Compositions and methods for treating late-onset Pompe disease

Patent metadata

Field	Value
Publication number	US-12533396-B2
Application number	US-202118009234-A
Country	US
Kind code	B2
Filing date	Jun 11, 2021
Priority date	Jun 14, 2020
Publication date	Jan 27, 2026
Grant date	Jan 27, 2026

Abstract

The present application provides methods of treating late-onset Pompe disease (LOPD) using a pharmaceutical composition comprising an oligosaccharide-acid α-glucosidase (GAA) conjugate, such as avalglucosidase alfa.

First claim

What is claimed is:

1 . A method for treating a late-onset Pompe disease (LOPD) in a human individual in need thereof, comprising administering to the individual a pharmaceutical composition comprising an oligosaccharide-protein conjugate and a pharmaceutically acceptable carrier, wherein the oligosaccharide-protein conjugate is avalglucosidase alfa
wherein the pharmaceutical composition is administered at a dose of about 20 mg/kg, wherein the individual shows the first symptom of Pompe Disease at an age of at least about 18 years old, and wherein administration of the pharmaceutical composition to a plurality of human individuals for 49 weeks results in one or more of the following:
(a) an average increase of FVC % in an upright position of at least about 1.1%, at least about 2.3%, or at least about 4.6%;
(b) an average increase of 6-minute walk test (6MWT) distance of at least about 12.5 m, at least about 23 m, or at least about 50 m;
(c) an average increase in 6MWT percentage of predicted value (6MWT %) of at least about 2%, at least about 3.5%, or at least about 8%;
(d) an average increase in maximum inspiratory pressure percentage of predicted value (MIP %) in an upright position of at least about 4.5%, at least about 8.7%, or at least about 12.5%;
(e) an average increase in maximum expiratory pressure percentage (MEP %) in an upright position of at least about 5.2%, at least about 10.9%, at least about 14.3%, or at least about 16.5%;
(f) an average increase in hand-held dynamometry (HHD) score for lower extremities of at least about 170 Newtons (N), at least about 250 N, or at least about 350 N;
(g) an average increase in HHD score for upper extremities of at least about 95 N, at least about 190 N, or at least about 245 N;
(h) an average increase in quick motor function test (QMFT) total score of at least about 2.7, at least about 3.3, or at least about 5.2;
(i) an average change of Gait, Stair, Gower's Maneuver, and Chair (GSGC) score of at least about −0.9, at least about −0.35, or at least about 0.40;
(j) an average increase of Gross Motor Function Measure (GMFM-88) Dimension D score of at least about 2.2, at least about 3.3, or at least about 5.8;
(k) an average increase of GMFM-88 Dimension E score of at least about 0.7, at least about 4.5, or at least about 5.2;
(l) an average increase in health-related quality of life Short Form 12 Health Survey SF-12®) physical component score (PCS) of at least about 0.4, at least about 3.7, or at least about 4.3%;
(m) an average increase in SF-12® mental component score (MCS) of at least about 0.45, at least about 3.4, or at least about 5.3;
(n) an average decrease in urinary hexose tetrasaccharide (HEX4) level of at least about 30%, at least about 43%, or at least about 78%;
(o) an average decrease in creatine kinase level of at least about 13%, at least about 39%, or at least about 63%;
(p) an average decrease in alanine aminotransferase (ALT) level of at least about 19%, at least about 38%, or at least about 68%; and
(q) an average decrease in aspartate aminotransferase (AST) level of at least about 26%, at least about 33%, or at least about 66%.

2 . The method of claim 1 , wherein the individual is:
(i) at least about 45 years old; (ii) between about 18 years old and about 45 years old; or (iii) no more than about 18 years old.

3 . The method of claim 1 , wherein the individual is diagnosed with Pompe disease at an age of at least about 18 years old.

4 . The method of claim 1 , wherein the individual:
(i) has not previously received treatment with a recombinant GAA; or (ii) has previously received treatment with a recombinant GAA.

