Methods for treating multiple osteochondroma (MO)
Inventors
Lemire, Isabelle • Harvey, Michael • GROGAN, Donna Roy • Desjardins, Clarissa
Assignees
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Publication Number
US-10980778-B2
Publication Date
2021-04-20
Expiration Date
Abstract
The invention features methods for inhibiting the formation, reducing the size, and slowing the growth of an osteochondroma in a subject with multiple osteochondroma (MO) by administering to the subject palovarotene (also known as R667), or a pharmaceutically acceptable salt thereof. The methods described herein can also ameliorate complications associated with osteochondroma formation and growth in a subject with MO.
Core Innovation
The invention relates to a method of treating a subject with multiple osteochondroma (MO), also referred to as multiple hereditary exostoses (MHE). The method comprises administering to the subject an effective amount of palovarotene ((E)-4-(2-{3-[(1H-pyrazole-1-yl)methyl]-5,5,8,8 tetramethyl-5,6,7,8 tetrahydronaphthalene-2-yl}vinyl)benzoic acid) or a pharmaceutically acceptable salt thereof.
The invention addresses the problem of MO by inhibiting osteochondroma formation and reducing osteochondroma size and/or average size. It also includes slowing osteochondroma growth, including growth adjacent to growth plates and/or perichondrium and/or epiphysis, and growth on long bones and/or flat bones.
The treatment further reduces cartilage hyperplasia and ameliorates MO-associated complications. It includes treatment of children/adolescents that are not fully grown and/or skeletal immaturity while maintaining long bone growth without damaging growth plates, and it associates the treatment with reduction of BMP level and/or BMP signaling in perichondrium, epiphysis, and overgrown cartilage.
Claims Coverage
The claims coverage includes one independent claim directed to treating MO with palovarotene (or a pharmaceutically acceptable salt) by administering an effective amount, with dependent claims specifying treatment endpoints, mechanistic and biological tissue targets, subject eligibility, and dosing constraints.
Administering palovarotene for MO treatment
Administering an effective amount of palovarotene ((E)-4-(2-{3-[(1H-pyrazole-1-yl)methyl]-5,5,8,8 tetramethyl-5,6,7,8 tetrahydronaphthalene-2-yl}vinyl)benzoic acid) or a pharmaceutically acceptable salt thereof to a subject with multiple osteochondroma (MO).
Dosing by body weight using daily palovarotene ranges
Administering palovarotene according to the subject’s body weight using specified daily dosage ranges and daily dosage values for different weight brackets.
Reducing osteochondromas without growth-plate damage and reducing BMP signaling
Reducing osteochondromas and related affected bones in the subject without damaging the subject’s growth plate or interfering with normal bone growth, and reducing BMP level and/or BMP signaling in the subject’s perichondrium, epiphysis, and overgrown cartilage.
Maintaining long bone growth during treatment
Maintaining long bone growth in the subject during treatment with palovarotene.
Treating eligible subjects based on developmental status and mutant exostosin genes
Treating a subject who is a not-fully-grown child/adolescent and/or who has a mutant exostosin gene.
Inhibiting osteochondroma formation in MO
Inhibiting osteochondroma formation in the subject using MO as defined in the document.
Across the claims, the core inventive coverage is the palovarotene-based treatment of MO by administering an effective amount, with dependent features directed to MO outcomes, BMP level and/or BMP signaling in perichondrium, epiphysis, and overgrown cartilage, maintenance of long bone growth without growth-plate damage, subject eligibility tied to developmental status and mutant exostosin genes, and dosing constraints tied to body weight.
Stated Advantages
Inhibiting osteochondroma formation.
Reducing osteochondroma size and/or average size.
Reducing osteochondromas and related affected bones, including reducing number of lesions/bones affected.
Slowing osteochondroma growth.
Reducing cartilage hyperplasia.
Ameliorating MO-associated complications.
Maintaining long bone growth without damaging growth plates.
Reducing BMP level and/or BMP signaling in perichondrium, epiphysis, and overgrown cartilage.
Documented Applications
Treating a subject with multiple osteochondroma (MO) / multiple hereditary exostoses (MHE) by inhibiting osteochondroma formation and slowing osteochondroma growth.
Treating MO in children/adolescents that are not fully grown and/or with mutant exostosin genes while maintaining long bone growth without growth-plate damage.
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