EP-4739293-A2 - COMPOSITIONS AND METHODS FOR THE TREATMENT OF AUTOIMMUNE DISORDERS

Abstract

Described herein are compositions and methods for the treatment of an inflammatory or autoimmune disease or disorder associated with conditions in or around an eye of an individual in need thereof. Said compositions and methods comprises providing a pharmaceutically (e.g., ophthalmically acceptable) composition comprising a keratolytic agent to an ocular or periocular surface of the individual in need thereof.

Inventors

• RAFAELI, OMER
• ALSTER, YAIR
• BOSWORTH, CHARLES
• GLEESON, Marc

Assignees

• AZURA OPHTHALMICS LTD

Dates

Publication Date

20260513

Application Date

20240705

Claims (20)

1. 1. A method for treating an inflammatory or autoimmune disease or disorder associated with keratinization of an eyelid margin or posterior surface of an eyelid or an ocular surface of an individual, the method comprising providing to a periocular surface of the individual a pharmaceutical composition comprising a keratolytic agent and an ophthalmically or pharmaceutically acceptable vehicle or carrier.
2. 2. The method of claim 1, wherein the inflammatory or autoimmune disease or disorder affects mucous membrane(s) of the individual.
3. 3. The method of claim 1, wherein the inflammatory or autoimmune disease or disorder affects skin of the individual.
4. 4. The method of claim 1, wherein the inflammatory or autoimmune disease or disorder affects both the mucous membrane(s) and skin areas of the individual.
5. 5. The method according to claim 1 or 2, wherein the inflammatory or autoimmune disease or disorder is associated with ocular manifestations.
6. 6. The method of any one of the preceding claims, wherein the individual has Sjogren's Syndrome, Rheumatoid arthritis, Systemic lupus erythematosus (SLE), Behget's disease, Sarcoidosis, Graft-versus-host disease (GvHD), Stevens-Johnson syndrome (SJS), erythema multiforme, toxic epidermal necrolysis (TEN), psoriasis, ichthyosis, Lichen planus, atopic dermatitis, Ocular cicatricial pemphigoid (OCP), Vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), exposure keratopathy (EK), or post chemical bums (e.g., exposure to strong acids or alkalis that causes severe damage to the ocular surface).
7. 7. The method of any one of the preceding claims, wherein the inflammatory or autoimmune disease or disorder associated with keratinization of an eyelid margin or posterior surface of an eyelid comprises Sjogren's Syndrome, Rheumatoid arthritis, Systemic lupus erythematosus (SLE), Behget's disease, Sarcoidosis, Graft-versus-host disease (GvHD), Stevens-Johnson syndrome (SJS), erythema multiforme, toxic epidermal necrolysis (TEN), psoriasis, ichthyosis, Lichen planus, atopic dermatitis, Ocular cicatricial pemphigoid (OCP), Vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), exposure keratopathy (EK), or post chemical bums (e.g., exposure to strong acids or alkalis that causes severe damage to the ocular surface).
8. 8. The method of any one of the preceding claims, wherein the individual has SJS.
9. 9. A method for treating SJS in an individual, the method comprising providing to a periocular surface of the individual a pharmaceutical composition comprising a keratolytic agent and an ophthalmically or pharmaceutically acceptable vehicle or carrier.
10. 10. The method of any one of the preceding claims, wherein skin of the individual is affected by SJS.
11. 11. The method of any one of the preceding claims, wherein periocular surface of the individual is affected by SJS.
12. 12. The method of any one of the preceding claims, wherein mucous membrane of the individual is affected by SJS.
13. 13. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered to the periocular surface of the individual in a manner suitable to deliver the keratolytic agent to the affected skin and/or mucous membrane of the individual.
14. 14. The method of any one of the preceding claims, wherein SJS is characterized by (e.g., severe) burning, conjunctival ulcerations, membrane formation, and/or sloughing of surface epithelium, such as at the lid margin.
15. 15. The method of any one of the preceding claims, wherein SJS is characterized by chronic and/or long-term sequelae (e.g., of the skin, ocular, and/or periocular surface).
16. 16. The method of any one of the preceding claims, wherein SJS is characterized by dry eye, conjunctival scarring/deficiency, loss of limbal epithelial stem cells, and/or (e.g., heavy) keratinization, such as over the lid wiper zone and/or conjunctiva of the individual.
17. 17. The method of any one of the preceding claims, wherein SJS is characterized by lid margin keratinization (LMK).
18. 18. The method of any one of the preceding claims, wherein SJS is ocular SJS.
19. 19. The method of any one of the preceding claims, wherein the pharmaceutical composition is provided to or around the eye of the individual.
20. 20. The method of any one of the preceding claims, wherein the pharmaceutical composition is provided to the eye of the individual.

