Ocular Therapeutix Revamps to Address FDA’s Dextenza Concerns

When Ocular Therapeutix resubmitted its new drug application for Dextenza late in June, it represented a milestone in the company’s effort to essentially reshape itself from a device to a pharma firm. And this time, Ocular thinks it has come up with the formula to gain FDA approval.

This latest new drug application (NDA) resubmission comes following the Food and Drug Administration’s complete response letter (CRL) one year ago. That CRL indicated concerns related to the manufacturing and quality, not safety or efficacy of the product itself. This is the second resubmission of the NDA, which was initially submitted in September 2015, then resubmitted in January 2017 after receipt of a CRL in July 2016.

Dextenza is a corticosteroid intracanalicular insert placed through the punctum, into the canaliculus, and it is designed to deliver dexamethasone to the ocular surface for up to 30 days without preservatives, for treatment of ocular pain following ophthalmic surgery. Following treatment, Dextenza is intended to resorb and exit the nasolacrimal system without the need for removal.

What’s Different This Time?

So why should we think this resubmission will succeed? The answer, as Scott Corning, senior vice president, commercial, explains, is that major changes were made in the ranks of the top executives. Previously, many of the company executives had a background in the device industry, and the FDA inspection of Ocular’s facilities was performed by agency pharmaceutical reviewers, because Dextenza is a pharmaceutical product. This inspection is what led to the concerns noted in the CRL. “They came in speaking pharma, and we were speaking device,” Corning says.

Founder and then-CEO Amarpreet Sawhney, PhD, saw the need for a different mind-set for the company, so he stepped down as CEO and named his own replacement, Antony Mattessich, who previously ran Novartis’ US respiratory, dermatology, and pediatrics group, and before that worked at Bristol-Myers Squibb. Following that change, six more of the top 10 executives were replaced with people from pharma. The key changes made – for the process of successfully meeting the requirements for this NDA – were the appointments of Kevin Hanley as senior vice president, technical operations, and Daniel Bollag, PhD, as senior vice president, regulatory affairs, pharmacovigilance and quality.

The company believes the changes in personnel and mind-set have led to progress in both manufacturing and quality oversight, the two areas the CRL identified as concerns. Now, Ocular Therapeutix executives believe the FDA will perform another inspection of the facilities before deciding on approval, and they have reason to believe the inspectors will be satisfied with the changes made. The changes made were not in the process itself; that will remain the same. The changes were in the way processes are measured, documented, and recorded, and specifically address the 483 observations the company previously received. More broadly, they instill continuous improvement in terms of quality systems and good manufacturing practice compliance.

Dextenza is intended to be an alternative to eye drops for post-surgical treatment in ophthalmology, as doctors look for ways to address the problem of noncompliance with drops. The drug is delivered encased in the company’s hydrogel delivery system. The gel, made of non-toxic polyethylene glycol, elutes medication at a tapering low-dose rate, eliminating the peaks and valleys associated with typical dosing.

The Pipeline

Corning notes that the overall change of philosophy within Ocular Therapeutix has led to changes in the company’s approach to products in its pipeline. Previously, the desire was to keep all pipeline products within the firm, and take them from start-up through clinical development to commercialization. Ocular Therapeutix will still develop some assets, including Dextenza, that way, but will look to collaborate with partners on other pipeline assets, which is more typical of the pharma world.

Ocular has two glaucoma products in development: an intracanalicular insert in Phase III trials; and an intracameral implant presently enrolling its first clinical study. In addition, the company is developing intravitreal implants for treatment of wet age-related macular degeneration, diabetic macular edema, and retina vein occlusion; all therapies will be encapsulated into the hydrogel delivery platform, which is programmable to elute at determined rates, depending on the drug and the condition.

With changes in place, and the Dextenza NDA resubmitted, Ocular Therapeutix believes it can receive approval for Dextenza, and, Corning says, it is “poised for success and future progress.”

For questions about this article, please contact Steve Lenier at Steve@stevelenier.com.