Methods for treating heterotopic ossification

Inventors

Desjardins, Clarissa • GROGAN, Donna Roy • PACKMAN, Jeffrey Neal • Harnett, Mark

Assignees

Clementia Pharmaceuticals Inc

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Publication Number

US-11622959-B2

Patent

Publication Date

2023-04-11

Expiration Date


Abstract

The invention features dosing regimens and pharmaceutical formulations for oral administration of palovarotene. The dosing regimens can reduce heterotopic ossification, reduce the number of flare-ups, and/or reduce the severity of flare-ups in subjects suffering from fibrodysplasia ossificans progressiva.

Core Innovation

The invention relates to a method of reducing heterotopic ossification in a subject with fibrodysplasia ossificans progressiva by using palovarotene administered orally during a period when the subject is experiencing at least one flare-up symptom. The method applies a two-stage dosing approach in which palovarotene is administered at a daily amount of 20±1.0 mg for a period of 20 to 40 days, followed by a daily amount of 10±1.0 mg for a period of 14 to 112 days.

The dosing stages are tied to the flare-up period and are intended to reduce heterotopic ossification. The core approach is structured around dosing during flare-up symptoms and then maintaining dosing after the initial flare-up dosing period, with the transition from 20±1.0 mg/day to 10±1.0 mg/day presented as the overall dosing sequence.

The flare-up symptom context includes swelling, pain, erythema, warmth, stiffness, and decreased range of motion. The described embodiments also include palovarotene or a pharmaceutically acceptable salt thereof, and optional concomitant administration of agents such as an antihistamine and a skin emollient, including embodiments that specify systemic antihistamine administration.

Claims Coverage

The provided claim content explicitly covers one independent claim and dependent refinements. The inventive features center on a flare-up-timed two-stage oral palovarotene regimen for reducing heterotopic ossification, together with specified daily amounts and treatment durations, plus narrower duration ranges, conditional extension, selected flare-up symptoms, a weight threshold, and systemic antihistamine administration.

Two-stage flare-up oral palovarotene regimen to reduce heterotopic ossification

Administering palovarotene or a pharmaceutically acceptable salt thereof orally during a period when the subject is experiencing at least one flare-up symptom by administering 20±1.0 mg daily for 20 to 40 days and then 10±1.0 mg daily for 14 to 112 days.

Post-transition 10±1.0 mg daily duration refinement

Administering palovarotene 10±1.0 mg daily for 14 to 84 days.

Conditional extension of 10±1.0 mg stage based on continued flare-up symptoms

Administering palovarotene 10±1.0 mg daily for an additional 28 days after 84 days if the subject continues to experience at least one flare-up symptom.

Selected flare-up symptom categories

Selecting the flare-up symptom from swelling, pain, erythema, warmth, stiffness, and decreased range of motion.

Weight-threshold subject selection

Performing the method on a subject whose weight is greater than 60 kg.

Systemic antihistamine concomitant administration

Further specifying that the antihistamine is administered systemically.

The claim coverage centers on the palovarotene oral two-stage regimen during a flare-up period, with dependent refinements directed to narrower dosing durations, conditional extension tied to continued flare-up symptoms, defined flare-up symptom types, and additional subject and concomitant-administration constraints.

Stated Advantages

Reduces heterotopic ossification in a subject with fibrodysplasia ossificans progressiva.

Documented Applications

A method of reducing heterotopic ossification in a subject with fibrodysplasia ossificans progressiva during periods when the subject is experiencing at least one flare-up symptom.

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