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Clinical Trials

106: First-in-Human Safety, Pharmacokinetics & Pharmacodynamics of the Oral Factor D Inhibitor BCX10013

Monday, September 9, 2024
5:00 PM – 7:00 PM ET

    Presenting Author(s)

  • LV

    Laurent Vernillet, PharmD, PhD, FCCP

    Vice President, Clinical Pharmacology
    BioCryst Pharmaceuticals, Inc.
    Durham, Connecticut, United States

    • 1st/Primary Author(s)

  • MD

    Matthew Davidson, PharmD

    Principal Clinical Pharmacologist
    BioCryst Pharmaceuticals, Inc.
    Durham, North Carolina, United States

    • Co-Author(s)

  • TC

    Tiffany Carpenter, BS

    Sr. Clinical Trial Manager
    Innoviva Specialty Therapeutics, Inc., North Carolina, United States

  • XC

    Xilin Chen, PhD

    Vice President, Research Biology
    BioCryst Pharmaceuticals, Inc.
    Birmingham, Alabama, United States

  • LM

    Lori Mixson, PhD

    Director, Biostatistics
    BioCryst Pharmaceuticals, Inc., North Carolina, United States

  • AP

    Anna Papinska, PhD

    Associate Director, Clinical Pharmacology
    Deciphera Pharmaceuticals, Colorado, United States

  • CP

    Cynthia Parker, BS

    Associate Director, Research Biology
    BioCryst Pharmaceuticals, Inc.
    Birmingham, Alabama, United States

  • LV

    Laurent Vernillet, PharmD, PhD, FCCP

    Vice President, Clinical Pharmacology
    BioCryst Pharmaceuticals, Inc.
    Durham, Connecticut, United States

  • DW

    Dennis Walling, MD, MMCI, FIDSA

    Vice President, Clinical Development, and Head of Clinical Research
    Seres Therapeutics, North Carolina, United States

Statement of Purpose, Innovation or Hypothesis: Factor D, the rate-limiting enzyme of the complement alternative pathway (AP), is an attractive drug target for complement-mediated diseases such as immunoglobulin A nephropathy, paroxysmal nocturnal hemoglobinuria, and C3 glomerulopathy. This abstract describes results from the first-in-human study for BCX10013, a potent and selective, orally bioavailable Factor D inhibitor. This was a randomized, double-blind, placebo-controlled evaluation of the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of oral BCX10013 in healthy participants.

Description of Methods & Materials: Safety and tolerability were evaluated via clinical and laboratory monitoring. Plasma concentrations of BCX10013 were measured using a validated assay; PD effects were assessed using the AP-specific Wieslab assay, which measures terminal complement C5b-9 formation following an ex vivo AP stimulus.

Data & Results:

Sixty-seven male and female participants (planned n = 6 BCX10013 and n = 2 placebo per cohort) were enrolled into 9 single ascending dose cohorts with doses ranging from 1 to 200 mg. Forty-seven male and female participants (planned n = 10 BCX10013 and n = 2 placebo per cohort) were enrolled into 4 multiple ascending dose cohorts with doses ranging from 20 to 160 mg once daily (QD) for 7 or 14 days.

BCX10013 was safe and generally well tolerated across all single and multiple dose levels. Following single doses, 24/67 (35.8%) subjects reported a treatment-emergent adverse event (TEAE). Following multiple doses, 28/47 (59.6%) participants reported a TEAE. One TEAE in the single-dose arm and 4 TEAEs in the multiple-dose arm were of moderate severity, all of which were considered unlikely related or not related to study treatment; all other TEAEs were mild. There was no obvious dose relationship with TEAEs. No serious adverse events, severe TEAEs, or clinically relevant laboratory abnormalities were reported.

Absorption of BCX10013 was rapid following oral dosing. Exposure was approximately dose proportional across the evaluated dose ranges. Accumulation was mild (approximately 30-40% in median area under the concentration vs. time curve) following multiple doses of BCX10013. The median terminal half-life following multiple doses was approximately 14-16 hours.

AP suppression as measured by the Wieslab assay was rapid, occurring ≤ 1 hour after the first dose. Extent and duration of suppression was dose related. All participants had ≥ 99% AP Wieslab suppression at 24 hours post dose following the highest single dose (200 mg) and 24 hours post last dose of the highest multiple-dose regimen (160 mg QD; Day 14).

Interpretation, Conclusion or Significance: Based on the safety, PK, and PD results of this first-in-human study, further evaluation of the therapeutic potential of BCX10013 in complement-mediated diseases is warranted.

Disclosures: All authors are employees/former employees of BioCryst Pharmaceuticals Inc. and may hold stock in the same. Study was funded by BioCryst Pharmaceuticals Inc.

Citations/References:

Additional Information/Authors: n/a