From The Editor | July 11, 2024

Reading The Room In Oncology Drug Development

Ben Comer_2022_1

By Ben Comer, Chief Editor, Life Science Leader

Frank Bedu-Addo
Frank Bedu-Addo, Ph.D.

“Early and often” is the common refrain biopharmaceutical CEOs give to the question of how best to communicate with the FDA during drug development. The response is so common, and so engrained in the firmament of drug R&D, that clinical trial protocol or endpoint missteps identified by FDA — after a clinical trial has concluded, with data and results reported — can seem mystifying. Why, after all, would a drug developer spend millions of dollars on a clinical trial, only to find out later that the trial wasn’t designed in a way that the FDA would deem acceptable?

Individual and company experiences with the FDA can vary according to disease area, FDA reviewer, drug mechanism, and a host of other factors. What is most important, however, is that drug developers “understand the FDA’s perspective on any specific target indication, and what the FDA expects to see in order to be comfortable with an approval,” says Frank Bedu-Addo, Ph.D., CEO at PDS Biotech. To do that, early conversations with FDA are necessary. “We like to get [FDA’s] feedback and suggestions,” which the company takes into consideration. Then, says Bedu-Addo, it’s good to double confirm with the agency after designing the trial.

“We’ll go back to the FDA and say, ‘Does this incorporate what you were expecting? Are you good with this trial? If we run this trial and meet these endpoints, would you be comfortable approving this?’ That open dialogue with the FDA is very beneficial to us,” says Bedu-Addo.

Oral communication with the FDA is typically more enlightening than a written exchange, adds Bedu-Addo. “In our experience, when you have open and oral communication with the FDA, certain things ultimately come up that allow you to ask certain questions, which also allows the agency to really see your team having that discussion. It breeds familiarity, and helps the FDA understand who is working on the product and how it has been done.”

Oncologists In Your Corner

In oncology, where PDS Biotech’s internal drug development efforts are focused, it also can be beneficial to involve experts and KOLs in company discussions with FDA, for two key reasons.

First, although the FDA has its own oncology subject matter experts, it is advantageous to have oncologists on hand that can speak to their own direct experiences giving a product to patients, says Bedu-Addo.

Second, the FDA is extremely focused on the safety and tolerability of new products, for good reason. “Protecting patients is the FDA’s goal, and oncologists have the same goal … our market research shows that even though oncologists are looking for novel approaches to treating different cancers, they remain very concerned about patient safety.” Discussions between practicing oncologists with direct product experience, and FDA oncology subject matter experts, helps the agency “make an assessment of what the company is developing, and how it’s progressing.”

PDS Biotech’s lead development program is a triple combination product indicated for HPV16-positive head and neck squamous cell carcinoma (HNSCC). In preparing for a pivotal Phase 3 trial slated for later this year, PDS engaged with FDA and came away with a clear trial endpoint. “FDA made it very clear to us that in recurrent metastatic head and neck cancer, objective response rates or progression-free survival rates don’t necessarily translate to survival,” says Bedu-Addo. “The agency said our Phase 3 trial must be designed with overall survival as the primary endpoint.”          

Given the overall survival data generated to date in the PDS-sponsored VERSATILE-002 Phase 2 trial, as well as a National Cancer Institute-sponsored Phase 2 trial, Bedu-Addo is confident that the triple combination could add a year or more in overall survival to the current standard of care. Feedback from the FDA, which involved getting “an honest opinion on what the agency would expect to see [in the Phase 3 trial data] to be comfortable,” helps to form a clear goal everyone can work toward. “We are grateful for that opportunity, and for the FDA’s responsiveness,” says Bedu-Addo.

PDS is targeting 4Q 2024 for the Phase 3 trial start and is actively engaged in qualifying clinical sites and working with KOLs and potential investigators. The company is also awaiting a meeting with the FDA later this month, to go over the final Phase 3 protocol. As with marriage, communication is the key to a successful relationship with the FDA.