Today, the Supreme Court granted Sandoz’s petition for certiorari and Amgen’s cross-petition for certiorari in Amgen v. Sandoz, case nos. 15-1039 and 15-1195. The two cases were consolidated, and an hour was allotted for oral argument. This case will be the Supreme Court’s first interpreting the Biologics Price Competition and Innovation Act (BPCIA).
Despite nearly universal opposition from both biosimilar makers and innovator companies, FDA has issued final guidance adopting its controversial August 2015 proposal for naming biologics. Under the guidance adopted by FDA, the nonproprietary name of a biologic will consist of the core nonproprietary name of the originator product plus a meaningless but distinguishable suffix of four lowercase letters unique to each product.
Europe’s biosimilar market continues to develop, with biosimilars in new classes approved and pending in applications before the European Medicines Agency (EMA). The EMA has approved four additional biosimilars in 2016, including three biosimilars in two new classes: a biosimilar of Amgen’s Enbrel (etanercept) and two biosimilars of Sanofi’s Clexane (enoxaparin sodium). In addition to the now 22 approved biosimilars, 16 additional biosimilar applications are under evaluation by the EMA with 12 of the 16 falling in four new product classes: biosimilars of Amgen’s Neulasta (pegfilgrastim), Genentech’s Herceptin (trastuzumab), Roche’s MabThera (rituximab) and AbbVie’s Humira (adalimumab). While Europe’s biosimilar pathway offers important lessons for the U.S., the Food and Drug Administration (FDA) is setting its own path. Two of the four biosimilars approved in the U.S., Sandoz’s biosimilar of Amgen’s Enbrel and Amgen’s biosimilar of AbbVie’s Humira, were approved in the U.S. without any prior approval in Europe. The FDA has also rejected applications for proposed biosimilars with authorization and marketing experience in Europe, making clear that approval in Europe will not necessarily result in approval in the U.S.
This week’s election of Donald Trump as the next President of the United States undoubtedly impacts many sectors of the American economy, and the bio/pharmaceutical industry is no exception. Two of Trump’s stated policies might bear directly on how biologics will be protected and litigated in this country and abroad: the repeal of the Affordable Care Act of 2010 (ACA), also known as Obamacare, and the repudiation of the Trans-Pacific Partnership (TPP).
FDA Says BPCIA Poses No Fifth Amendment Taking for Innovator Biologics Submitted Prior to Its Enactment
On the same day that FDA approved the first biosimilar of Humira, the fourth biosimilar to be approved in the U.S., it also denied a citizen petition filed by Abbott Laboratories (now AbbVie) requesting that FDA not accept any filing or approve any application for a biosimilar version of Humira® (adalimumab), AbbVie’s best-selling biologic, or any other product for which a biologics license application (BLA) was submitted to FDA prior to March 23, 2010, the date on which the Biologics Price Competition and Innovation Act (BPCIA) was signed into law. AbbVie argued that to accept or approve any such biosimilar filing would constitute an unconstitutional taking under the Fifth Amendment. AbbVie filed its petition in April 2012, long before any biosimilar was approved in the U.S. and before Amgen filed its biosimilar application for Humira with FDA. All four of the U.S. biosimilars approved to date have relied on BLAs submitted to FDA prior to March 23, 2010.
The FDA on Friday approved the first U.S. biosimilar of Humira (adalimumab), AbbVie’s best-selling biologic for treatment of inflammatory conditions. The biosimilar, Amgen’s Amjevita (adalimumab-atto), received approval for all of the indications requested by Amgen: in adults, moderately to severely active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderately to severely active Crohn’s disease, moderately to severely active ulcerative colitis, and moderate to severe plaque psoriasis, and in patients four years of age and older, moderately to severely active polyarticular juvenile idiopathic arthritis. Amjevita is the fourth FDA-approved biosimilar in the U.S. As noted by the FDA, Amjevita has been approved as a biosimilar of Humira, not an interchangeable product. Amgen also submitted its Humira biosimilar for review by the European Medicines Agency in December 2015, but the EMA has yet to issue a decision.
