North Fairfax News

Inova Fairfax Hospital issued the following announcement on Sept. 1

Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), today announced the publication of results from a Phase 2 clinical trial evaluating the safety of fostamatinib for the treatment of hospitalized patients with COVID-19, in Clinical Infectious Diseases, an official publication of the Infectious Disease Society of America. The study was sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), in collaboration with Inova Health System.

“As cases of COVID continue to surge across the world, improved therapies for patients hospitalized with COVID-19 are urgently needed,” said Richard Childs, M.D., Clinical Director of the NHLBI at the NIH. “We are encouraged to see that for COVID-19 patients requiring hospitalization, fostamatinib in combination with the standard of care was shown to be well tolerated in the study. Patients treated with fostamatinib not only had less severe adverse events, but were observed to have improved clinical outcomes compared to those receiving placebo and standard of care.”1

The results from the 59 patient Phase 2 trial demonstrated that the addition of fostamatinib to standard of care (SOC), which included the antiviral remdesivir and the steroid dexamethasone, was well tolerated and associated with clinically meaningful improvement in clinical outcomes in hospitalized COVID-19 patients who required supplemental oxygen. While the study was not powered to test clinical efficacy, numerous prespecified secondary endpoints consistently favored fostamatinib, including mortality, time to sustained recovery, change in ordinal scale assessment, number of days on oxygen, and number of days in the ICU, suggesting that fostamatinib may provide an additional therapeutic benefit compared to current SOC alone.

“It’s reassuring to see that fostamatinib demonstrated a consistently well-tolerated safety profile for hospitalized patients with COVID-19 in this trial,” said Jeffrey R. Strich, M.D., principal investigator of the study and a physician at the NIH Clinical Center. “Additional studies are needed to confirm the efficacy findings and show how fostamatinib may address the dysregulated immune response observed in COVID-19 patients.”

Results were published online in a manuscript titled “Fostamatinib for the treatment of hospitalized adults with COVD-19, A randomized trial” and can be accessed here.

Key findings within the fostamatinib Phase 2 trial include:

• The study met the primary endpoint showing fostamatinib did not increase the incidence of serious adverse events (SASs) compared with placebo.
• The overall incidence of SAEs by Day 29 was approximately 50% less in the fostamatinib group (10.5%) compared with the placebo group (22.0%) (p=0.2). The most frequent SAE reported by Day 29 was hypoxia, occurring in one patient receiving fostamatinib and three patients receiving placebo.
• At Day 29, in the overall population there were zero deaths in the fostamatinib group compared to three in the placebo group (p=0.07). In more severe patients (ordinal scale 6 or 7), the difference was 0/19 patients in the fostamatinib group compared to 3/17 patients in the placebo group (p=0.049).
• There were four intubated patients in the trial on mechanical ventilation (ordinal scale 7) upon enrollment with two patients randomized to each treatment group. Both patients in the fostamatinib group were extubated and discharged from the hospital, while both patients in the placebo group deceased.
• The median number of days in the ICU was reduced by four days, from seven days (IQR* 2-10) in the placebo group to three days (IQR 2-5) in the fostamatinib group (p=0.07).
• The median number of days on oxygen was 8 (IQR 5-10) in the fostamatinib group compared to 20 (IQR 14-27) in the placebo group (p=0.2). The difference was even greater in more severe patients with the fostamatinib group at 10 days compared to placebo at 28 days (p=0.027).
• At Day 15, 65.5% of patients were free of supplemental oxygen in the fostamatinib group compared to 39.9% in the placebo group (p=0.08). In more severe patients, the difference was 57.9% compared to 20% (p=0.016).
• Fostamatinib was superior to placebo in accelerating improvement in clinical status from baseline by Day 15 (mean change -3.6 + 0.3 vs. -2.6 + 0.4; p=0.035) using ordinal scale assessments.
• The median time to recovery was 8 days in both groups. The greatest benefits were observed in more severe patients where the median time to recovery was reduced from 13 days (IQR 11-19) in the placebo group to 10 days (IQR 6-13) in the fostamatinib group.
• Despite general SOC use of both steroids and remdesivir in all 59 patients, there was a consistently greater reduction in NETosis and other inflammatory biomarkers (CRP, Ferritin, D-Dimer, Fibrinogen) in the fostamatinib group compared to the placebo group.

*IQR = Interquartile Range, is the range of the first and third quartiles of the range as a measure of spread.

“We are privileged to have partnered with the NIH in this very well-orchestrated randomized controlled study demonstrating the safety of fostamatinib in patients with COVID-19,” said Steven D. Nathan, MD, Medical Director, Advanced Lung Disease & Lung Transplant Program, Inova Health System. “We are not only encouraged by the drug’s safety profile, but also are excited by the suggestion of improved outcomes in the active treatment arm. This potential beneficial effect is further supported by robust biomarker work performed at the NIH. This study lays a solid foundation for the phase 3 clinical trial which is needed to confirm these results and which is now underway.”

“With the need remaining so great, we are very pleased with the growing body of evidence that suggests fostamatinib may provide clinical benefit for those patients hospitalized with COVID-19,” said Raul Rodriguez, President and CEO of Rigel. “Our larger Phase 3 clinical trial in COVID-19, which we expect to complete later this year, will provide us with further understanding of the safety and efficacy of fostamatinib and its potential as a new therapy for these patients.”

Phase 2 Clinical Trial Design

The Phase 2 double-blind, placebo-controlled clinical trial sponsored by the NHLBI, part of the NIH, in collaboration with Inova Health System, enrolled fifty-nine hospitalized patients with COVID-19 who were a 5 to 7 on the 8-point ordinal scale (requiring supplemental oxygen via nasal cannula or non-invasive ventilation, requiring mechanical ventilation or extracorporeal membrane oxygenation). Patients were randomly assigned to one of two cohorts: fostamatinib plus SOC and matched placebo plus SOC (1:1). Treatment was administered orally twice daily for 14 days, with a follow-up period through day 60. The primary outcome was the cumulative incidence of SAEs by Day 29. Notably, all patients received dexamethasone (or other steroid) and remdesivir.

Original source can be found here.