frontiers in Immunology in August 2020.
Anurag Relan MD, Pharming’s Chief Medical Officer comments: “These results indeed support our initial hypothesis on the need to control the hyperinflammatory process in patients with severe COVID-19 infection. It is unfortunate we cannot draw many conclusions from the investigator led study, due to the imbalance between the Ruconest-arm and the control group at the start of the trial. We, however, thank all of the principal investigators and their staff for conducting this important research in an extremely challenging environment. We will analyze the full results of these studies as we design future clinical trials with Ruconest for the treatment of COVID-19, as well as other serious conditions.”
Ruconest was well tolerated and no drug-related serious adverse events were observed in either study.
Both studies have now concluded, and the results will be published in peer-review medical journals.