On Aug. 13, 2021, Rigel Pharma announced that the U.S. Food and Drug Administration (FDA) had informed the Company that clinical data submitted in late-May from a 59-patient NIH/NHLBI-sponsored Phase 2 trial of fostamatinib to treat hospitalized patients suffering from COVID-19 are insufficient for an emergency use authorization (EUA) at this time. The Company was concurrently conducting a larger Phase 3 clinical trial evaluating fostamatinib in hospitalized patients with COVID-19.

The broader clinical development program for fostamatinib is comprised of three ongoing studies and a recently completed Phase 2 study. These studies are evaluating a wide range of hospitalized patients, including those not on oxygen therapy, who are experiencing mild to severe COVID-19-related complications:

Rigel-led Phase 3 Trial. This ongoing Phase 3 clinical trial will evaluate the safety and efficacy of fostamatinib in hospitalized COVID-19 patients without respiratory failure that have certain high-risk prognostic factors. This multi-center, double-blind, placebo-controlled study will enroll ~308 evaluable patients to either fostamatinib plus SOC or matched placebo plus SOC (1:1). The primary endpoint of this study is the proportion of patients who progress to severe/critical disease within 29 days. The study has enrolled ~176 patients as of August 12, 2021, and enrollment is expected to be complete by year-end.

ACTIV-4 Host Tissue Phase 3 Trial. The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) study, initiated and funded by the National Heart Lung and Blood Institute (NHLBI), part of the National Institutes of Health, is a multi-site, randomized, placebo-controlled trial of therapies, including fostamatinib, targeting the host response to COVID-19 in hospitalized patients. The Master Protocol is designed to be flexible in the number of study arms, the use of a single placebo group, and the stopping and adding of new therapies. Each active arm will include approximately 300 patients. Eligible participants will include patients hospitalized for COVID-19 with laboratory-confirmed SARS-CoV-2 infection on oxygen therapy. The primary outcome is oxygen-free days through day 28. Secondary outcomes include hospital mortality, use of mechanical ventilation, and WHO scale scores. The study enrolled its first patient on July 22, 2021.

Imperial College of London IST. The Imperial College London Investigator-Sponsored Trial (IST) is a two-stage, open-label, controlled clinical trial of patients randomized (1:1:1) to fostamatinib, ruxolitinib, or SOC. The primary objective will be to determine the efficacy of fostamatinib and the efficacy of ruxolitinib compared to SOC to reduce the proportion of hospitalized patients progressing from mild or moderate to severe COVID-19 pneumonia. Rigel is providing support for this trial along with Novartis. 

NIH/NHLBI-sponsored Phase 2 Trial. This randomized, double-blind, placebo-controlled study, which has been completed, evaluated the safety of fostamatinib plus SOC and matched placebo plus SOC (1:1) in hospitalized patients with COVID-19 requiring supplemental oxygen. The primary endpoint was the cumulative incidence of serious adverse events (SAEs) by Day 29. As previously announced, the study met its primary endpoint of safety and provided evidence of broad and consistent improvement in numerous secondary endpoints including mortality, time to sustained recovery, change in ordinal scale assessment, number of days on oxygen, and number of days in the ICU. Results from this study have been submitted for publication in a peer-reviewed medical journal.

Rigel Pharmaceuticals is a biotechnology company dedicated to discovering, developing and providing novel small molecule drugs that significantly improve the lives of patients with hematologic disorders, cancer and rare immune diseases. Rigel’s pioneering research focuses on signaling pathways that are critical to disease mechanisms. The company’s first FDA approved product is TAVALISSE^® (fostamatinib disodium hexahydrate) tablets, the only oral spleen tyrosine kinase (SYK) inhibitor for the treatment of adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment. The product is also commercially available in Europe (TAVLESSE) and Canada (TAVALISSE) for the treatment of chronic immune thrombocytopenia in adult patients.