FDA remains silent on orphan drug exclusivity after last year's court loss

 Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

“These sponsors cannot even be certain that their orphan-designated products will be protected by orphan exclusivity, because FDA’s OOPD has effectively stopped making exclusivity determinations since late 2021. The agency appears to be seeking to avoid having to recognize an orphan exclusivity broader than a product’s approved use, as the Catalyst decision would seem to require of FDA,” O’Brien wrote yesterday.

The FDA said in an emailed statement that FDA “is not currently finalizing ODE [orphan drug exclusivity] determinations” because of the “far-reaching implications” of the court’s decision. The agency added:

The decision has caused uncertainty for rare disease drug development. Under the court’s interpretation of the scope of ODE, ODE would block approval of another company’s application for the same drug for the entire disease or condition for which the drug is granted orphan-drug designation, regardless of whether the drug was approved only for a narrower use or indication.  Under that interpretation, a sponsor could seek approval and exclusivity for a drug by focusing on the smallest, easiest-to-study populations and such exclusivity would block the drug for the entire disease, even though the sponsor did not invest in studying and developing the drug for all individuals with the disease. This could adversely affect children—particularly the youngest pediatric populations—and other populations that are typically studied later in drug development.

What’s unique about this situation, O’Brien told Endpoints News in a phone interview, is that any congressional fix would have to be retroactive. And if there isn’t a congressional fix in the near term, “this is really going to snowball and force FDA’s hand” as any second-in-line competitors for a novel product could seek approval for a different subset of the same disease, essentially dividing up the disease and winning exclusivity for all subsets if Catalyst remains the law.

“It’s pretty unusual for FDA to try to un-ring the bell, and go back to recodify an interpretation,” O’Brien added.

The agency made clear last May that the court’s decision would have a profound impact on rare disease drug development and in the way it assesses exclusivity as it “blocks approval of another company’s application for the same drug for the entire disease or condition for which the drug is granted orphan-drug designation, regardless of whether the drug was approved only for a narrower use or indication.”

The agency even went so far as to lobby Congress on the issue, seeking a permanent resolution, but to no avail yet.

Orphan exclusivity is granted to drugs designated and approved to treat diseases or conditions affecting fewer than 200,000 people in the US (or more than 200,000 and no hope of recovering costs).

O’Brien said his pharma clients are confident that if an approval is a first-ever approval, the exclusivity will be there down the road, but there are “still some frustrations” particularly as the Inflation Reduction Act exempts drugs from Medicare negotiations if they have only one orphan indication, so some sponsors may also be worried about losing that exemption.

He also said he thought FDA could grant the exclusivity and put the dates down in its database because Catalyst “is about scope of exclusivity, not eligibility for earning it.”

The Catalyst case in question from last October saw a US appeals court overturn a prior FDA court win, saying that the agency never should’ve approved a rare disease drug because a previously approved but more expensive drug with the same active ingredient has orphan drug exclusivity barring such an approval.

After asking the Supreme Court to review the case, the two companies announced a settlement in July, whereby Jacobus agreed to withdraw its petition to SCOTUS and Catalyst dismissed its patent infringement claims and acquired rights to distribute Jacobus’ Ruzurgi in the US as a treatment for the rare Lambert-Eaton myasthenic syndrome in pediatric patients.

“As a result, the outcome that FDA appears to have sought to avoid — a single approved amifampridine product on the market — remains the status quo, at least until the expiration of the seven-year orphan exclusivity period for Catalyst’s Firdapse in November 2025,” O’Brien wrote.

In the coming months, Congress will either need to pass a long-term fix for all orphan indications, or the FDA will need to finally consider how the court’s flip affects drugs with active terms of orphan drug exclusivity as well as currently marketed drugs, including generics.

The FDA previously said it expects that some drugs that are in late-stage development, or that have already been submitted for marketing application review, would be blocked from approval under the Catalyst decision’s interpretation of the Orphan Drug Act.

“The agency could also consider opening a public docket to solicit stakeholder feedback on proposed resolutions, should a legislative fix not arrive soon,” O’Brien wrote, adding:

In the meantime, we recommend that sponsors carefully assess whether a competitor is likely to seek approval for the indication or use whose orphan exclusivity has not yet been recognized by FDA. In that situation, consideration should be given to a more assertive approach, including petitioning FDA to award the orphan exclusivity or preparing for potential litigation prior to a competitor approval.

Synlogic president and CEO Aoife Brennan received an orphan drug designation today for its potential treatment of homocystinuria, a rare metabolic disease, telling Endpoints via email:

The Orphan Drug Designation makes a real and critical difference for life sciences companies – especially development stage companies – attempting to tackle serious medical needs that affect smaller populations. With Orphan Drug Designation the opportunities for more open dialogue with the FDA during the development and registration process, tax benefits and fee waivers are material and can affect investment decisions in areas of significant medical need. We support any actions that will continue to bring access to Orphan Drug designation for eligible companies to help them advance programs.

https://endpts.com/fda-remains-silent-on-orphan-drug-exclusivity-after-last-years-court-loss/