Among the first generation of biosimilar litigation under the Biologics Price Competition and Innovation Act (BPCIA) is a dispute between Amgen and Apotex over Apotex’s proposed biosimilar versions of Amgen’s Neupogen (filgrastim) and Neulasta (pegfilgrastim). That dispute has resulted in the first final judgment in a BPCIA lawsuit. Earlier this month, Judge James Cohn of the Southern District of Florida ruled after a consolidated bench trial addressing both products that Apotex’s biosimilar applications did not infringe Amgen’s sole remaining patent, U.S. Patent No. 8,952,138 (the ‘138 patent). Meanwhile, Apotex, which remains subject to an injunction prohibiting it from marketing its biosimilar products for 180 days after they are approved, has filed a petition for a writ of certiorari to the United States Supreme Court challenging that injunction.
Amgen’s Federal Circuit Appeal: the Importance of Manufacturing Information to Biosimilar Litigation
Amgen has filed its appeal brief in Amgen v. Hospira, following the Federal Circuit’s denial of Hospira’s motion to dismiss the appeal for lack of jurisdiction. The appeal presents an important question for biosimilar litigation: where biosimilar applicants fail to provide manufacturing information in the pre-litigation information exchanges of the Biologics Price Competition and Innovation Act (BPCIA), are they required to provide that information in litigation even if it is irrelevant to the asserted patents? The question is particularly important because if the answer is no as the district court held, then innovator companies will be forced to assert manufacturing patents that they do not know to be infringed in order to be able to obtain discovery to evaluate their infringement. Amgen also addresses whether the Federal Circuit has jurisdiction to hear the appeal under either the collateral order doctrine or the All Writs Act.
The Federal Circuit has now issued two decisions interpreting the Biologics Price Competition and Innovation Act of 2009 (BPCIA). In Amgen v. Sandoz, the first decision to interpret the BPCIA, the majority held that biosimilar makers could opt out of the first step of the BPCIA’s pre-litigation disclosures, the provision requiring biosimilar makers to provide the innovator company with their abbreviated Biologics License Application (aBLA) and other manufacturing information describing the processes used to make the proposed biosimilar. The court held that the innovator company could sue under the BPCIA in such circumstances and obtain the needed information in discovery. In its second decision, Amgen v. Apotex, the court further buttressed its reasoning as to why the first step of the BPCIA’s pre-litigation provisions was optional. Amgen now appeals a discovery ruling in its biosimilar litigation with Hospira holding that Amgen v. Sandoz does not require Hospira to produce manufacturing information for its proposed biosimilar of Amgen’s Epogen (epoetin alfa). Hospira moved to dismiss the appeal as premature. The Federal Circuit denied the motion and is allowing the appeal to proceed on the merits while at the same time requiring the parties to further address jurisdictional issues.
Six years after the biosimilar pathway was enacted into law, FDA has approved three biosimilars for marketing in the US. Sandoz’s Zarxio, a biosimilar of Amgen’s Neupogen, was the first biosimilar to be approved. Zarxio, a relatively simple biologic, was approved in March 2015 under the Biologics Price Competition and Innovation Act of 2009 (BPCIA). This year, FDA approved two complex biologics, Celltrion and Pfizer’s Inflectra, a biosimilar of Janssen’s Remicade, and Sandoz’s Erelzi, a biosimilar of Amgen’s Enbrel. FDA staff and its arthritis advisory committee also recommended approval of Amgen’s proposed biosimilar of AbbVie’s Humira. On the other hand, Sandoz revealed in July that its biosimilar application for Amgen’s Neulasta, a long-acting version of Neupogen, had been rejected by FDA and Hospira did the same last year for its biosimilar application for Amgen’s EPO. Although the approvals (and rejections) provide significant insights as to FDA’s requirements, there are no simple lessons to be drawn.