5 . The method of claim 4 , wherein the recombinant GAA is alglucosidase alfa.

6 . The method of claim 1 , wherein prior to the treatment, the individual has at least one of the following characteristics:
(i) the individual has a forced vital capacity percentage of predicted value (FVC %) in an upright position between about 30% and about 85%; and (ii) the individual is able to ambulate for at least about 40 meters without stopping and without an ambulation assistance device.

7 . The method of claim 1 , wherein the individual has at least one of the following characteristics:
(i) the individual does not have Pompe-specific cardiac hypertrophy; (ii) the individual has confirmed GAA enzyme deficiency from any tissue source and/or at least 2 confirmed GAA gene variants; (iii) the individual is administered with the pharmaceutical composition for at least about 49 weeks; (iv) the individual has stable Mercuri scores, 3-point Dixon fat fraction, and/or T2 water with or without B1 correction according to skeletal muscle magnetic resonance imaging (MRI) over the course of the treatment; (v) the individual has lower risk of infusion-associated reaction (IARs) after receiving the treatment compared to that after treatment with alglucosidase alfa; and (vi) the individual has decreasing level of antidrug antibody (ADA) against the oligosaccharide-protein conjugate over time.

8 . The method of claim 1 , wherein the pharmaceutical composition is administered to the individual at least one of once every two weeks and intravenously.

9 . The method of claim 1 , wherein the pharmaceutical composition is reconstituted from a lyophilized formulation comprising the oligosaccharide-protein conjugate.

10 . The method of claim 9 , wherein the pharmaceutically acceptable carrier comprises about 10-50 mM histidine, about 0.25-2% glycine, about 1-4% mannitol, and about 0.005-0.05% polysorbate 80.

11 . The method of claim 1 , wherein administration of the pharmaceutical composition to the plurality of human individuals for 49 weeks results in one or more of the following:
(a) an increase of FVC % in an upright position that is at least about 2.43% higher compared to the increase of FVC % in an upright position in a plurality of human individuals treated with alglucosidase alfa; (b) an increase in 6MWT distance that is at least about 30.01 meters longer compared to the increase in 6MWT distance in a plurality of human individuals treated with alglucosidase alfa; (c) an increase in 6MWT percentage of predicted value (6MWT %) that is at least about 4.71% longer compared to the percent increase of 6MWT % in a plurality of human individuals treated with alglucosidase alfa; (d) an increase in maximum inspiratory pressure percentage of predicted value (MIP %) in an upright position that is at least about 4.40% higher compared to the increase in MIP % in a plurality of human individuals treated with alglucosidase alfa; (e) an increase in maximum expiratory pressure percentage of predicted value (MEP %) in an upright position that is at least about 2.51% higher compared to the increase in MEP % in a plurality of human individuals treated with alglucosidase alfa; (f) an increase in hand-held dynamometry (HHD) score for lower extremities that is at least about 106.97 N higher compared to the increase in HHD score for lower extremities in a plurality of human individuals treated with alglucosidase alfa; (g) an increase in HHD score for upper extremities that is at least about 63.87 N higher compared to the increase in HHD score for upper extremities in a plurality of human individuals treated with alglucosidase alfa; (h) an increase in quick motor function test (QMFT) total score that is at least about 2.08 higher compared to the increase in QMFT total score in a plurality of human individuals treated with alglucosidase alfa; (i) an increase in health-related quality of life Short Form 12 Health Survey (SF-12®) physical component score (PCS) that is at least about 0.77 higher com

Assignees

• Genzyme Corp

Inventors

• Finn Patrick
• Hamed Alaa
• An Haack Kristina
• Wilson Catherine

Classifications

• C12Y302/0102

  Alpha-glucosidase (3.2.1.20) · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61K47/549 Primary

  Sugars, nucleosides, nucleotides or nucleic acids · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K38/47 Primary

  acting on glycosyl compounds (3.2), e.g. cellulases, lactases · CPC title