DDF 2018: Approaching accelerated approvals in multiple markets

“We have seen tremendous liberalization in the U.S. aimed at getting breakthrough drugs to patients very rapidly,” said Roy Baynes, a senior vice president and head of clinical development at Merck. “This is in every version, such as breakthrough designation and accelerated approval, and the ability to have what’s now called real-time review of data.”

Many regions have tried to follow the U.S.’ example, including Japan, which has introduced initiatives such as an equivalent to an early-access approach, and China, which has evolved at “warp speed.” Meanwhile, Baynes said, Europe is lagging.

The keynote panel at this year’s Drug Development Forum discussed the pursuit of breakthrough approvals in multiple global markets. Martine Zimmerman, Alexion’s senior vice president of global regulatory affairs, pushed back on Baynes’ comments with “Do we agree Europe is lagging behind? It’s different, right?”

She pointed to an EMA-specific process in which companies can meet with the agency and payers to get feedback on what payers expect from the data.

“This is something I would encourage very much. Looking at this from this side of the pond, it may be seen as slowing down development because it’s difficult to schedule.” Sometimes, she added, companies think they know better and press ahead in the way they think best, with plans to react to EMA and payer feedback, rather than approaching it proactively.

In addition to navigating relationships with various regulatory agencies, the disparate approaches across regions also place different evidentiary expectations on companies trying to develop drugs for a small to midsize patient population, said Ramzi Dagher, vice president of worldwide safety and regulatory, and regulatory head of Europe and international at Pfizer.

“In many markets—Asia and Latin America, especially—historically, for many reasons, the national authorities have required that your clinical trial footprint includes a specific number or threshold of patients from that region or from that country,” he said. This can become challenging if you’re dealing with a relatively rare disease: “If you have 20 markets and each of them wants 300 patients in a trial, … that’s not going to work.”

Some companies, including Pfizer, are working on a more holistic approach to tackle these issues on a wider, if not global, scale.

Audience members posed a pair of timely questions, one about companies’ plans to cope with Brexit and a second about the “right to try” legislation passed this year.

The panelists agreed that the best form of access to medicine was through an approved, reimbursed drug. Making them available to patients before they have been approved could make sense in some situations—if you’re on the path to registration, said Iovance CEO Maria Fardis, Ph.D., and if the estimated benefits indeed outweigh the risks, said Baynes. Iovance has been directing patients requesting to try its experimental treatments to academic institutions that are running studies, as it has no safety data at all for certain populations, such as pediatric patients, said Fardis.

The short answer to the Brexit question was “we don’t know.” Companies are planning for a so-called hard Brexit, Zimmerman said. Those importing into Europe via the U.K. are stockpiling products and making sure there is a Qualified Person based in the EU to release those products, she said.

As for the U.K., Baynes believes that however Brexit ultimately unrolls, somebody will be there to make sure patients in the U.K. get the medicines they need.