On August 30 FDA approved Sandoz Inc.’s biosimilar of Enbrel (etanercept), Amgen Inc.’s blockbuster biologic for treatment of moderate to severe rheumatoid arthritis and a number of other autoimmune conditions. The biosimilar, Erelzi (etanercept-szzs), is the third biosimilar approved for marketing in the US under the Biologics Price Competition and Innovation Act of 2009 (BPCIA). Erelzi has been approved for all of Enbrel’s indications and is the first U.S. biosimilar of etanercept.
In July, the Federal Circuit decided Amgen v. Apotex, No. 2016-1308 (Fed, Cir. July 5, 2016), its second decision interpreting the U.S. biosimilar statute, the Biologics Price Competition and Innovation of Act of 2009 (BPCIA). The Federal Circuit affirmed the district court’s preliminary injunction barring Apotex from selling its proposed biosimilar until 180 days after post-licensure notice of first commercial marketing. The Federal Circuit held that 180 days’ notice was mandatory regardless of whether the biosimilar maker provided its regulatory application to the innovator as prescribed at the outset of the BPCIA procedures or not. The decision has impacted other district court litigation, including the Janssen v. Celltrion/Hospira and Amgen v. Hospira cases, since the biosimilar makers in those cases also argued that they did not need to provide 180 days’ notice of commercial marketing after being licensed by FDA.
Amgen and Hospira have fired off a dueling letters to the court in their litigation over Amgen's Epogen biosimilar, debating whether the U.S. biosimilar statute, the Biologics Price Competition and Innovation Act of 2009 (BPCIA), contains a private right of action. The letters come in the wake of the Federal Circuit’s Amgen v. Apotex decision, which held that the BPCIA’s 180-day notice of commercial marketing provision is mandatory and enforceable by an injunction.
Federal Circuit Decides Amgen v. Apotex, Holds that 180-Day Notice of Commercial Marketing is Always Mandatory in Biosimilar Litigation
Today, the Federal Circuit decided Amgen v. Apotex, No. 2016-1308 (Fed. Cir. July 5, 2016), its second decision interpreting the U.S. biosimilar statute, the Biologics Price Competition and Innovation of Act of 2009 (BPCIA). The Federal Circuit affirmed the district court’s preliminary injunction barring Apotex from selling its proposed biosimilar on the U.S. market during the 180-day post-approval notice of commercial marketing period. Writing for a unanimous panel that also included Judges Wallach and Bryson, Judge Taranto held that “the commercial marketing provision is mandatory and enforceable by injunction even for an applicant in Apotex’s position.”
Prominent among the first generation of U.S. biosimilar litigations under the Biologics Price Competition and Innovation Act (“BPCIA”) are the disputes between Amgen and Sandoz concerning Amgen’s related cancer drugs Neupogen (filgrastim) and Neulasta (pegfilgrastim).
In a consolidated litigation in the Southern District of Florida involving Apotex’s proposed biosimilars of Amgen’s Neupogen, an anti-infection drug for cancer patients, and of Amgen’s Neulasta, a long-acting version of Neupogen, Apotex participated in the pre-suit information exchanges of the BPCIA, agreed with Amgen as to what patents should be asserted in the BPCIA’s immediate litigation phase but then counterclaimed that Amgen engaged in sham litigation by bringing suit on one of the agreed patents. With trial to begin in July, Apotex recently stipulated to dismissal of its sham litigation counterclaims, leaving for another case the question of whether a biosimilar maker can both agree as to which patents to litigate in the immediate litigation phase and sustain a claim of sham litigation against the innovator for asserting agreed patents.
