According to experts, strict rules of drug safety and testing complicate the development of new methods of treatment for rare, obscure and deadly diseases. As the Orphan Drug Act turns 40, supporters want Congress and the Food and Drug Administration (FDA) to show more flexibility in supporting the development of treatments for rare diseases.

“Quality and access are the two biggest challenges for the next few years,” said Thomas Crawford, a pediatric neurologist at Johns Hopkins Children’s Center. “The Orphan Drug Act needs to be changed and carried forward into the next generation.”

Rare diseases are defined as those that affect fewer than 200,000 patients. There are an estimated 10,000 rare diseases that affect 30 million Americans, half of whom are children. National Institute of Health (NIH).

The Orphan Drug Act of 1983 provided a framework for the development of treatments for these rare diseases through financial incentives for drug manufacturers and accelerated approval. Before the ODA, there were fewer than 40 treatments for rare diseases. Now there are more than a thousand of them, but according to estimates, about 90 percent of rare diseases are still incurable, human rights activists say.

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

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

Many of the barriers to developing treatments for rare diseases are regulatory, Crawford and others said. When developing treatments, researchers are allowed to go beyond established guidelines to treat fatal cases of the disease. However, there is no guidance from the FDA or Congress on how far they can or should go beyond these guidelines, or what that might look like.

According to former FDA official Frank Sasinowski, this makes it more difficult for the FDA to approve treatments for rare diseases, which typically have less certainty about treatment outcomes. Sasinowski helped implement the ODA while in office and has worked as a rare disease advocate ever since.

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

Some specialists suggested to develop standards corresponding to the size of the disease itself. A disease with fewer cases and a higher severity might be easier to approve for treatment compared to a more common or less severe one, e.g.

“The idea that you can have one regulatory body for a disease that affects two children or 200,000 with the same safety profile is crazy,” Crawford said. “It’s also about cost, because if the safety bar is that 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, said Donna Cryer, founder of the Global Liver Institute. Cryer herself suffers from a rare form of liver disease, she said. She advocated for patient-centered drug development meetings, which have been used in limited cases by the FDA.

“When patients make the right trade-off between the benefits, safety, and efficacy of a particular treatment in the context of a disease … getting information directly from patients about what risk they’re willing to take is, frankly, much more useful or to the FDA than having the data on its own , and that’s certainly not what the Legislature has the power to do,” Cryer said.

One of the concerns some experts have shared with Rep. Marianette Miller-Meeks (R-Iowa) is the impact of the Inflation Reduction Act on the development of treatments for rare diseases. Part of the IRA, which regulates drug prices, could lead to lower industry revenues and 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 after the debate. “Even the CEO has admitted that there are drugs that will never make it to market. We already know companies that are giving up research and development, which means research and development for diseases that are rare.”

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

According to experts, strict rules of drug safety and testing complicate the development of new methods of treatment for rare, obscure and deadly diseases. As the Orphan Drug Act turns 40, supporters want Congress and the Food and Drug Administration (FDA) to show more flexibility in supporting the development of treatments for rare diseases.

“Quality and access are the two biggest challenges for the next few years,” said Thomas Crawford, a pediatric neurologist at Johns Hopkins Children’s Center. “The Orphan Drug Act needs to be changed and carried forward into the next generation.”

Rare diseases are defined as those that affect fewer than 200,000 patients. There are an estimated 10,000 rare diseases that affect 30 million Americans, half of whom are children. National Institute of Health (NIH).

The Orphan Drug Act of 1983 provided a framework for the development of treatments for these rare diseases through financial incentives for drug manufacturers and accelerated approval. Before the ODA, there were fewer than 40 treatments for rare diseases. Now there are more than a thousand of them, but according to estimates, about 90 percent of rare diseases are still incurable, human rights activists say.

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

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

Many of the barriers to developing treatments for rare diseases are regulatory, Crawford and others said. When developing treatments, researchers are allowed to go beyond established guidelines to treat fatal cases of the disease. However, there is no guidance from the FDA or Congress on how far they can or should go beyond these guidelines, or what that might look like.

According to former FDA official Frank Sasinowski, this makes it more difficult for the FDA to approve treatments for rare diseases, which typically have less certainty about treatment outcomes. Sasinowski helped implement the ODA while in office and has worked as a rare disease advocate ever since.

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

Some specialists suggested to develop standards corresponding to the size of the disease itself. A disease with fewer cases and a higher severity might be easier to approve for treatment compared to a more common or less severe one, e.g.

“The idea that you can have one regulatory body for a disease that affects two children or 200,000 with the same safety profile is crazy,” Crawford said. “It’s also about cost, because if the safety bar is that 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, said Donna Cryer, founder of the Global Liver Institute. Cryer herself suffers from a rare form of liver disease, she said. She advocated for patient-centered drug development meetings, which have been used in limited cases by the FDA.

“When patients make the right trade-off between the benefits, safety, and efficacy of a particular treatment in the context of a disease … getting information directly from patients about what risk they’re willing to take is, frankly, much more useful or to the FDA than having the data on its own , and that’s certainly not what the Legislature has the power to do,” Cryer said.

One of the concerns some experts have shared with Rep. Marianette Miller-Meeks (R-Iowa) is the impact of the Inflation Reduction Act on the development of treatments for rare diseases. Part of the IRA, which regulates drug prices, could lead to lower industry revenues and 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 after the debate. “Even the CEO has admitted that there are drugs that will never make it to market. We already know companies that are giving up research and development, which means research and development for diseases that are rare.”

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