The FDA last week granted several pharmaceutical companies approval to market generic versions of the bestselling antipsychotic drug Abilify® (aripiprazole), despite the assertions of the drug’s patent-holder, the Japanese pharmaceutical company Otsuka, that the company remained entitled to orphan drug exclusivity for the drug. Otsuka maintained that the FDA’s approval of Abilify® for pediatric Tourette’s disorder precluded the approval of a generic for any uses while the exclusivity period for that specific use remained in effect. In an April 28, 2015, letter, however, the FDA rejected Otsuka’s contention. Instead, the FDA insisted that amendments to the Federal Drug and Cosmetics Act allow the Administration to approve applications for generics once the original exclusivity period of a drug expires. Moreover, even if a pharmaceutical company has been granted orphan drug exclusivity for certain uses – including pediatric uses – that exclusivity does not prevent the FDA from approving generic versions of the drug for its original uses. The FDA letter asserted that its administration harmonizes exclusivity provisions under the Hatch-Waxman Amendments and the Orphan Drug Act. Reading those provisions together, the FDA took the position that granting approval for a specific new use under the Orphan Drug Act does not necessarily extend a patent-holder’s period of exclusivity for the drug’s originally approved uses.

In this case, Otsuka enjoyed a five-year exclusivity period for Abilify® after the drug was first approved for schizophrenia, during which time Otsuka also sought and received approval to market the drug for pediatric Tourette’s Disorder. This new use entitled the manufacturer to three years of Hatch-Waxman exclusivity and seven years of orphan drug exclusivity for the specific use of the drug in the treatment of Tourette’s Disorder. When the original exclusivity term for Abilify® was expiring, Otsuka sought a decision from the FDA preventing other companies from marketing a generic on the basis that Abilify® was still entitled to exclusivity under the Orphan Drug Act and, because the FDA could not permit the omission – or carving out – of pediatric use information on labeling for uses protected by orphan drug exclusivity, the FDA was precluded from approving the marketing of generic versions of Abilify® until Otsuka’s orphan drug exclusivity period expires.

The FDA, however, rejected Otsuka’s interpretation of the Orphan Drug Act, explaining that it has long permitted labeling carve-outs to remove indications protected by unexpired orphan drug exclusivity in circumstances where omission of the label information specific to the orphan indication would not make the generic less safe and effective for the original approved indication. The Administration noted that, in certain situations, it has determined that generic labeling needed to retain pediatric information related to an indication protected by exclusivity where carving it out would present a safety risk to pediatric patients using the drug for its approved (non-protected adult) indication. According to the letter, pediatric information is required only when the use for which pediatric information is being omitted is the same as that approved for adults – which was not the case with Abilify®. The FDA determined as a factual matter that it was not necessary to retain in the generic drug labeling any information related to the drug’s protected Tourette’s Disorder use, and that the generic with the protected information carved out “remains safe and effective for all of the remaining non-protected conditions of use.” The FDA also concluded that there was no information remaining in the labeling describing the use of the generic in adults that would lead to an unsupported use of the generic in pediatric patients with Tourette’s Disorder.

According to the letter, the conclusion would remain the same even if the Tourette’s Disorder indication were protected only by orphan drug exclusivity. Abilify®’s labeling contains no information about the use of the drug for Tourette’s Disorder in adults. If the pediatric information related to Tourette’s Disorder is carved out for generic labeling purposes, the remaining labeling would not include any information on use of the drug to treat Tourette’s Disorder in adults, because this information is not included on Abilify®’s labeling.

The impact of the FDA’s decision is that several companies will be allowed to enter the market with generic aripiprazole, although the generics must carve out the use of the drug for treating pediatric Tourette’s Disorder from their labeling and marketing while the exclusivity period for that pediatric use remains in effect.