Amgen Appeals Ruling on Requirement to Produce Manufacturing Information for a Biosimilar Product under Amgen v. Sandoz
Amgen has appealed a partial denial of its motion to compel in Amgen v. Hospira, which sought discovery of the formulation for the cell culture media that Hospira uses to manufacture its proposed biosimilar of Amgen’s Epogen. Judge Andrews of the District of Delaware granted Amgen’s motion to the extent it sought information relevant to infringement of an asserted patent, but did not agree with Amgen’s broader argument that disclosure of manufacturing information was required under the Federal Circuit’s decision in Amgen v. Sandoz, which held that an innovator company can commence suit when a biosimilar maker fails to provide required information under the statutory process set forth in the Biologics Price Competition and Innovation Act of 2009 (BPCIA) and “access the required information through discovery.” Amgen’s discovery dispute with Hospira represents an important lesson in the aftermath of Amgen v. Sandoz. Innovator companies that assert only a subset of their manufacturing patents, as Amgen did, may only be able to obtain discovery relevant to those patents. As a result, innovator companies may choose to assert all of their manufacturing patents in order to obtain manufacturing information that biosimilar makers fail to provide under the BPCIA.
Today, the Supreme Court deferred a decision on certiorari in Amgen v. Sandoz, inviting the Solicitor General to file a brief expressing the views of the United States. Sandoz petitioned for review of one aspect of the Federal Circuit’s 2015 decision, that court’s first and so far only interpretation of the Biologics Price Competition and Innovation Act of 2009 (BPCIA), and Amgen filed a conditional cross-petition asking for review of another aspect of the decision if Sandoz’s petition were granted. The Supreme Court’s order asks the Solicitor General to comment on both petitions.
Last year, FDA published a draft guidance recommending that the nonproprietary names of biologics, including biosimilars, should consist of “core names” along with unique suffixes that are “devoid of meaning.” In a recent notice in the Federal Register, FDA stated that it will allow biologics sponsors to submit ten suggested suffixes for their products under FDA’s proposed naming scheme. This new recommendation represents a change from last year’s guidance, which invited sponsors to submit three suggested suffixes.
A 70-group coalition of healthcare stakeholders urged the FDA to incorporate meaningful and therefore memorable suffixes into its distinguishable naming system for biological medicines to provide strong patient protections and provider confidence. The coalition emphasized that “meaningful suffixes are easier for patients, providers and pharmacists to both recognize and remember, thus facilitating accurate association between adverse effects and specific products.” The coalition explained that meaningful suffixes based on the name of the manufacturer, such as the “sndz” suffix used for the first approved biosimilar, Sandoz’s Zarxio (filgrastim-sndz), instead of the random suffixes proposed in FDA’s most recent draft guidance and used for the first time in FDA’s recent approval of a second biosimilar, Celltrion and Pfizer’s Inflectra (infliximab-dyyb), would promote manufacturer accountability. Notably, FDA used a random suffix for the nonproprietary name of Inflectra despite widespread criticism by innovators and biosimilar makers alike of FDA’s naming approach.
On April 5, the FDA announced the approval of Inflectra, Celltrion and Pfizer’s biosimilar of Johnson & Johnson’s Remicade (infliximab). Inflectra is now the second biosimilar approved for sale in the United States, after Sandoz’s Zarxio. Inflectra’s label and naming reflect the latest FDA guidance.
Amgen’s Enbrel (etanercept), a blockbuster biologic treatment for a number of autoimmune diseases, including rheumatoid arthritis and psoriasis, has been an attractive target for biosimilar makers. Sandoz, the maker of Zarxio (filgrastim-sndz), the only biosimilar launched in the US to date, is also first in line with an Enbrel biosimilar in the US. Last October, Sandoz announced that FDA accepted its regulatory application for a proposed Enbrel biosimilar for review. Sandoz is seeking marketing approval for all of Enbrel’s medical indications. But Sandoz’s proposed Enbrel biosimilar brought litigation under the US biosimilars statute, the Biologics Price Competition and Innovation Act of 2009 (BPCIA).
On Thursday, FDA released draft guidance clarifying its position on labeling biosimilar products. While the guidance addresses some of the concerns raised by physicians and innovator companies, FDA’s guidance largely continues to treat biosimilars like generics for purposes of labeling.
