For years, discussions of retina drug development have centered on mechanisms of action, durability, and clinical outcomes. During the Retina Innovation Summit in Montreal, however, an afternoon conversation focused on something less visible: the regulatory strategy that determines how new therapies ultimately reach patients.
During a panel moderated by Pravin U. Dugel, MD, of Ocular Therapeutix, regulatory experts, drug development leaders, academic advisors, and healthcare investors discussed how recent FDA guidance may be changing expectations for ophthalmic clinical development. Although panelists broadly agreed that regulatory planning now plays a larger role than ever before, they differed on how sponsors should interpret the agency’s evolving approach.
Among the most discussed topics was the FDA's position on sham controls in intravitreal injection studies. Arthur A. Ciociola, Ocular’s chief regulatory and quality officer, said years of agency experience have led regulators to recognize that patients often know whether they received an injection, potentially introducing bias into masked studies. He pointed to public comments from current and former FDA officials suggesting that “sham controls are not recommended” and said that ongoing studies using sham controls ultimately may be evaluated differently depending on their design.
Ciociola also highlighted the FDA's guidance describing circumstances in which a single adequate and well-controlled trial, supported by confirmatory evidence, may establish substantial evidence of effectiveness. Rather than representing a wholesale policy change, he characterized the guidance as a clarification and expansion of existing regulatory principles that sponsors preparing for pivotal studies should understand. "You should take a look at this guidance," he advised. “It’s of great value.”
An emphasis on the quality of clinical evidence carried through the remainder of the discussion. Snehal Shah, PharmD, president of research and development at Oculis, argued that sponsors should prioritize collecting the minimum amount of high-quality data needed to answer clinically meaningful regulatory questions instead of simply generating larger data sets. “We’ve got to bring [therapeutics] to patients as quickly and as efficiently as possible, but we cannot sacrifice data quality,” Shah said. The goal, he added, is “not more data, but better data.”
Dr. Shah described patient-centered trial design, Quality by Design principles that emphasize collecting clinically meaningful evidence, and early engagement with the FDA through Special Protocol Assessments (SPAs) as important tools for reducing regulatory risk and maintaining disciplined development programs.
Looking beyond regulatory interactions alone, Adrienne L. Graves, PhD, an independent director for public and private biotechnology and pharmaceutical companies, chair of the RD Fund, former president and CEO of Santen, and former board chairman of Iveric Bio, urged companies to begin planning for commercialization well before approval. That includes engaging regulators, payers, manufacturing teams, and physician stakeholders early while designing studies around outcomes meaningful to patients, including improved vision and reduced treatment burden.
The conversation shifted when the panel turned to the investment community. Rael Mazansky, MD, MBA, managing director of Deep Track Capital, described the challenges investors face when evaluating companies developing long-acting retinal therapies under evolving FDA guidance. Public statements from agency officials, sponsor interactions with regulators, and written guidance do not always provide complete clarity, he said, requiring investors to piece together how individual development programs ultimately may be judged.
Anupam Dalal, chief investment officer and managing member of Acuta Capital Partners, agreed that greater regulatory flexibility creates new opportunities but argued that it also increases uncertainty. As more sponsors explore streamlined development strategies, he said, the critical question is no longer simply whether a study is adequate and well controlled, but whether the overall evidence package will prove sufficiently persuasive to support approval.
The discussion concluded without complete agreement on how the FDA's evolving framework should be interpreted. Ciociola and Shah maintained that early engagement with the agency and carefully constructed evidence packages can help position sponsors for success, and Dalal cautioned that flexibility in the regulatory framework should not be mistaken for a lower evidentiary bar.
Despite their differences, panelists agreed that regulatory strategy has become inseparable from scientific strategy. After opening with the observation that regulatory experts have become “the most important people in the company,” Dr. Dugel closed the panel with a practical recommendation for drug developers: “Please engage the FDA right away and throughout your development.” RP