Factor VIII polypeptide formulations
Inventors
Maloney, Kevin • Gage, Daniel • Abdul-Fattah, Ahmad
Assignees
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Publication Number
US-12403183-B2
Publication Date
2025-09-02
Expiration Date
Abstract
The present invention provides a formulation of a Factor VIII polypeptide, e.g., FVIII-Fc, and methods of using the same. The FVIII polypeptide can be a recombinant FVIII protein, a short-acting FVIII protein, or a long-acting FVIII protein. The pharmaceutical formulation comprising a FVIII polypeptide can be used for individual prophylaxis, weekly prophylaxis, episodic (on-demand) treatment, or perioperative management of hemophilia.
Core Innovation
The disclosed subject matter relates to pharmaceutical compositions comprising rFVIIIFc, a chimeric polypeptide fusion of a Factor VIII portion and an Fc region, formulated with sucrose, sodium chloride, L-histidine, calcium chloride, and polysorbate. The formulation is provided as a lyophilizate alongside sterile water for reconstitution in pharmaceutical kits containing separate containers. Specific formulation component concentration ranges are [procedural detail omitted for safety].
The disclosure reports clinical and pharmacokinetic findings for rFVIIIFc in hemophilia A treatment regimens, including individualized prophylaxis, weekly prophylaxis, and episodic treatment. Clinical results indicate that approximately 98% of bleeding episodes are controlled with one or two injections. The chimeric polypeptide exhibits an extended half-life compared with recombinant Factor VIII, with Factor VIII activity declining more slowly over time.
Claims Coverage
The three independent claims cover three inventive features directed to a pharmaceutical composition and two pharmaceutical kit configurations comprising a chimeric Factor VIII and Fc region polypeptide.
FVIII-Fc pharmaceutical composition
A pharmaceutical composition comprising a chimeric polypeptide with a FVIII portion and an Fc region, together with sucrose, sodium chloride, L-histidine, calcium chloride, and polysorbate 20 or polysorbate 80, wherein formulation concentration ranges are [procedural detail omitted for safety].
Lyophilizate and sterile water kit
A pharmaceutical kit comprising a first container with a lyophilizate containing the chimeric FVIII-Fc polypeptide and specified excipients, and a second container with sterile water for injections, wherein combining the contents produces a solution with formulation quantities that are [procedural detail omitted for safety].
Lyophilizate and sterilized water kit
A pharmaceutical kit comprising a first container with a lyophilizate containing the chimeric FVIII-Fc polypeptide, sucrose, sodium chloride, L-histidine, calcium chloride, and polysorbate 20, and a second container with sterilized water, producing a solution with formulation ranges that are [procedural detail omitted for safety].
The independent claims cover the excipient-containing FVIII-Fc composition and two kit configurations providing the lyophilizate and reconstitution water in separate containers for solution preparation.
Stated Advantages
A-LONG Phase 3 results report median annualized bleeding rates of 1.6 with individualized prophylaxis, 3.6 with weekly prophylaxis, and 33.6 with episodic treatment.
Approximately 98% of bleeds are controlled with one or two injections.
The reported rFVIIIFc half-life is about 19.0 hours, compared with 12.4 hours for recombinant FVIII (ADVATE®), and FVIII activity declines more slowly with rFVIIIFc than with rFVIII.
Documented Applications
Hemophilia A prophylaxis, including individualized prophylaxis and weekly prophylaxis regimens.
Bleed control and episodic treatment of bleeding episodes in hemophilia A.
Perioperative management in hemophilia A.
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