The 30 million Americans with rare diseases should feel as encouraged as I am by the ongoing and enthusiastic commitment the Food and Drug Administration has made to advancing the approval of orphan drugs. But a loophole exploited by a pharmaceutical company threatens the integrity of this vital act.
Over the past few years, fully one-third of new drugs approved by the FDA have been for rare diseases. The total number of orphan indications approved by the FDA jumped from 594 in 2016 to more than 770 in 2018. These approvals reflect not just a commitment by the FDA but also the success of the Orphan Drug Act, passed by Congress in 1983 to provide incentives for companies to develop orphan drugs. The act gives companies seven years of exclusivity for drugs given an orphan indication, a 25% tax credit for qualified clinical trials, and the waiver of application fees.
To be sure, more than 90% of the 7,000 rare diseases identified so far don’t have any FDA-approved treatments. And insurers, whether private or government-financed, are increasingly making it more challenging for patients to access orphan drugs that often have high prices. The challenges of access will likely become more acute as gene therapy — products that alter a patient’s genetic makeup and cure disease — become more available.
The loophole has to do with a drug called buprenorphine that is used to treat opioid use disorder. It controls cravings for opioids like heroin. A once-a-month injectable form of buprenorphine, sold under the name Sublocade, is a revised version of an earlier buprenorphine-based drug called Subutex.
Back in 1994, the FDA granted Subutex orphan drug status even though opioid addiction isn’t a rare disease. Instead, the drug’s maker, Indivior, based its application on a rarely used provision in the Orphan Drug Act that permits orphan drug designation when a manufacturer can show that a drug is unlikely to be profitable and so it will not recover its development costs.
According to FDA policy, orphan drug designation is automatically granted to later products from the same manufacturer that contain the same ingredient if it is shown to be superior to previously approved drugs containing the same ingredient. And along with that designation comes seven years of exclusivity.
Here’s the loophole: the second time around, the manufacturer of the drug’s new version doesn’t have to demonstrate an inability to recoup its development costs.
That doesn’t make sense on two levels. First, Sublocade and Indivior’s previous buprenorphine product have racked up sales of more than $10 billion and the company has made millions in profit since 1994 — with more profits to come if the FDA grants Sublocade orphan drug exclusivity. Second, an estimated 2.1 million Americans have an opioid use disorder, making it anything but an orphan disease.
Granting Sublocade orphan drug exclusivity would enable Indivior to market it without competition for seven years from its approval date. This would prevent other drugs for opioid use disorder from being marketed until the end of 2024, even though effective alternative drugs are available, and discourage the development of new ones.
This charade came to light when Braeburn, a pharmaceutical company that has received tentative FDA approval for a competing buprenorphine-based drug for opioid use disorder, filed a citizen petition asking the FDA to revoke orphan designation for Sublocade.
This is one more example of drug manufacturers gaming the system and undermining the Orphan Drug Act. The recently departed FDA commissioner, Scott Gottlieb, railed against such gaming of the system that enables manufacturers to make unreasonable profits.
Allowing Sublocade to continue being an orphan drug clearly subverts the intent and integrity of the 1983 Orphan Drug Act. This case is especially egregious because it involves a drug to treat the serious problem of opioid use disorder that is ravaging parts of the United States. Alternate treatments are needed for this disorder, but will be kept off the market by gaming the Orphan Drug Act.
I spent my career as an advocate for patients with rare diseases and have been a strong supporter of the Orphan Drug Act. I believe that the FDA should revoke the orphan designation for Sublocade. In the face of an epidemic of opioid addiction, which President Trump has identified as an emergency, the FDA has a clear and overwhelming public health obligation to enable safe and effective alternative treatments to become available. It also has an obligation to protect the integrity of one of the most successful health laws ever passed.
I agree with Gottlieb that gaming of the law undermines its integrity. Unless the FDA revokes this orphan drug designation, it is standing in the way of bringing to the market other drugs that can give people who are addicted to opioids effective treatments This flies in the face of the current administration’s dual commitments to reduce drug prices and to aggressively address the opioid addiction crisis.
The FDA should be helping get more anti-opioid treatments on the market, and not allowing the Orphan Drug Act to be misused. How it decides on the citizen petition will say a lot about the FDA’s commitment to the integrity of the Orphan Drug Act.
Diane Dorman served for 15 years as vice president for public policy of the National Organization for Rare Disorders, which represents patients and patient organizations with rare diseases.