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BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) today announced the withdrawal of its Investigational New Drug application (IND) for the antiviral nucleoside,
BCX5191, following a discussion with the U.S. Food and Drug Administration (FDA).
The FDA indicated concerns regarding the preclinical toxicity profile of BCX5191 at exposure levels that they believe are likely to be necessary to reduce viral load in patients infected with the hepatitis C virus (HCV). Patient safety remains BioCryst’s highest priority. BioCryst continues to believe that BCX5191 may be distinct from other Nucs in exhibiting antiviral potency in man at significantly lower doses than other Nucs in development based on preclinical results, and will therefore conduct additional preclinical studies to determine if low doses—i.e. doses that are not associated with toxicity in animals—exhibit meaningful viral load reductions in HCV infected animals. BioCryst will then determine whether to continue development of BCX5191, based on the results of these studies.
BioCryst agrees with the FDA’s cautious approach to the development of nucleoside and nucleotide inhibitors for HCV. Further, BioCryst believes that the recent occurrence of serious adverse events in HCV patients treated with BMS-986094, a nucleotide prodrug previously under clinical development by Bristol-Myers Squibb, has heightened safety concerns regarding this class of HCV inhibitors. FDA has previously placed clinical holds on other nucleotides under development.
Discovered by BioCryst, BCX5191 is a novel, oral, pan-genotypic adenine nucleoside analog targeting viral RNA polymerase for the potential treatment of patients with HCV. BCX5191 inhibits the viral RNA polymerase enzyme across genotypes 1-4 at sub-micromolar concentrations and it is active in replicon cell assays. In human liver cells, BCX5191 rapidly and efficiently converts into its active triphosphate form. In preclinical models, BCX5191 demonstrates high oral bioavailability and is actively transported into the liver, without requiring prodrug technology. PK modeling supports once-daily dosing in clinical studies and predicts that low doses of BCX5191 will show antiviral activity.