Rigel Pharmaceuticals, Inc. announced an upcoming oral presentation highlighting data from the FOCUS Phase 3 clinical trial of fostamatinib in hospitalized COVID-19 patients without respiratory failure who have certain high-risk prognostic factors at IDWeek 2023 being held October 11-15, 2023, in Boston, MA and provided an update on the ACTIV-4 Host Tissue trial of fostamatinib in hospitalized patients with COVID-19. This presentation reports severe COVID-19 is linked to hyperactivation of the host immune response involving signaling through multiple spleen tyrosine kinase (SYK) pathways. Fostamatinib is an orally administered potent and selective inhibitor of SYK that has been approved in the US, Canada, Japan, and Europe for the treatment of chronic immune thrombocytopenia (ITP).

The FOCUS Phase 3 clinical trial was a double-blind, randomized, placebo-controlled trial of fostamatinib in adults hospitalized for COVID-19 who required oxygen supplementation (NCT04629703). Patients were randomly assigned 1:1 to receive fostamatinib (150 mg BID administered orally) or placebo for 14 days. All patients additionally received standard of care at their hospital.

The primary endpoint was days on oxygen (days 1-29). A total of 280 patients underwent randomization (with 141 assigned to fostamatinib and 139 to placebo). The primary endpoint was met; those who received fostamatinib had lower mean days on oxygen than those who received placebo (4.8 vs.

7.6 days, p=0.0136). Fostamatinib showed significance or trend towards significance in all secondary endpoints of reducing mortality and morbidity compared to placebo. The mean change in the 8-point ordinal score from baseline to the average of Day 5 to 15 was significantly improved in patients who received fostamatinib vs.

placebo (p=0.0092). Furthermore, 6 patients were enrolled with baseline ordinal score of 6 (3 in each group). All patients in the fostamatinib group survived, and all in the placebo group died by Day 30.

A significantly higher proportion of patients who received fostamatinib were discharged from the hospital by Day 15 compared to placebo (p=0.0029). Significantly more patients were alive and oxygen-free by Day 29 and Day 60 with fostamatinib treatment in comparison to placebo (p=0.0213 and p=0.0271, respectively). Treatment-emergent adverse events were consistent with previous studies and were similar between the 2 groups.

The addition of fostamatinib to standard of care treatment resulted in significantly fewer days on oxygen, an improved 8-point ordinal scale score, and significantly more patients alive and oxygen-free by Day 60 compared to placebo in patients with COVID-19 requiring hospitalization and supplemental oxygen. On September 26, 2023, the Data and Safety Monitoring Board (DSMB) recommended that the fostamatinib study arm of the ACTIV-4 Host Tissue (NECTAR) platform cease enrollment. Based on their review of a conditional power analysis, the DSMB determined that there was an extremely low likelihood of fostamatinib providing benefits related to the primary outcome (Oxygen Free Days) or other secondary outcomes in patients hospitalized and on oxygen therapy for COVID-19.

No safety concerns were identified. The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, concurs with the DSMB's recommendations and has asked the trial investigators to cease enrollment, complete follow-up for participants already enrolled, and complete study closeout. The full study data will be analyzed and disseminated as previously planned.