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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.


The company stopped marketing Subutex tablets in 2011 but earned FDA approval for Sublocade in 2017.

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.

  • As a recovering addict I find this terrible we are in a crisis we need to be able to pull together as a nation and to be able to use all the resources we have. Them using the orphan act and blocking other companies from marketing other meds that could save lives is preposterous. I hate that everything is all about money and politics, I guess unfortunately that’s the world we live in. It breaks my heart.

  • I been working in the drug and alcohol field for many years. Now is not the time for bullshit. We have lost a hugh portion of a generation out there, due to opiate (heroin)addiction.Here is more food for thought, we have another generation growing up without parents.

  • I am an RN of 38 years. I agree with every word of this article. I work for a very large insurance company and despise this loophole. It prevent our patients from having access to other drugs. The loophole should be closed immediately.

  • The article mistakenly confuses “orphan drug designation” with “orphan drug exclusivity” (and also uses the term “orphan drug status” ambiguously). Orphan drug DESIGNATION is a special status given to a sponsor that confers special development benefits. Orphan drug EXCLUSIVITY is a period of marketing exclusivity that is granted for seven years following approval. The FDA Reauthorization Act of 2017 amended the Orphan Drug Act such that orphan drug designation no longer automatically confers exclusivity; there needs to be a finding of superiority to previous drugs. Therefore, it is misleading for the article to state that “along with that designation comes seven years of exclusivity.”

  • Your comment about exclusivity isn’t entirely accurate and is misleading. Specifically “the Orphan Drug Act of 1983 grants 7 years of market exclusivity for products to treat rare diseases and conditions affecting fewer than 200,000 patients in the US. Available for both drugs and biologics, Orphan Drug exclusivity does not merely defer the use of an abbreviated approval pathway (ANDA). It entirely prohibits approval of another application ‘for such drug for such disease or condition’ for 7 years after the initial product approval, even if the later applicant conducts its own clinical trials. IT DOES NOT, HOWEVER, PRECLUDE APPROVAL OF EITHER (1) ANOTHER DRUG FOR THE SAME DISEASE OR CONDITION OR (2) THE SAME DRUG FOR ANOTHER DISEASE OR CONDITION.” Thus, your statement that “This would prevent other drugs for opioid use disorder from being marketed, even though effective alternative drugs are available, and discourage the development of new ones.” is false.

    • The statute reads:

      Ҥ316.31 Scope of orphan-drug exclusive approval.
      (a) FDA may approve a sponsor’s marketing application for a designated orphan drug for use in the rare disease or condition for which the drug was designated, or for select indication(s) or use(s) within the rare disease or condition for which the drug was designated. Unless FDA previously approved the same drug for the same use or indication, FDA WILL NOT APPROVE ANOTHER SPONSOR’S MARKETING APPLICATION FOR THE SAME DRUG FOR THE SAME USE OR INDICATION before the expiration of 7 years from the date of such approval as stated in the approval letter from FDA, except that such a marketing application can be approved sooner if, and at such time as, any of the following occurs: . . . . “

  • Just as companies shouldn’t game the system; neither should the FDA under pressure from Bernie Sanders. FDA just approved a drug for Jacobus Pharmaceuticals for Lambert-Eaton Myasthenic Syndrome for pediatric use (without clinical studies in children) nearly immediately after approving the same drug for Catalyst Pharmaceuticals and following a rant by Sanders that the price of the Catalyst drug was too high. (Both were granted Orphan Drug status) Thus encouraging Jacobus to market it at a lower price and encouraging physicians to prescribe it off-label. The net result will force Catalyst to lower its price and consequently prevent scheduled clinical trials of the drug for another orphan indication. FDA is gaming the system under political pressure, knowing full well that Jacobus cannot complete the ordered post-marketing requirements with revenue from the pediatric patients for which it is approved. This action by FDA will damage the Orphan Drug Act more severely than the Indivior action because the FDA has now decided that it can deny exclusivity of orphan products on the whim of one politician running for president.

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