It was announced today that Aldeyra Therapeutics had received a Complete Response Letter or CRL, from the FDA for its drug reproxalap for the treatment of patients with dry eye disease. This was a huge blow to the biotech, because it was the second time that this drug had been rejected. I believe there must have been some confusion with the FDA in terms of what is actually required to get its drug through the finish line so that it can eventually commercialize it.
Despite this setback, though, there is hope on the horizon, because as the FDA noted in the CRL, reproxalap had failed to demonstrate efficacy through several well-controlled studies. That’s the bad news, which of course means that the company won’t be able to get this drug to patients immediately. There is still hope, because it was specified that if Aldeyra conducts one more adequate and well-controlled study targeting these dry eye disease patients, then it should be okay.
Typically, if the company had to start a new study from scratch, it would be entirely bad news. However, it is one step ahead of the game, in that it already has an ongoing dry eye disease field trial and an ongoing chamber clinical study. It expects to announce data from both of these studies in Q2 of 2025. Should they pan out, then this will be the first step necessary to turn things around.
On the other hand, there is a second item that must be accomplished, which is that it expects an FDA Type A meeting within the next 30 days. If discussions with the U.S. agency go well, then all that will remain is the data to be released in the next several months. Such data is going to be crucial, in that if it is highly positive, then it should be able to resubmit its New Drug Application (NDA) of reproxalap to treat these dry eye disease patients by mid-2025.
Even better, if the NDA resubmission itself happens, then the review period is going to be a short 6 months. The hope is that patients get to have a drug like this to treat their disease. The reason why is because it is the only late-stage clinical topical treatment to be given in a chronic administration. A lot of these patients could benefit from a topical treatment like this.
The company has built itself to develop its RASP-modulator platform to reduce inflammation in inflammatory disorders. Thus, the company is also developing reproxalap for the treatment of patients with allergic conjunctivitis as well. In allergic conjunctivitis the tissue that lines the eyelids and covers the white of the eyes of a patient, the conjunctiva, becomes inflamed or swollen. This also helps generate the mucus layer part of the eye that helps to form tears. Furthermore, it is classified into two different types of disease, which are seasonal and perennial allergic conjunctivitis, respectively. Seasonal just deals with allergens that come about only during certain periods of the year.
On the other hand, perennial allergic conjunctivitis is year-round and is caused by indoor sources, which leads to symptoms for these patients. The thing is with dry eye disease, it is a lack of tear production that causes the dryness and subsequent symptoms. However, allergic conjunctivitis occurs with certain items that trigger a response that causes inflammation. Over-the-counter (OTC) medications can be used as first-line therapy to achieve relief, and this could be with something like artificial tears.
However, in some cases, the disease is so severe that antihistamines and artificial tears don’t help at all. This is where prescription-strength medications become necessary. This might be good for Aldeyra’s therapy to play a role because the goal is to treat these patients with topical administration to relieve itch symptoms. Instead of outright targeting the protein itself, this drug goes after the small protein-binding RASP molecules. The benefit of this is to be able to target these groups of proteins simultaneously, instead of one at a time.
Dry eye disease is a devastating disorder because it is the inability for the eyes to produce enough tears to keep them lubricated. In addition, even if tears are produced, they are insufficient in lubricating the eyes as intended. In turn, there are several symptoms that these patients experience, like burning/stinging of the eyes and blurry vision. Reproxalap works by inhibiting pro-inflammatory molecules known as reactive aldehyde species (RASP). Allergic conjunctivitis is an allergic reaction, and it causes inflammation in the clear tissue part covering the white of the eye.
The biotech should be in good shape so long as it is able to do well in the ongoing studies relating to the program of using reproxalap to treat patients with dry eye disease. If it can attain positive results, then it will definitely end up being in a good position to refile an NDA submission for the FDA to review again.