In the first skirmishes between biosimilar makers and innovator companies, biosimilar makers attempted to bypass the litigation provisions of the Biologics Price Competition and Innovation Act of 2009 (BPCIA) through the filing of declaratory judgment actions, or by not participating in all or a subset of the BPCIA’s pre-suit information exchanges (also known as the “patent dance”). Apotex, the third biosimilar maker to file an application for approval of a biosimilar product with FDA, chose a different path. As Amgen’s recent lawsuit against Apotex reveals, Apotex is the first biosimilar applicant to participate in and complete the carefully orchestrated pre-suit information exchanges of the BPCIA.
Last year, Apotex submitted an application for a biosimilar version of Amgen’s Neulasta (pegfilgrastim), a blockbuster drug used to prevent infections in cancer patients. Amgen’s Neulasta is an improved long-lasting version of Amgen’s Neupogen that was approved by FDA in 2002. Neulasta consists of Neupogen with a covalently bound polyethylene glycol (PEG) molecule that allows Neulasta to be administered less frequently than Neupogen.
After the FDA accepted Apotex’s biosimilar application for review in December 2014, Apotex proceeded to follow the information exchange provisions of the BPCIA. As described in Amgen’s complaint, Apotex provided Amgen a copy of its abbreviated Biologics License Application (aBLA) within twenty days of its aBLA being accepted for review. 42 U.S.C. § 262(l)(2)(A). On February 27, 2015, within 60 days of receiving the aBLA, Amgen provided its list of patents that could be asserted against Apotex. 42 U.S.C. § 262(l)(3)(A). On April 17, 2015, within 60 days of receiving Amgen’s list of patents, Apotex provided Amgen with its invalidity and noninfringement contentions. 42 U.S.C. § 262(l)(3)(B). (On the same day, Apotex also provided a 180-day notice of commercial marketing although its biosimilar version of Neulasta had not yet been approved.) On June 16, 2015, within 60 days of receiving Apotex’s contentions, Amgen provided Apotex with its contentions. 42 U.S.C. § 262(l)(3)(C). This completed the patent information exchanges of the BPCIA.
The parties then proceeded to determine which of the listed patents should be the subject of the first phase of BPCIA litigation (the so-called “immediate litigation phase”). The BPCIA does not prescribe an exact date after the completion of the patent information exchanges by which the parties need to begin negotiating the patents to be litigated immediately. But according to Amgen’s complaint, Amgen and Apotex began to negotiate on June 22, 2015, about a week after Amgen served its infringement and validity contentions. The negotiations lasted fifteen days, until July 7, as set forth in the BPCIA. 42 U.S.C. § 262(l)(4). On July 7, Amgen and Apotex agreed that two patents should be the subject of an immediate patent infringement lawsuit. 42 U.S.C. § 262(l)(6)(A). Amgen then sued Apotex on August 6 in the Southern District of Florida, within the required 30 days of the parties agreeing on the patents to be litigated immediately. 42 U.S.C. § 262(l)(6)(A).
Amgen sued Apotex on two patents, a manufacturing patent and a patent covering Neulasta itself. The patent covering Neulasta issued in October of 1998 and is about to expire. The manufacturing patent, by contrast, issued just this year. In addition to patent infringement, Amgen sued Apotex for violating the BPCIA’s notice of commercial marketing provision. According to the complaint, Apotex 1) provided its 180-day notice of commercial marketing long prior to any FDA approval, 2) has refused to provide a “legally effective Notice of Commercial pursuant to 42 U.S.C. § 262(l)(8)(A)” after approval by FDA, and 3) “intends to market its [proposed biosimilar] immediately upon receiving FDA approval.” Amgen seeks an injunction preventing Apotex from marketing its product until at least 180 days after FDA approval, i.e., the first time that Apotex can provide an effective notice of commercial marketing under the Federal Circuit’s interpretation of that provision in Amgen v. Sandoz.
Notably, Apotex’s decision to comply with the patent dance came before the decision in Amgen and the court’s interpretation of the information exchange provisions of the BPCIA as optional. Its notice of commercial marketing also preceded the decision and is legally ineffective under it. The panel’s interpretation of the information exchange and notice of commercial marketing provisions, however, may not be the last word. Both Amgen and Sandoz have sought rehearing en banc. A number of biosimilar makers are also urging the full court to review the notice of commercial marketing provision and hold that the 180-day notice of commercial marketing can be provided at any point, even before regulatory approval, and that it does not need to be provided at all. Apotex has not weighed in on these issues.
Amgen’s suit against Apotex has been set for trial in July 2016. But it is unclear when Apotex’s proposed biosimilar of Neulasta will be approved, much less reach the market. Apotex’s product is more complex than Sandoz’s Zarxio, a biosimilar of Neupogen and the only biosimilar to have been approved by FDA. While Zarxio sailed through the regulatory process and received marketing approval by FDA’s targeted 10-month decision date, Apotex’s more complex product appears to be progressing more slowly. FDA has not announced plans for an advisory committee meeting for Apotex’s product although the application was accepted for review in December 2014 and FDA’s 10-month targeted decision date for the application is this October. Advisory committee meetings are targeted to occur in the eighth month of acceptance for review, but passed last month for Apotex’s product without comment. In the meanwhile, one thing is clear; FDA’s review of Apotex’s product should provide important information on the requirements for biosimilarity for more complex biologics.