ALLERGIC CONJUNCTIVITIS

Allergic conjunctivitis (AC) is a common ocular inflammatory manifestation of allergen exposure in sensitized individuals. The most consistent symptoms are redness and itching. Signs and symptoms of AC can decrease quality of life, interfere with productivity, and lead to a considerable economic burden. Seasonal allergic conjunctivitis comprises 90% of allergic conjunctivitis in the United States and the prevalence of AC is reportedly increasing [1]. Allergic affects up to 40% of the population in the United States [2] but only about 10% of individuals with allergic conjunctivitis seek medical attention, and the entity is often underdiagnosed and manage with over-the-counter medications and complementary non-pharmacological remedies [3]. 

The most common treatment options for AC consist of topical ophthalmic formulations intended to reduce inflammation and provide symptomatic relief [1], these medications require multiple daily doses, which can be inconvenient and may reduce treatment compliance.

Figure 2: Allergic conjunctivitis treatment [4]

Reproxalap (Aldeyra Therapeutics) is an immune-modulating reactive aldehyde species (RASP) inhibitor that works by covalently binding to free aldehydes and diminishing excessive RASP levels, which are generally elevated in ocular and systemic inflammatory disease. Reproxalap offers a new mechanism for reducing ocular inflammation in allergic conjunctivitis, dry eye disease, and anterior uveitis, which provide clear benefit on treatment of AC [5].

With uncheck growing disease burden and limited options beyond OTC/Rx antihistamines, reproxalap poised to potentially be the next novel entrant in the allergic conjunctivitis and dry eye market.

COMPETITION

The most common treatment options for AC consist of topical ophthalmic formulations intended to reduce inflammation and provide symptomatic relief.

One of the treatment options is targeted immunotherapy, in which the immune system is desensitized to triggering allergens through chronic exposure to low doses of specific allergens delivered subcutaneously or sublingually, is intended to desensitize individuals to triggering allergens and prevent the activation of inflammatory signaling pathways. Immunotherapy improves symptoms of SAC (e.g., itchiness, watery eyes, and red eyes) and may reduce AC medication use. [6,7]. Despite the effectiveness of immunotherapy, this treatment approach is not used by most patients. Further, many patients do not pursue desensitizing immunotherapy options recommended by their health care providers, and only a fraction of these patients complete therapy. [8]. Results of the Allergies, Immunotherapy, and Rhino-conjunctivitis study indicate that this may be because of treatment inconvenience, cost, or ineffectiveness [9]. The availability and efficacy of topical treatments for acute AC symptoms may also be a factor; many patients reported using prescription or nonprescription medications to manage their symptoms.

Another option is topical antihistamines, which are widely available without a prescription. Antihistamines competitively block histamine receptors (e.g., H₁ or H₄) on nerve endings and blood vessels of the mucosal surface, thereby reducing itchiness and conjunctival hyperemia. [10]. First-generation antihistamines were associated with a range of systemic adverse effects (e.g., sedation, dizziness, cognitive impairment, blurred vision) caused by anticholinergic actions and nonspecific binding to histamine H₂ receptors in addition to drying of the ocular surface. Topical antihistamines (e.g., levocabastine, emedastine difumarate) are useful for providing rapid relief of AC symptoms, but their duration of action is limited; most topical antihistamines require dosing four times daily. Moreover, Topical vasoconstrictors are highly effective at reducing ocular and conjunctival hyperemia through the stimulation of vascular α-adrenergic receptors. However, they are not recommended for long-term use because of reduced effectiveness over time and a potential rebound effect that can produce persistent red eye on discontinuation.

Furthermore, Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent the formation of pro-inflammatory mediators and disrupt the inflammatory cascade that contributes to itching in AC. However, NSAIDs require dosing four times daily, and their efficacy in managing AC is limited because they inhibit the production of only one type of inflammatory mediator (i.e., prostaglandins). Corticosteroids prevent the production of multiple classes of late-phase response mediators, including prostaglandins, leukotrienes, histamine, and some cytokines. The numerous points of intervention in the inflammatory cascade make glucocorticoids an effective pharmacologic therapy for AC, [11] but long-term topical use can lead to serious adverse effects, including increased intraocular pressure and corneal abnormalities.

There are no U.S. Food and Drug Administration (FDA)-approved therapies indicated to treat both dry eye disease and allergic conjunctivitis. Neither cyclosporine nor lifitegrast has been approved for use in patients with allergic conjunctivitis, and antihistamines are known to exacerbate ocular dryness. Thus, with the possible exception of topical corticosteroids, which cause glaucoma and other serious ocular toxicities in some patients, we believe that no currently available drug for dry eye disease or allergic conjunctivitis is likely to be effective for the treatment of patients who experience symptoms of both diseases.

In comparison, several independent studies showed that Reproxalap provides better outcomes and safety with fewer adverse drug reactions for the immune system.