ADX-102 development status:
Two distinct formulations now in clinical testing.
ADX-102 ophthalmic solution for ocular inflammation.
Allergic conjunctivitis is a common inflammatory ocular disease that is thought to be mediated in part by aldehydes. Patients with allergic conjunctivitis have ocular itching, excessive tear production, swollen eyelids, and ocular redness. Some patients with allergic conjunctivitis do not respond adequately to anti-histamines (the current standard of care), and are then treated with topical corticosteroids, an anti-inflammatory medication that can lead to cataracts, glaucoma, ulcers on the front of the eye, and increased rates of ocular infections. Thus, there is a need for novel and safe medicines like ADX-102 that have demonstrated activity in mitigating the symptoms of allergic conjunctivitis.
Noninfectious anterior uveitis is a rare but severe and poorly treated ocular disease where aldehydes are associated with inflammation, fibrotic changes and lipid destruction that lead to surface irritation, pain, photophobia, redness, and in some cases, blindness. ADX-102 has demonstrated potential to reduce inflammation in noninfectious anterior uveitis.
Based on preclinical research and testing, we believe inflammatory diseases of the eye may also be partly mediated by aldehyde toxicity. Accordingly, Aldeyra has developed an eye drop formulation of ADX-102, which completed Phase I clinical testing for safety and tolerability in healthy volunteers.
In the first quarter of 2016, we announced positive data from our Phase IIa clinical trial of ADX-102 ophthalmic solution in patients with allergic conjunctivitis. Relative to baseline, the data indicated that ADX-102 clinically improved ocular itching and tearing scores after acute administration and after 14 days of dosing. These data represent the first time an aldehyde trap has demonstrated the potential to ameliorate human disease and suggest that aldehydes are important targets in inflammation.
In the second quarter of 2016, we announced positive data from our Phase II clinical trial of ADX-102 ophthalmic solution in patients with noninfectious anterior uveitis. ADX-102 reduced cell count in a manner comparable to standard-of-care topical corticosteroids, which are effective but toxic, leading to glaucoma and cataracts in many patients. Together with the positive data in allergic conjunctivitis, these results suggest that ADX-102 could be active in a broad array of inflammatory ocular diseases.
ADX-102 topical medication for the dermatological manifestations of SLS.
As ADX-102 has demonstrated fatty aldehyde trapping in human skin cells in preclinical studies, Aldeyra initiated a clinical trial of ADX-102 for the treatment of the dermatologic manifestations of Sjögren-Larsson Syndrome (SLS) in the form of a topical medication. Our goal is to improve the symptoms of the severe skin disorder called ichthyosis, which is believed to result from the aldehyde accumulation inherent in SLS. There is currently no FDA-approved therapy specifically for SLS.
In the third quarter of 2016, we announced positive data from our randomized, vehicle-controlled, double-masked clinical trial of topical dermatologic ADX-102 to treat the skin disease in patients with SLS. The skin of all ADX-102-treated patients improved, and the magnitude of improvement was statistically greater than that of vehicle-treated patients. The results of the clinical trial suggest that ADX-102 could be the first mechanistically directed therapy in SLS.
In order to help this process, Aldeyra has developed the Aldeyra Registry for SLS so that families with SLS can sign up. This will help connect families with SLS to Aldeyra to accelerate the development of a treatment.
The development of a systemic formulation of ADX-102
To treat the neurologic complications of SLS and SSADH Deficiency, we are developing a systemic formulation of ADX-102. Such a formulation dramatically broadens the potential therapeutic applications of ADX-102 and other aldehyde traps that we are developing.