Spectrum Pharms., Inc. v. Burwell

Case Name: Spectrum Pharms., Inc. v. Burwell, No. 15-5166, 2016 U.S. App. LEXIS 10095 (D.C. Cir. June 3, 2016) (Circuit Judges Griffith, Cavanaugh, and Wilkins presiding; Opinion by Griffith) (Appeal from D.D.C., Lamberth, J.) 

Drug Product and Patent(s)-in-Suit: Fusilev® (levoleucovorin); N/A

Nature of the Case and Issue(s) Presented: Spectrum markets Fusilev for two indications: (i) treating side effects of the cancer medicine methotrexate (“the methotrexate indication”); and (ii) treating pain associated with colorectal cancer (“the colorectal indication”). Spectrum had exclusivity under the Orphan Drug Act for the methotrexate indication until 2015, and has exclusivity for the colorectal indication until 2018.

Sandoz received ANDA approval for generic Fusilev, indicated for the methotrexate indication, pursuant to 21 C.F.R. § 314.94(a)(8)(iv) carving out the colorectal indication.

Spectrum challenged the FDA’s approval of Sandoz’s ANDA, arguing primarily that the FDA was willfully blind to the fact that the generic would be used for the colorectal indication. As we reported in 2015, the district court rejected Spectrum’s arguments in the context of summary judgment. Spectrum appealed, and the DC Circuit affirmed.

Why Sandoz prevailed: Spectrum’s primary argument concerned the FDA’s interpretation of the Orphan Drug Act’s requirement that once the FDA approves a pioneer drug “designated…for a rare disease or condition,” for seven years it may not approve a generic application “for such drug for such disease or condition.” The FDA interprets “for such disease or condition” to refer solely to the uses included on a drug’s label, while Spectrum argued that the term also encompass a producer’s intention for off-label use.

The DC Circuit, giving Chevron deference to the FDA’s interpretation, considered whether it was a permissible construction. The Circuit found two reasons to find the construction permissible. First, it found the interpretation “closely hews” to the statutory language. This is because the statute is “disease-specific” and not “drug-specific.” Further, the statutory language is directed to drug applications, which necessarily entail stated indications but not intended off-label uses. Second, the Circuit found the FDA’s interpretation to represent a reasonable weighing of the Orphan Drug Act’s balancing of both promoting innovation and making drugs affordable.

Spectrum also argued that, even if the Orphan Drug Act does not bar the FDA’s action, then 21 C.F.R. § 316.3(b)(12) does.  That regulation bars the FDA from approving a generic that is “intended” for the same use as the pioneer during the exclusivity period.  The word “intended,” according to Spectrum, requires the FDA to consider how Sandoz subjectively intended doctors and patients to use its drug. The Circuit, however, said that the agency can properly determine a drug’s purpose by looking solely to the labeled uses proposed in the application. Should Sandoz later improperly promote off-label use, the court said, Spectrum could pursue an enforcement action.

Spectrum further argued that the FDA’s approval of large packaged doses of the generic Fusilev represented an unjustified change in the FDA’s position, as the FDA had purportedly found these doses inappropriate for the methotrexate indication. The Circuit Court, however, concluded that the FDA had previously determined that the large packaged doses were appropriate for the methotrexate indication. As evidence for this conclusion, the Circuit noted that Spectrum itself had applied for, and received, approval for large packaged doses. Further buttressing the conclusion, the FDA had considered the appropriateness of large packaged doses when Spectrum filed a Citizen’s Petition requesting the FDA not approve Sandoz’s large package doses.

Finally, Spectrum argued that the FDA, which had expedited Sandoz’ ANDA in response to a drug shortage, was required to give Spectrum notice of the application and an opportunity to be heard, pursuant to 21 U.S.C. § 360cc(b)(1). More specifically, Spectrum argued that the Orphan Drug Act creates a notice obligation even in situations where the FDA does not cut short a market-exclusivity period. The court rejected that argument, stating that the clear purpose of the notice obligation is to protect the rights of producers of pioneer drugs in the event the FDA decides a drug shortage requires it to eliminate those rights. In contrast, the statute says nothing at all about notice requirements when the FDA expedites its review of an ANDA or simply evaluates a drug shortage without more.