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FDA approval process needs streamlining
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It is a condition once considered relatively rare, but has now been diagnosed in upwards of 30 million Americans, with as many as 30 million more affected. It is a condition once thought to involve only the elderly or those with severe autoimmune disease (Sjögren’s), but is now recognized among a much wider demographic. It is a condition once considered more of a “nuisance,” but is now viewed as a chronically debilitating disease with huge quality of life implications.
The condition, of course, is dry eye, which remains one of the most prevalent and vexing conditions doctors face daily. Whether primary care, contact lens, glaucoma or refractive surgery, dry eye adds an element of complexity to our care.
While we have made significant strides in identifying and treating dry eye, we are constantly in search of more effective treatments. It is for just this reason I am finding the FDA’s recent decision not to approve Shire’s lifitegrast perplexing ... and a bit disappointing. I understand the FDA’s request for more data regarding clinical trial data endpoints. But this begs the question of what constitutes appropriate endpoint(s) for a dry eye trial. It also begs the even bigger question as to whether the FDA should continue evaluating safety and efficacy – or safety alone.
Let me preface my comments by saying I am not anti-FDA. Since President Theodore Roosevelt first enacted the Food & Drug Act in 1906 to protect the public against food and drug adulteration, the FDA has served us well. Certainly, the elixir sulfanilamide tragedy of 1937 and the FDA’s decision to deny thalidomide approval in 1962 underscore the agency’s value. Interestingly, in these early days the FDA’s primary interest was one of safety.
It was not until the Kefauver-Harris Amendment in 1962 that the FDA took a greater interest in efficacy – fascinating in and of itself, as the thalidomide issue was one of safety. Over the years, the FDA’s regulatory hurdles have grown, culminating in a process now mandating a preclinical phase, application for investigational new drug, as well as phase 1, 2 and 3 clinical trials. All of this results in a process which, from conception to approval, can range from 8 to 12 years, according to Heilman, and cost hundreds of millions of dollars. While the FDA has done a great job of expediting reviews, much work remains in streamlining the entire process. This, again, begs the question as to whether the FDA’s primary focus should be one of safety, thereby allowing the marketplace (prescribers and patients) to determine efficacy.
There are a few things we do know. There is a strong consensus that most dry eye involves tear film instability and evaporation, with inflammation as a key consideration. We know anti-inflammatory agents, including cyclosporine, corticosteroids, essential fatty acids (EPA and DHA), doxycycline, azithromycin and nonsteroidal anti-inflammatory drugs, have – to varying degrees – proven successful in managing dry eye. We know lifitegrast, an integrin antagonist, quells inflammation by reigning in rogue lymphocytes. From a safety perspective, we know lifitegrast’s dropout rate is on par with placebo cohorts. Finally, we know Shire Pharmaceuticals is working closely with the FDA to answer questions and submit additional OPUS-3 study data, all in the spirit of keeping lifitegrast’s approval process on track.
In this issue, I encourage you to read “It is not too early to prepare for the possible introduction of lifitegrast.” Dr. Darrell White provides a great perspective and sage advice for – what I hope to be – an exciting new treatment option in our battle with dry eye.
- Reference:
- Heilman RD. Quality Assur. 1995;4:75-79.
Disclosure: DePaolis reports no financial interest in Shire Pharmaceuticals.