Amgen has fired back in response to Sandoz’s cert petition in Amgen v. Sandoz, arguing that the Supreme Court should not hear the case—but that if it does, it should also review the Federal Circuit’s holding on the Biologics Price Competition and Innovation Act’s (BPCIA’s) “patent dance.” Though Amgen declined to seek cert on the patent dance issue, which it lost at the Federal Circuit, it has now filed a conditional cross-petition on that issue along with its opposition to Sandoz’s petition for review of the Federal Circuit’s holding on the BPCIA’s notice of commercial marketing.
Despite mixed results, biosimilar makers continue to turn to inter partes review (IPR) proceedings in order to challenge innovator patents protecting some of the most important biologics.
In the latest skirmish between Amgen and Sandoz under the U.S. biosimilars statute, the Biologics Price Competition and Innovation Act of 2009 (BPCIA), Amgen has filed a new declaratory judgment claim alleging violations of the BPCIA. As described in Amgen’s March 4 complaint, after filing an application for a biosimilar version of Amgen’s cancer drug Neulasta, Sandoz cut short the BPCIA patent dance and demanded that Amgen file an immediate patent infringement suit, claiming that Amgen would otherwise lose its rights to seek lost profits and injunctive relief. Amgen responded with a suit for a declaration that it had no obligation to go forward with the immediate litigation phase of the BPCIA after Sandoz cut off the pre-suit procedures.
Sandoz has filed a petition for a writ of certiorari in Amgen v. Sandoz, the first and, to date, only Federal Circuit decision interpreting the Biologics Price Competition and Innovation Act (BPCIA). Sandoz is challenging the Federal Circuit's ruling that biosimilar applicants must observe a 180-day notice period after their products are approved by the FDA.
AbbVie, Inc., a biopharmaceutical company, has submitted a citizen petition to the FDA regarding determinations of interchangeability under the BPCIA. An interchangeable biological product is biosimilar to a reference product and meets additional, heightened standards for interchangeability. While biosimilars are required to be highly similar to an FDA-approved reference product, an interchangeable biological product is expected to produce the same clinical result as the reference product in any given patient. A determination of interchangeability is significant because an interchangeable biological product may be substituted for a reference product by a pharmacist without requiring permission from the physician who prescribed the reference product. While the FDA approved the first biosimilar biological product in early 2015, it has yet to issue a decision that one biological product is “interchangeable” with another.
In 2015, FDA issued a number of final guidance documents for biosimilars but many fundamental questions remain unsettled, including the requirements for labeling of biosimilars, interchangeability, and naming. There is much ahead for the US biosimilars pathway in 2016.
2015 was a landmark year for biosimilars. It began with the approval of the first US biosimilar, Sandoz’s Zarxio, in March 2015 under the biosimilars pathway. Zarxio entered the US market in September. Many expected the floodgates to open after Zarxio’s approval but Zarxio remains the only approved US biosimilar to this day, although that is expected to change this year. Seven other biosimilar applications were filed in 2014/2015 and are either being reviewed by FDA or have to be refiled. Most of these applications are to complex biologics. 2016 should provide significant insights into how FDA determines biosimilarity and extrapolation for these complex products.
On January 26, 2016, the World Health Organization (WHO) unveiled the final version of its proposal for a worldwide biosimilar naming convention. The WHO proposes to add a “biologic qualifier” (BQ), which consists of four random consonants and an optional two-digit checksum, as an identifier that follows the nonproprietary name of each biologic and biosimilar product. This proposal resembles FDA’s biosimilar naming proposal, which adds four random consonants as a suffix to nonproprietary names. Industry and healthcare stakeholders have criticized FDA’s proposal to use random suffixes, instead of meaningful—and therefore memorable—ones, due to a greater likelihood of reporting and prescription errors with meaningless names. The WHO proposal, which uses a randomly generated separate identifier, is likely to draw similar criticism.
