The laws governing ophthalmic drug and device approvals have changed little in recent years. But the FDA is making significant and far-reaching changes in its approvals process.
On the drug side, sponsors can expect a renewed emphasis on risks and benefits compared to existing products. And on the device side, new final and draft advices are changing the way sponsors and FDA reviewers approach approval decisions.
Two speakers from the FDA offered the latest insider perspectives on the current approval processes during “FDA: Getting to New Horizons” at the 2016 Glaucoma 360 meeting.
There is no secret to gaining marketing approval for a new glaucoma medication. All sponsors have to do is follow the FDA’s familiar rules. A product must be both safe and effective.
The problem is determining the balance of safety and efficacy that will sway FDA reviewers. For many medications, higher efficacy is associated with lower safety–and vice versa.
“The last product I saw that had no adverse events had no efficacy,” said Wiley Chambers, MD, supervisory medical officer, Division of Transplant and Ophthalmology Products. “In order to get labeled for a particular indication, you have to pick the indication you wish to be labeled for and conduct ‘adequate and well-controlled trials,’ which are defined in law. And you have to demonstrate the product has the efficacy you think it has.”
Demonstrating efficacy in glaucoma doesn’t have to be difficult, Dr. Chambers continued. The agency has decades of experience with active ingredients, including timolol, latanoprost, travoprost, and bimatoprost. Sponsors are not obliged to compare their product candidates to these agents, but it can be a wise move.
“These are all products that we have seen in multiple trials,” Dr. Chambers explained. “We know how they behave, we know the safety, we know the efficacy. If you do a comparison to one of those products, you can compare yourself to something we think is efficacious.
“And if you are more efficacious than one of those products, we think you can probably tolerate more adverse events. If you are less efficacious than that product, you should have less adverse events. We didn’t set out to create those comparators, but without them, it becomes difficult to set some kind of bar,” he added.
Shortcuts don’t work when it comes to clinical trials, he continued. The FDA still expects sponsors to conduct at least two phase III clinical trials to demonstrate safety and efficacy, as well as nonclinical studies to evaluate carcinogenicity and other properties that are difficult to study in clinical trials.