Strict regulations on drug safety and testing make it difficult to develop new treatments for rare, obscure and deadly diseases, according to experts. As the Orphan Drug Act turns 40, advocates want Congress and the Food and Drug Administration (FDA) to be more flexible when supporting the development of treatments and cures for rare diseases. 

“Quality and access are the two largest challenges for the next few years,” Thomas Crawford, a pediatric neurologist at Johns Hopkins Children’s Center, said. “There’s a need to modify and move the Orphan Drug Act into the next generation.”

Rare diseases are defined as those with fewer than 200,000 patients. There are estimated to be about 10,000 rare diseases impacting 30 million Americans, half of whom are children, according to the National Institute of Health (NIH).

The 1983 Orphan Drug Act provided a framework for developing treatments for these rare diseases through financial incentives for drug manufacturers and expedited approvals. Before the ODA, there were less than 40 treatments for rare diseases. Now there are over a thousand, but an estimated 90 percent of rare diseases still don’t have a treatment, advocates say.

“Rare diseases really aren’t that rare,” said Heidi Ross, vice president of policy at the National Association of Rare Disorders. “There are millions of Americans who are still holding out that chance and still want that opportunity to change the lives of their loved ones, to change the lives of themselves.”

Industry experts and patient advocates discussed the future of the ODA at an event hosted by The Hill on Tuesday to celebrate Rare Disease Day, the international day of advocacy for rare disease treatment. The event was sponsored by Alexion, the rare disease division of AstraZeneca, and moderated by The Hill’s Editor-in-chief, Bob Cusack.

Many of the barriers for rare disease treatment development are regulatory, Crawford and others said. When developing treatments, researchers are allowed to go outside of set guidelines in order to treat deadly cases of disease. However, there is no guidance from the FDA or Congress on how far they can or should go outside those guidelines, or what that may look like.

That makes it difficult for the FDA to approve treatments for rare diseases, which usually have less certainty in treatment outcomes, according to former FDA official Frank Sasinowski. Sasinowski helped implement the ODA while with the office, and has since worked as a rare disease advocate.

“It’s akin to being told that you as an FDA official should be allowed to color outside the lines, but we’re not going to tell you how far before you’ve gone too far. And we’re not going to tell you what colors you can use. It’s a terrible burden,” he said.

Some experts proposed the development of regulations corresponding to the size of the disease itself. A disease with fewer cases and a higher severity would perhaps be easier to approve a treatment for compared to one which is more common or less severe, for example.

“The idea that you can have one regulatory authority for a disease that affects two kids or 200,000 with the same metric of safety is crazy,” Crawford said. “It also has to do with cost because if the safety bar is so high, that means the costs are usually so high that (patients) can’t do it.”

But to do that, the FDA should look to patients, not Congress, Global Liver Institute founder Donna Cryer said. Cryer herself suffers from a rare form of liver disease, she said. She advocated for patient-focused drug development meetings, which has been used in limited cases by the FDA.

“Having patients set what is the right mark between the benefits, the safety and the efficacy of a particular treatment in the context of the disease … getting that directly from patients about what risk they are willing to take, frankly, is much more useful either to FDA than having the data all by themselves, and it’s certainly not something the legislature is qualified to do,” Cryer said.

One concern that some experts shared with Rep. Mariannette Miller-Meeks (R-Iowa) is the impact of the Inflation Reduction Act on rare disease treatment development. The portion of the IRA which regulates drug prices could lead to reduced industry revenue and to reduced investment in research, analysts say.

“I was very concerned about the provisions of the (Inflation Reduction Act), especially when it comes to rare and orphan diseases,” Miller-Meeks said following the panel. “Even a CEO admitted that there are drugs that will never come to the marketplace. We already know companies that are standing back from research and development, and that means research and development into diseases that are uncommon.”

Miller-Meeks said she hopes to see bipartisan support for rolling back that section of the IRA and she has seen some bipartisan support for expanding the use of telehealth and allowing generic production of drugs like insulin, she said.