Nearly six years after the U.S. biosimilar statute was passed, the number of reported decisions addressing the statute can still be counted on the fingers of two hands, but this has been enough for some clear patterns to emerge. Again and again, biosimilar applicants and innovators have taken consistent, but diametrically opposed, positions on fundamental issues concerning the operation of the statute. As the courts have resolved these disputes, the basic framework for biosimilar patent litigation has taken shape – at least until the next generation of biosimilar applications raises new issues.
Amgen has decided not to seek Supreme Court review of the Federal Circuit’s Amgen v. Sandoz decision, as the January 14, 2016 deadline to file has now passed without Amgen petitioning for certiorari. In Amgen, the Federal Circuit held that the BPCIA’s “patent dance” patent dispute resolution procedures are essentially optional. With the Federal Circuit having already denied en banc review, Amgen’s decision not to seek cert appears to mean that the patent dance is now optional as a matter of settled law. There is, however, one caveat: if Sandoz seeks cert and the Court accepts, Amgen could file a cross-motion on the patent dance issue.
The Federal Circuit Will Hear Apotex’s Appeal from a Preliminary Injunction Under the BPCIA in Early 2016
In early 2016, the Federal Circuit will hear Apotex’s appeal from a preliminary injunction barring Apotex from selling its proposed Neulasta biosimilar for 180 days after FDA approval. Briefing will be complete on February 12, 2016, and the Federal Circuit agreed to place the case on the oral argument calendar soon thereafter. Apotex had asked for a more expedited schedule but was not able to provide any specific evidence of when its proposed biosimilar product will be approved.
On December 9, a federal district court in Florida issued a preliminary injunction prohibiting Apotex from selling a proposed biosimilar version of Amgen’s cancer drug Neulasta for 180 days after the biosimilar is approved. In the decision, the district court resolved in Amgen’s favor a dispute over the meaning of the Federal Circuit’s recent decision in Amgen v. Sandoz, the first and to date the only appellate decision addressing the Biologics Price Competition and Innovation Act of 2009 (BPCIA).
This fall marks the tenth anniversary of the effective date of the European Medicines Agency's Guideline on Similar Biological Medicinal Products. Over the past ten years, the EMA has approved 19 biosimilars corresponding to 6 different reference drugs, under the Guideline, and a biosimilar of a seventh is nearing final approval. Since the EU system served as the model, in many respects, for the biosimilar approval process in the U.S. and other developed countries, the European experience sheds light on what we can expect in the development and commercializations of biosimilars in the U.S. in the next several years.
On November 19, 2015, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) gave a positive opinion, recommending marketing authorization of Samsung Bioepis’s Benepali, the first biosimilar of Enbrel (etanercept), in Europe. Enbrel is a blockbuster treatment for rheumatoid arthritis and a number of other autoimmune conditions associated with elevated levels of tumor necrosis factor alpha (TNF-alpha), a protein that plays an important role in promoting inflammation. The CHMP recommended approval of Benepali for these conditions. In the US, FDA recently accepted Sandoz’s regulatory application for its proposed biosimilar of Enbrel for review. Sandoz is seeking approval for all of Enbrel’s indications. FDA’s review of Sandoz’s proposed biosimilar will provide important information on the requirements for biosimilarity and extrapolation for complex biologic products.
FDA has received comments from more than 170 groups on its proposal for naming biosimilars. Biosimilar makers, insurers and pharmacies largely oppose distinct nonproprietary names (also known as proper names) for biosimilars. By contrast, innovators (including those that develop biosimilars), healthcare providers and patient advocacy groups view them as critical to ensuring patient safety. However, most stakeholders in both camps urged FDA to use meaningful suffixes to distinguish biosimilars from originator products rather than suffixes “devoid of meaning.” FDA proposed to add meaningless suffixes to the nonproprietary names of originator products to address concerns of biosimilar makers that distinct names would discourage adoption of biosimilar products. But biosimilar makers expressed concern that such meaningless suffixes will lead to a variety of errors and ultimately endanger public safety. FDA may now revisit its proposal given the largely uniform preference of innovators and biosimilar makers alike for meaningful and memorable nonproprietary names, such as those that identify the manufacturer of the biologic.
