IL-1 blockade for the topical treatment of ocular surface inflammatory disorders and the discovery of EBI-005, a novel IL-1 receptor inhibitor

Abstract

There remains a substantial unmet medical need in the treatment of ocular surface inflammatory disorders, such as moderate to severe dry eye disease (DED) and allergic conjunctivitis (AC). Topical ocular IL-1 inhibition has the potential to treat the signs and symptoms of DED and treat other ocular surface inflammatory disorders such as AC. The signs and symptoms of DED are driven by different biological processes but IL-1 is a major mediator of all of these biological processes. This biological validation of IL-1 blockade in ocular surface inflammatory disorders was the basis for the engineering of EBI-005, a potent protein-based IL-1 inhibitor designed for the convenient and effective topical treatment of ocular surface inflammatory diseases such as DED and AC.

Keywords::

• allergic conjunctivitis
• dry eye
• hyperalgesia
• IL-1
• IL-1R1 inhibitor
• inflammation
• ocular
• pain

Financial & competing interests disclosure

The author would like to acknowledge editorial assistance from G Dabiri. This article was based on EBI-005 studies NCT01748578 and NCT01745887. ES Furfine is an Employee and Officer of Eleven Biotherapeutics. The author was supported by funding from Eleven BIotherapeutics. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Dry eye disease (DED) and allergic conjunctivitis (AC) are two ocular surface inflammatory disorders.

• Management of moderate-to-severe DED is a significant unmet medical need (26 million patients in the USA, EU and Japan).

• Severe forms of AC are also of unmet medical need; they are a significant subset of the 15–40% of US population that suffer from all forms of AC.

• Restasis^® (cyclosporine) and corticosteroids are currently the standard of care for DED, but are not ideal treatment options due to lack of efficacy or risk of sight-threatening adverse events.

• AC is commonly treated with topical antihistamines and mast cell stabilizers, which do not provide adequate treatment of the signs and symptoms in severe patients.

• Ideal treatment for DED would be to reduce both the signs and symptoms of the disease.

• IL-1 may mediate both DED and AC.

• Topical IL-1 blockade may attenuate inflammatory ocular surface disorders (DED and AC) and reduce neuropathic pain (symptom of DED).

• A novel IL-1R1 inhibitor, EBI-005, has been engineered with the following characteristics: high potency for blocking the IL-1 receptor and thus IL-1α and IL-1β signaling; clinically well tolerated and comfortable as eye drops; and without ocular toxicities.

Notes