FDA Ends Orphan Exclusivity for Octapharma Drug Wilate

From BioWorld Today (August 10, 2012)

Agency Admits Mistake

In an agency first, the FDA is rescinding an orphan drug exclusivity, saying it made a mistake two years ago in determining that Octapharma USA Inc.’s Wilate was superior to CSL Behring LLC’s previously approved Humate-P.

As a result, Wilate (von Willebrand Factor/Coagulation Factor VIII Complex) will keep its orphan drug designation, but it will lose its seven years of exclusivity. The decision is retroactive to December 2009, when the drug was approved to treat spontaneous and trauma-induced bleeding episodes in certain patients with von Willebrand disease.

Wednesday’s decision, which was a response to a citizen petition filed last year by Behring, shows that "exclusivity is not sacrosanct," Kurt Karst, a director at Hyman, Phelps & McNamara, told BioWorld Today.

But Octapharma begs to differ. In its response to Behring’s petition, Octapharma argued that, according to the Orphan Drug Amendments (ODA), a product granted orphan drug designation is entitled to exclusivity upon approval. It also claimed that the law includes no provision for revoking exclusivity, even though some lawmakers have tried to add such a provision over the years.

Those efforts have failed, Octapharma said, because they would weaken the incentives to develop orphan drugs. "To provide the necessary incentive, the process should be as certain as possible," the Hoboken, N.J.-based company said.

Tying exclusivity to the orphan drug designation, Octapharma said FDA regulations, in conflict with the ODA, allow for revocation only if the sponsor fails to provide sufficient quantities of the drug, the orphan drug designation was granted based on an untrue statement of material fact or the omission of material information, or if it’s determined the drug wasn’t eligible for the designation in the first place.

Since the FDA maintained that Wilate is still entitled to the orphan drug designation, Octapharma said the exclusivity cannot be revoked.

Under the ODA, a follow-on drug can only be granted orphan drug designation and exclusivity if it is superior to drugs previously approved for the orphan indication. Superiority may be measured in terms of safety, efficacy or major contributions to patient care, such as a change that improves administration, Karst said.

Orphan exclusivity based on clinical superiority is rare, he added, because it’s uncommon to see the same drug being developed for the same indication ?? unless it’s a generic.

But since Humate-P was approved as a biologic, the generic path wasn’t open for follow-ons. The only course available at the time was for Octapharma to take the biological license application route for Wilate. The possibility of exclusivity made the path more inviting.

In its decision this week, the FDA draws a broad, bright line between orphan designation and exclusivity. Whereas a plausible hypothesis of superiority is good enough to get orphan drug designation, that hypothesis must be proven to obtain exclusivity, the agency said.

While it determined that Wilate was the same drug as Humate-P, which was approved in 1999 and enjoyed seven years of orphan exclusivity, the FDA agreed that Octapharma had a plausible hypothesis for superior safety in that the manufacturing of Wilate involves two viral inactivation processes whereas the Humate manufacturing entailed only one. Thus, Wilate can keep its orphan drug designation based on that hypothesis.

However, in its re-evaluation of the drug, the agency decided that the available data don’t "support a conclusion that Wilate has been demonstrated ‘to provide a significant therapeutic advantage over and above that provided’ by Humate." Consequently, the FDA said it was wrong in granting the exclusivity in the first place, and it’s now correcting that error.

Not the First Error

It’s not the first mistake the agency has made in connection with Wilate’s exclusivity. When the FDA approved Wilate in 2009, it erroneously informed Octapharma that it qualified for the seven-year orphan drug exclusivity because it was the first sponsor to get marketing approval for that drug in that indication.

The FDA backpedalled when it realized its error and told the company the only way it could get the exclusivity was if it demonstrated clinical superiority. Six months later, after reviewing data Octapharma submitted, the agency granted the exclusivity retroactive to the drug’s approval.

In rescinding that exclusivity, the FDA shot down Octapharma’s argument that it has a constitutionally protected interest in the exclusivity. Based on that interest, the drug maker claimed the FDA couldn’t revoke the exclusivity without due notice and a formal hearing process. The agency countered that the ODA provides no property rights to exclusivity. And if a company doesn’t agree with the agency’s decision, it has two options ?? file a citizen petition or take the FDA to court.

While Octapharma will lose the most under the FDA’s decision, Behring didn’t get everything it asked for in its petition. The agency denied the King of Prussia, Pa.-based company’s request to require head-to-head comparative clinical evidence of superiority in future orphan designation and exclusivity evaluations.

Rather than "prescribing the precise type and amount of evidence necessary," the FDA said it will continue with its case-by-case approach in determining what information is needed to demonstrate clinical superiority. That approach was laid out last year in the agency’s proposed amendments to its orphan drug regulations. (See BioWorld Today, Oct. 19, 2011.)
 

Posted: August 2012


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