US gene therapy approvals create a big problem for Brazil. Regulators have to come together, FDA's Peter Marks says

If a gene therapy is approved in the U.S., patients in Brazil can sue their government to get it cleared for use there. And, when the million-dollar price tag is slapped onto the treatment and Brazilian patients can’t afford it, they can sue for that, too.

“This is a big problem. We are a low-income country, and we don't have a large budget,” said Francielli Melo, Ph.D., senior regulatory specialist and GMP inspector for cell and gene therapy at the Brazilian Health Regulatory Agency (Anvisa).

So, regulators around the world are struggling to keep up as companies begin to bring more potentially curative but very expensive treatments to the market in the U.S.

It’s why global regulators need to work together, the FDA’s Peter Marks, M.D., Ph.D., said at the American Society of Gene and Cell Therapy annual meeting Thursday in Baltimore.

Always an evangelist for lowering the cost to develop treatments via regulatory efficiency, Marks said that without regulatory convergence, bad actors around the world are pumping out treatments that do not work and administering them to patients.

“The problem is that with the different regulatory frameworks in different countries right now, it's one of these things where people just pick up and move from one place to another,” Marks said.

Medical tourism, where countries with lax regulatory standards approve treatments without regard for efficacy, has been a major issue for the FDA. Patients with difficult diseases travel to get access, spending tourism dollars, booking hotels and so on, so there’s an incentive for regulators to approve treatments. Marks said it’s like “whack a mole” trying to stop this, as another pops up as soon as they address one.

“When the people are vulnerable, they don't care about the regulation rules. They just have the access, and that’s so sad,” Melo said.

These patients often come back with complications and go to the FDA for help.

“Unfortunately, we really can’t do much in that situation but caution people,” Marks said.

Melo said that good regulation attracts good companies. Brazil has tried to help countries that reach out for help in crafting regulatory policy.

After the tough years of the pandemic, Marks said that the FDA staff has a little more wiggle room to work toward convergence. He suggested the global counterparts could get together and work on one central technical document to define regulatory needs, much like the FDA’s Oncology Center of Excellence has done with Project Orbis for high-income countries. His agency, the Center for Biologics Evaluation and Research, is working on a pilot program for gene therapy with the European Medicines Agency. 

“Modest differences in requirements for certain studies like toxicology studies or manufacturing information, it’s not helping rare disease patients in any right,” Marks said.

For companies looking to eventually bring a drug outside the U.S., Marks welcomed drug sponsors to bring a friend to their FDA meetings—specifically, a regulator from another country—so they can see the U.S. counterparts’ process and have confidence in an ultimate approval. The FDA is legally required to protect companies’ intellectual property, so the agency itself can’t make these invitations. But companies are welcome to.

There are some caveats to this. The regulator has to be one that the FDA has confidentiality agreements with, too, but Marks would like to see more sponsors using this to expedite approvals elsewhere in the world.

“We've done this now, and, [for] some sponsors, the feedback has generally been very positive, because other regulators hear what we're saying in real time, and it allows for alignment from an early place. I think it's an underutilized feature,” Marks said.

This strategy is not current about regulatory convergence at this stage, Marks noted. The bring-a-regulatory-friend strategy only began in the past couple of years and aims to be informational. But the option allows sponsors to be more prepared for conversations with other agencies.