Methods for treatment of refractory generalized myasthenia gravis
Inventors
Bedrosian, Camille • O'Brien, Fanny • Wang, Jing Jing
Assignees
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Publication Number
US-12459992-B2
Publication Date
2025-11-04
Expiration Date
Abstract
The disclosure provides methods of treating myasthenia gravis (MG) in a subject in need thereof by administering to the subject a substance that specifically binds complement component 5 (C5). In certain embodiments, the substance that specifically binds C5 is a binding protein, such as an anti-C5 antibody.
Core Innovation
The invention relates to a method of treating refractory generalized myasthenia gravis in a patient in need thereof by administering a therapeutically effective amount of an eculizumab variant. The patient is positive for auto-antibodies binding to nicotinic acetylcholine receptor (anti-AChR), and the treatment is administered for at least 26 weeks with an eculizumab variant comprising a heavy chain amino acid sequence according to SEQ ID NO: 14 and a light chain amino acid sequence according to SEQ ID NO: 11.
The method targets anti-complement component 5 (C5) activity, including eculizumab and C5-binding variants. The described mechanism rationale is based on blocking C5 cleavage to C5a and C5b and preventing Membrane Attack Complex (MAC) formation while preserving proximal complement function.
The treatment context emphasizes refractory generalized myasthenia gravis, including patients with marked generalized weakness and bulbar signs and symptoms, and refractoriness to immunosuppressive therapy (IST) and/or needing chronic plasma exchange or IVIg. The document describes clinical assessment at about 26 weeks and supports improvements using MG-ADL, QMG, MGC, MG-QOL15, and Neuro-QOL outcomes, with additional extension outcomes into week 52.
Claims Coverage
The partial content identifies one independent claim. The claim coverage centers on administering a specific eculizumab variant defined by SEQ ID amino acid sequences for at least 26 weeks to an anti-AChR-positive patient with refractory generalized myasthenia gravis.
Eculizumab variant defined by SEQ ID heavy and light chains for refractory anti-AChR+ gMG
Administering a therapeutically effective amount of an eculizumab variant comprising a heavy chain amino acid sequence according to SEQ ID NO: 14 and a light chain amino acid sequence according to SEQ ID NO: 11 to a patient with refractory generalized myasthenia gravis who is positive for auto-antibodies binding to nicotinic acetylcholine receptor (anti-AChR).
At least 26 weeks of treatment
Administering the eculizumab variant for at least 26 weeks.
Across the identified independent claim, the central inventive requirements are treating refractory generalized myasthenia gravis in an anti-AChR-positive patient, using an eculizumab variant specified by SEQ ID NO: 14 (heavy chain) and SEQ ID NO: 11 (light chain), and administering the variant for at least 26 weeks. Dependent refinements in the provided claim set further specify dosing, route, prior IST failure context, named variants, and quantifiable clinical outcome thresholds after 26 weeks.
Stated Advantages
Eculizumab-associated improvements in MG-ADL.
Significant secondary outcomes including QMG.
Sustained efficacy through 52 weeks in an open-label extension.
Safety consistency through the longer-term period is described.
Improvement in clinically meaningful outcomes measured on MG-ADL, QMG, MGC, MG-QOL15, and Neuro-QOL after at least 26 weeks, with specified quantitative reductions for multiple endpoints.
Documented efficacy supported by trial and extension outcomes showing improvements over 26 weeks and into week 52.
Documented Applications
Treatment of refractory generalized myasthenia gravis (gMG) in a patient positive for anti-AChR auto-antibodies, evaluated in a randomized double-blind placebo-controlled trial (ECU-MG-301) and an open-label extension (ECU-MG-302).
Clinical evaluation of therapeutic effects using MG-ADL and multiple additional outcome instruments including QMG, MGC, MG-QOL15, Neuro-QOL fatigue, and EQ-5D, including responder analysis and dual responder analysis concepts.
Treating refractory generalized myasthenia gravis (including anti-AChR-positive patients) in a patient in need thereof.
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