In its draft guidance, FDA proposed distinguishable nonproprietary names for biosimilars to promote the safety of patients receiving biologic medicines and minimize inadvertent substitution of biologics that have not been determined to be interchangeable. FDA did not make a proposal for naming interchangeable biological products. Instead, FDA requested comments on how to name such products in addition to seeking comments on its approach to naming biosimilars. Stakeholders’ comments are now in. Innovator companies (including those that also develop biosimilars), healthcare providers and patient advocacy groups favor distinguishable nonproprietary names for biosimilars. Biosimilar makers, insurers, pharmacies, and the FTC, by contrast, largely fall into a different camp; they argue that distinct names are unnecessary for monitoring biosimilars and will likely bias providers against prescribing them. Notably, the two camps came together on the naming of interchangeable products. Since interchangeable products will likely first be approved as biosimilars, both camps advocated keeping the initial biosimilar name rather than changing it after approval as an interchangeable product. As a result of this unified view, FDA is likely to expand the naming approach it ultimately adopts for biosimilars to interchangeable products.
Last month, in a case under the Biologics Price Competition and Innovation Act of 2009 (BPCIA) involving Apotex’s proposed biosimilar of Amgen’s Neulasta (pegfilgrastim), Apotex accused Amgen of sham litigation for bringing a patent infringement claim on a that the parties agreed to litigate during the immediate litigation phase of the BPCIA. In its Answer to Apotex’s Counterclaims, Amgen pointed out that Apotex had agreed to include the patent in the BPCIA infringement action, despite having a statutory option to disagree.
After the FDA approved the first U.S. biosimilar, Sandoz’s Zarxio (filgrastim-sndz), earlier this year, many predicted that the floodgates would open for biosimilar products. That has not been the case. No other U.S. biosimilar product has been approved. And, as FDA’s recent rejection of Hospira’s EPO biosimilar application suggests, Zarxio’s approval may ultimately provide little guidance for more complex products.
At long last, the final text of the Trans-Pacific Partnership, a free trade agreement among a dozen Pacific Rim nations, has now been made available to the public. The chapter on intellectual property, however, does not appear to have any material changes relating to exclusivity for new biologics from the leaked draft released by WikiLeaks last month. Just as the provisions in the leaked draft did, Articles 18.50 and 18.52 give countries a choice between, on the one hand, at least eight years of exclusivity or, on the other hand, at least five years of exclusivity plus unspecified “other measures” and protection through “market circumstances.” Additionally, the agreement seems to provide for only market exclusivity, not data exclusivity. The TPP bars biosimilar applicants from entering the market during the exclusivity period, but does not appear to prevent them from accessing innovators’ regulatory data.
The first biosimilar makers to file regulatory applications with FDA attempted to bypass all or a subset of the patent litigation provisions of the Biologics Price Competition and Innovation Act of 2009 (BPCIA). Apotex, the third biosimilar maker to file an application for approval of a biosimilar product with FDA, chose a different course. Apotex participated in and completed the BPCIA’s pre-suit information exchanges (also known as the “patent dance”) for its proposed biosimilar of Amgen’s Neulasta (pegfilgrastim). As Amgen’s recent lawsuit shows, Apotex followed the patent dance again for its proposed biosimilar of Amgen’s Neupogen (filgrastim).
After half a decade of negotiations, the Trans-Pacific Partnership seems to do little more than maintain the status quo for biologics. A leaked draft of the agreement appears to require member states to provide between five and eight years of exclusivity for new biologics. But almost all TPP signatories provide that duration under current law, and some governments have already said that the pact will not require them to change their laws. The United States will be able to maintain its current twelve years of protection. Additionally, the agreement appears to provide only market exclusivity, which prevents biosimilars from being sold, and not data exclusivity, which prevents biosimilar makers from using innovators’ regulatory data. Because the TPP largely reflects existing exclusivity periods for biologics, many view it as a missed opportunity for incentivizing global investment in new biologics.