Description

COMPOSITIONS AND METHODS FOR THE TREATMENT OF AUTOIMMUNE DISORDERS CROSS REFERENCE [0001] The present application claims the benefit of U.S. Provisional Application No. 63/525,548, filed July 7, 2023, which is entirely incorporated herein by reference. BACKGROUND OF THE INVENTION [0002] Expression of keratinization of the Conjunctiva, posterior surface of the eyelid and meibomian glands are major contributing factors to ocular signs and symptoms of inflammatory and autoimmune eye disease and is often characterized by production of a keratinized material, which is uncommon in healthy eye. [0003] Keratolytic agents are highly irritable to the eye and cannot be applied without substantial precaution to avoid mucosal and corneal touch. Selenium sulfide (SeS?) is indicated for the treatment of dermatological condition such as seborrheic dermatitis, tinea versicolor and dandruff. It is typically used as shampoo, foam or lotion at commercially available concentrations of 1% and 2.5% and is applied for several minutes, then rinsed off. The use of SeS? can be associated with known side effects that are listed in the drug insert and which may include irritation, burning, and on rare occasion, loss and discoloration of hair. Contact of a significant amount of preparations containing high-concentration SeS? with mucous membranes of the eye may cause irritation (e.g., stinging) and prolonged contact (e.g., overnight application) of preparations containing SeS2 with the skin may cause local irritation. [0004] Adverse events reported following topical ocular use of SeS? containing products include: superficial punctate keratitis and conjunctivitis which resolved upon cessation of treatment. When SeS? is applied topically for the treatment of tinea versicolor, skin irritation may occur in the genital areas and/or folds of the skin. SeS? lotions can also cause rebound oiliness of the scalp. AHFS Drug Information 2010. SUMMARY OF THE INVENTION [0005] Patients with an inflammatory or autoimmune disease or disorder (e.g., Stevens- Johnson syndrome (SJS)) sometimes manifest conditions and/or disease in or around an eye (e.g., keratinization of an eyelid margin or posterior surface of an eyelid of an individual). For example, Stevens-Johnson syndrome (SJS)/Toxic epidermal necrolysis (TEN) is a dermatologic emergency, characterized by the presence of epidermal and mucosal bullous lesions. Severe damage to the skin and mucous membranes of certain inflammatory or autoimmune disease or disorder associated with keratinization of an eyelid margin or posterior surface of an eyelid or an ocular surface of an individual can make such inflammatory or autoimmune conditions have substantially negative life experience and/or even be life-threatening. Because the skin normally acts as a protective barrier, extensive skin damage can lead to a dangerous loss of fluids and allow infections to develop. In some instances, such conditions can affect the eyes as well, causing irritation and redness of the conjunctiva (e.g., the mucous membrane that line the eyelids and eye surface). Lid margin keratinization (LMK) is a chronic ocular sequela of SJS, which causes lid wiper epitheliopathy and progressive ocular surface damage. Prior to the methods described herein, there were no pharmacological agents useful for the treatment of disease or disorder associated with conditions in or around an eye. [0006] Provided in certain embodiments herein is a method for treating a disease or disorder associated with conditions in or around an eye. In some embodiments, a method comprises providing or administering a pharmaceutical (e.g., ophthalmically acceptable) composition to an ocular and/or periocular surface of an individual in need thereof (e.g., having a disease or disorder associated with conditions in or around an eye). In some embodiments, a pharmaceutical composition comprises one or more keratolytic agents (e.g., SeS?). In some embodiments, a disease or disorder comprises an inflammatory and/or autoimmune disease (e.g., SJS). In some embodiments, an inflammatory and/or autoimmune disease is associated with conditions in or around an eye (e.g., keratinization of an ocular and/or periocular surface, such as an eyelid, eyelid margin and/or posterior eyelid surface). In some embodiments, an individual in need thereof has a disease or disorder associated with conditions in or around an eye (e.g., keratinization of an eyelid margin or posterior surface of an eyelid). [0007] Provided in certain embodiment herein is a method for treating an inflammatory or autoimmune disease or disorder associated with keratinization of an eyelid margin or posterior surface of an eyelid of an individual in need thereof, the method comprising providing to a periocular surface of the individual a pharmaceutical composition comprising a keratolytic agent and an ophthalmically or pharmaceutically acceptable vehicle or carrier. [0008] Provided in certain embodiment herein is a met