BioCryst Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has lifted its partial clinical hold on the BCX9930 program. The company will resume enrollment in global clinical trials under revised protocols at a reduced dose of 400 mg twice daily of BCX9930. This includes the REDEEM-1 and REDEEM-2 pivotal trials in patients with paroxysmal nocturnal hemoglobinuria (PNH) and the RENEW proof-of-concept trial in patients with C3 glomerulopathy (C3G), immunoglobulin A nephropathy (IgAN) and primary membranous nephropathy (PMN).

Clinical evidence and recent laboratory studies have informed the company's hypothesis that crystals form in the kidneys of some patients. The company believes that lowering the dose to 400 mg and ensuring adequate hydration will dilute the concentration of drug in the urine below the threshold where crystals can form. On April 8, 2022, BioCryst announced that the company had voluntarily paused enrollment in BCX9930 clinical trials while it investigated observed elevations in serum creatinine (SCr) seen in some patients at the 500 mg twice daily dose.

The FDA subsequently placed the program on a partial clinical hold. Patients already enrolled in the trials and demonstrating clinical benefit were able to continue on therapy. PNH patients naive to C5 inhibitor therapy who received 400 mg twice daily in the Phase 1 clinical program (n=7) experienced a mean change from baseline increase in hemoglobin of 4.3 g/dL and required no transfusions, and no patients experienced an elevation in their SCr during dose-ranging at the 400 mg twice daily dose.

All observed cases of SCr elevations occurred at 500 mg twice daily.