This morning, the full Federal Circuit declined to rehear en banc Amgen v. Sandoz, the first appellate decision interpreting the Biologics Price Competition and Innovation Act of 2009 (BPCIA). The decision to deny en banc review comes as something of a surprise, as the panel decision was fractured, and neither party disputed that it raised important issues of first impression. Indeed, both parties sought en banc review, albeit on different issues. In a per curiam order issued this morning, the court denied both petitions. Unless the Supreme Court (or a later en banc court) intervenes, the panel’s decision will stand as the Federal Circuit’s authoritative statement on the issues presented.
Last month, Amgen sued Hospira in Delaware under the Biologics Price Competition and Innovation Act of 2009 (BPCIA) over Hospira’s proposed biosimilar version of Amgen’s Epogen (epoetin alfa). Amgen brought, among others, two BPCIA-specific claims under 42 U.S.C. § 262(l)(2)(A) (relating to Hospira’s alleged failure to provide the required manufacturing information) and 42 U.S.C. § 262(l)(8)(A) (relating to Hospira’s allegedly ineffective 180-day notice of commercial marketing). On October 13, Hospira moved to dismiss these claims, arguing that Congress did not create a private right of action to enforce the BPCIA. The issues raised in Hospira’s motion to dismiss are currently before the Federal Circuit in Amgen’s and Sandoz’s petitions for rehearing en banc.
A final agreement has been reached on the Trans-Pacific Partnership that could provide for as little as five years of exclusivity for biologics. The final text of the agreement is not yet officially available and its exact contours are unclear, but reports indicate that it includes a complicated compromise providing for between five and eight years of exclusivity. This represents a setback for the United States, which sought twelve years of exclusivity throughout the negotiations. Industry groups have also expressed disappointment.
Amgen recently sued Apotex under the Biologics Price Competition and Innovation Act of 2009 (BPCIA) over Apotex’s proposed biosimilar of Amgen’s Neulasta (pegfilgrastim), a long-lasting version of Neupogen. This is the first BPCIA suit to reach the courts after completion of the BPCIA’s pre-suit information exchange, the so-called patent dance. On October 5, 2015, Apotex filed its Answer with Counterclaims. Despite agreeing on which patents should be the subject of immediate patent infringement litigation under the BPCIA, Apotex now alleges that Amgen’s suit on one of those patents is sham litigation in violation of the Sherman Act.
Sandoz Inc. announced on October 2, 2015 that FDA accepted its regulatory application for a proposed biosimilar of Amgen Inc.’s biologic arthritis drug Enbrel for review. The acceptance comes years after Sandoz attempted to bypass the litigation provisions of the Biologics Price Competition and Innovation Act of 2009 (BPCIA). It remains to be seen whether Sandoz now will follow the BPCIA and provide its regulatory application and other manufacturing information to Amgen since the Federal Circuit has recently held that doing so is optional in Amgen v. Sandoz, another case involving the same parties and the Federal Circuit’s first decision to interpret the BPCIA. Amgen is currently seeking en banc review of this ruling.
The FDA approved label for the first U.S. biosimilar, Sandoz’s Zarxio, has raised concerns. Zarxio was launched on September 3, 2015 with a label that does not state that the product was approved as a biosimilar to Amgen’s Neupogen and that it has not been determined to be interchangeable to Neupogen. Instead, Zarxio’s label is nearly identical to that of Amgen’s Neupogen and does not identify the information provided by Sandoz to FDA to obtain Zarxio’s approval, including information on immunogenicity specific to Zarxio. AbbVie has supplemented its citizen petition urging FDA not to allow biosimilars to be labeled like generic drugs since biosimilars, unlike generic drugs, are not identical to the originator product and requesting distinct labeling for biosimilars. In briefing U.S. senators on September 17, FDA promised to issue guidance on labeling of biosimilars.
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