Regulatory Focus™ > News Articles > Orphan Drug Marketing Exclusivity Revoked from Product as FDA Admits Error

Orphan Drug Marketing Exclusivity Revoked from Product as FDA Admits Error

Posted 10 August 2012 | By Alexander Gaffney, RAC 

In a groundbreaking move, the US Food and Drug Administration (FDA) moved to rescind marketing exclusivity for an orphan drug product manufactured by OctaPharma used for the treatment of von WIllebrand disease (VWD), a hereditary bleeding disorder.

OctaPharma's VWF drug Wilate, a Factor VIII concentrate, received approval from FDA on 30 November 2009 for the treatment of severe VWF and mild to moderate VWF in patients where an existing therapy, desmopressin, proved ineffective.

In approving OctaPharma's Biologics License Application (BLA) for the drug, FDA noted VWF affects approximately 1-2% of the US population and granted an orphan designation for the product. Under the terms of the designation, OctaPharma would retain an exclusive designation Factor VIII to treat VWF for seven years, during which time other drugs could not compete for the same condition based on "hypothetical" superiority.

Insufficient Evidence to Support Exclusivity

Enter: CSLB Behring.

In a 25 March 2011 Citizen Petition to FDA, CSLB President Peter Turner requested the agency revoke Wilate's marketing exclusivity because its application, "Did not include sufficient evidence to demonstrate that Wilate is superior in safety to the same drug previously approved for the same orphan indication."

FDA had incorrectly found Wilate to offer superior viral safety than CSLB's Humate-P-basically the exact same drug-wrote Turner. Humate-P had been approved by FDA in 1999, also with an orphan drug designation, and its exclusivity license expired in 2006. Shortly thereafter, OctaPharma submitted its BLA to FDA stating Wilate exhibited a, "Significant improvement in safety or effectiveness over existing products." In other words, OctaPharma claimed Wilate was superior to Humate-P based on its manufacturing processes allowing it to produce a purer, virus-inactive product.

CSLB explained in its Citizen Petition that this hypothetical exclusivity was never adequately determined, and in fact OctaPharma's product was potentially more dangerous than Humate-P based on an adverse event signal indicating a risk of "thromboembolic phenomenon." In a 23 September 2011 letter to FDA, OctaPharma strongly disputed this claim, saying no reported cases had been brought to its attention since its approval in more than 49 countries.

CSLB further contended FDA never should have granted OctaPharma's orphan drug designation because it offered neither a substantial increase in safety for the most frequent adverse effects nor a major contribution to patient care.

OctaPharma dismissed CSLB's claims in its own Citizen Petition to FDA, saying CSLB's petition, "Adds no new information to what has been known since 2006, and there is no reason for FDA to change its position."

FDA: We Acknowledge Our Error

In an 8 August 2012 response to CSLB's Citizen Petition, FDA agreed with both CSLB's request and general claims.

The agency said, "A re-evaluation of the administrative record has shown that available data do not support a conclusion that Wilate has been demonstrated to 'provide a significant therapeutic advantage over and above that provided by' Humate."

"Wilate should not have been found to be eligible for orphan drug exclusivity because it is not clinically superior to, and hence is the same drug as, a previously approved drug (Humate) under the orphan drug regulations," FDA continued. "FDA acknowledges its error in determining that Wilate is clinically superior to Humate within the meaning of the orphan drug regulations and grants your request to rescind Wilate's orphan drug exclusivity."

In particular, FDA said it erred when it found OctaPharma's manufacturing processes superior to CLSB's. "A comparison of the cumulative viral clearance outcomes of all relevant manufacturing steps in fact shows that these two products achieve similar levels of viral safety," explained FDA. "FDA now concludes that the global viral clearance data are insufficient to establish that the WIlate manufacturing process confers 'a significant therapeutic advantage' over the manufacturing process used in Humate."

A Precedent-Setting Decision

FDA said it would continue to allow OctaPharma's product to be marketed under the orphan drug designation, but that it would lose its marketing exclusivity rights.

OctaPharma said in its 2011 Petition that its constitutional rights were bring infringed upon by denying it its due process rights. Not so, said FDA. Under FDA's understanding, OctaPharma has no grounds to contest FDA's finding as it has, "No property right in its orphan drug exclusivity that would entitle it to the sort of process to which OctaPharma claims it is entitled."

Even if OctaPharma had such a right, explained FDA, the Citizen Petition process allows such views to be aired and heard in a way that satisfies those same rights.

FDA noted this is the first time it has ever revoked a company's marketing exclusivity for an orphan drug product, which raised some novel arguments from OctaPharma, including that FDA did not have the authority to revisit such a decision. FDA disagreed, stating, "This is simply not true."

"Courts have upheld FDA's inherent recission authority," added FDA. "Indeed, courts have recognized that agencies, including FDA, have a duty to correct their errors. Moreover, we are not aware of any authority suggesting that FDA should not correct its error merely because FDA has never previously corrected an erroneous orphan drug exclusivity determination by rescinding it … and we reject that suggestion."

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