[author: Larissa Bergin]
On April 13, 2015, the U.S. District Court for the District of Maryland issued an Order granting Otsuka Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Development and Commercialization, Inc., and Otsuka America Pharmaceutical, Inc.’s (collectively “Otsuka’s”) Motion to Stay the Proceedings and Memorandum in Support. The Order also grants Otsuka leave to amend its complaint, which calls into question whether FDA can implicitly encourage generic entry of a branded drug within previously-approved indications after it grants the same branded drug an orphan disease designation in the pediatric population. The Order denies as moot Otsuka’s Motion for Summary Judgment and defendants’ Motion to Dismiss for Failure to State a Claim, and, instead, grants Otsuka’s request to file for a temporary restraining order or a preliminary injunction against the FDA by April 15, 2015. Presumably, Otsuka will request injunctive relief prohibiting approval of abbreviated new drug applications (“ANDAs”) for generic versions of Abilify® (aripiprazole) now that the FDA has approved Abilify® for the narrow indication of the treatment of pediatric patients with Tourette’s Disorder. In the interim, the Court ordered the FDA to provide the Court with an Ex Parte Report at least twenty-four (24) hours prior to FDA’s decision to either approve or reject ANDAs for generic versions of Abilify®, as well as FDA’s decision with respect to Otsuka’s claimed entitlement to exclusivity.
The Orphan Drug Act (“ODA”) is designed to incentivize pharmaceutical companies to develop drugs that treat persons with a disease or condition that affects less than 200,000 persons in the United States (“orphan disease or condition”). The ODA provides seven years of marketing exclusivity for approval of indications that meet this definition, following granting an orphan drug designation for the same indication. In theory, the seven-year exclusivity period provides pharmaceutical companies an opportunity to recoup the cost of developing orphan drug indications for drugs that otherwise would not have such indications developed. A drug approved by FDA for such an indication is called an orphan drug. However, a pharmaceutical that recently received approval for a somewhat broader indication than the one proposed in its granted orphan drug designation has now raised two important questions regarding the FDA’s orphan drug approval process: 1) whether the FDA can grant broader approval than what is identified by the sponsor on the drug application and 2) whether generic entry is impossible for any given indication of a branded drug when orphan drug exclusivity is provided only for a pediatric indication of that same drug.
Otsuka filed a complaint against the FDA alleging violations of the Administrative Procedure Act (“APA”) and the Food, Drug, and Cosmetic Act (“FD&C Act”) because the FDA granted a broader indication for the drug Abilify than Otsuka applied for in its supplemental New Drug Application (“sNDA”) application. Otsuka alleged that its sNDA application was tailored to the narrow indication of the treatment of pediatric patients with Tourette’s Disorder. In 2006, the FDA granted orphan drug designation for the use of Abilify® for the treatment of Tourette’s syndrome. However, in 2014, Otsuka’s sNDA sought additional approval for the narrow indication of the treatment of pediatric patients with Tourette’s Disorder, which would have designated Ability® as an orphan drug for that exclusive indication. Thus, Otsuka conducted studies only on pediatric patients and revised its labeling accordingly for purposes of the sNDA.
On December 12, 2014, the FDA approved Otsuka’s sNDA and updated the Orphan Drug Designation and Approvals database. Upon approval, Otsuka allegedly contacted the FDA, stating that the FDA “was precluded from approving an ANDA for a generic version of Abilify® for any indication pending the expiration of Otsuka’s statutory seven year period.” (emphasis added). Otsuka’s logic was premised on its interpretation of Section 505A(o) of the Best Pharmaceuticals for Children’s Act (“BPCA”). Section 505A(o) of the BPCA pertains to drug labeling. The applicable part of the statute reads:
(1) General rule – A drug for which an application has been submitted or approved under section 355(j) of this title shall not be considered ineligible for approval under that section or misbranded under section 352 of this title on the basis that the labeling of the drug omits a pediatric indication or any other aspect of labeling pertaining to pediatric use when the omitted indication or other aspect is protected by patent or by exclusivity under clause (iii) or (iv) of section 355(j)(5)(F) of this title.
(2) Labeling – Notwithstanding clauses (iii) and (iv) of section 355(j)(5)(F) of this title, the Secretary may require that the labeling of a drug approved under section 355(j) of this title that omits a pediatric indication or other aspect of labeling as described in paragraph (1) include—
(A) a statement that, because of marketing exclusivity for a manufacturer—
(i) the drug is not labeled for pediatric use; or
(ii) in the case of a drug for which there is an additional pediatric use not referred to in paragraph (1), the drug is not labeled for the pediatric use under paragraph (1); and
(B) a statement of any appropriate pediatric contraindications, warnings, or precautions that the Secretary considers necessary.
Otsuka argued that the language above “does not allow the omission of pediatric information protected by orphan drug exclusivity.” This is based on Otsaka’s interpretation that the BPCA only pertains to pediatric labeling information protected by a patent or a 3-year exclusivity under Section 355(j)(5)(F) of the FD&C Act, i.e., the BPCA omits Section 527 of the FD&C Act that pertains to orphan drugs. Consequently, Otsuka argued that no generic entrant, even for an indication outside of the narrow indication of the treatment of pediatric patients with Tourette’s Disorder could be approved, because such an approval would require pediatric labeling under Section 505A(o) of the BPCA, which is otherwise impermissible under the seven-year marketing exclusivity provided under the ODA. Although Abilify® is covered by several patents, generic companies anticipated that FDA would begin to approve generic versions of Abilify® after April 20, 2015. Therefore, Otsuka aimed to thwart generic entry for all indications through its orphan drug exclusivity for Tourette’s Disorder for the narrower indication for pediatric patients.
After receiving this communication from Otsuka, Otsuka alleged that FDA subsequently revised its approval of the sNDA. On February 24, 2015, the FDA sent a letter to Otsuka indicating that the FDA’s prior approval letter “contained an error in the ‘indications’ section,” and it corrected the “error.” The correction broadened the approval of Abilify® from the narrower indication of the treatment of pediatric patients with Tourette’s Disorder to the broader indication of “patients with Tourette’s Disorder.”
After Otsuka filed its complaint, FDA sent Otsuka a letter on April 10, 2015, rescinding the broader approval and adopting the narrower indication of the treatment of pediatric patients with Tourette’s Disorder. Consequently, Otsuka filed the Motion to Stay the Proceedings referenced earlier.
While this is not the first time that FDA has granted a broader indication than asked for by the sponsor of an application, it would have been be interesting to see how FDA would have responded to these allegations considering it granted an orphan drug designation to Auspex Pharmaceuticals, Inc.’s investigational compound SD-809 for the treatment of Tourette’s syndrome in the pediatric population on January 14, 2015. Nevertheless, this case will greatly impact all of the generic manufacturers that are awaiting approval after April 20, if the Court grants injunctive relief. However, more broadly, this case could greatly impact branded drug manufactures, which have observed FDA’s attempts to restrict orphan drug exclusivity in recent years. Otsuka’s attempt is certainly creative, but it is unclear at this juncture if it will be successful. We will continue to monitor the case and will report back with any developments.
