Last week, the U.S. Food and Drug Administration (“FDA”) issued a final rule to amend its regulation that defines the term “biological product” in line with the definition set by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), as amended by the Further Consolidated Appropriations Act, 2020, enacted on December 20, 2019 (“FCA Act”).
In December, in Amgen v. Hospira, 944 F.3d 1327 (Fed. Cir. 2019), a panel of the Federal Circuit issued the first decision applying the statutory Safe Harbor of 35 U.S.C. § 271(e)(1) to BPCIA patent litigation. The Federal Circuit affirmed the jury’s finding that Hospira’s pre-approval manufacture of batches of its biosimilar was an act of infringement of Amgen’s manufacturing patents not protected by the Safe Harbor, even though data from those batches was used to support Hospira’s BLA. The court held that the relevant Safe Harbor inquiry “is not how Hospira used each batch it manufactured, but whether each act of manufacture was for uses reasonably related to submitting information to the FDA.” Hospira has now petitioned for rehearing en banc, arguing that the court’s holding “calls into question the continuing viability of the Safe Harbor, particularly in the context of BPCIA litigation.”
Federal Circuit Walks Back Its “Exceptional” Stance on the Doctrine of Equivalents in the Latest Amgen v. Sandoz Decision
In Amgen’s long-running dispute with biosimilar-maker Sandoz over biosimilar versions of Amgen’s filgrastim (Neupogen®) and pegfilgrastim (Neulasta®) biologics, the Federal Circuit earlier this year affirmed summary judgment of no literal infringement and no infringement under the doctrine of equivalents. Amgen Inc. v. Sandoz Inc., 923 F.3d 1023 (Fed. Cir. May 8, 2019). In so holding, the panel stated that “the doctrine of equivalents applies only in exceptional cases.” Amgen petitioned for rehearing en banc, arguing that the Federal Circuit had overstated the law. According to Amgen’s petition, “[s]uch a rule is contrary to Supreme Court precedent and [Federal Circuit] precedent.” This week, the Federal Circuit course-corrected, granting Amgen’s petition without explanation for the limited purposes of removing the “exceptional” language from its prior decision.
On July 23, 2019, Amgen, maker of the cancer treatment drug Neupogen (filgrastim), filed patent infringement claims in the Southern District of California against Tanvex Biopharma over Tanvex’s proposed filgrastim biosimilar. See Amgen Inc. v. Tanvex BioPharma USA, Inc., 3:19-cv-01374-BEN-MSB. Amgen asserts a patent that claims methods of refolding recombinant proteins used in the manufacture of Neupogen.
Earlier this month, AbbVie filed suit against Sandoz’s proposed biosimilar to AbbVie’s HUMIRA® (adalimumab). Invoking the Biosimilar Price Competition and Innovation Act (“BPCIA”), AbbVie asserts two patents protecting Humira, a fraction of the 84 patents AbbVie wished to litigate. Taking full advantage of the pre-litigation “patent dance,” Sandoz limited the number of patents-in-suit to just two. As this case illustrates, following the patent dance affords biosimilar makers considerable control and power over the scope of biosimilar lawsuits.
On July 20, 2018, FDA approved Pfizer’s biosimilar of Amgen’s Neupogen® (filgrastim). Pfizer’s product, Nivestym™, is the second biosimilar of Neupogen to be approved after Sandoz’s Zarxio®, the first approved biosimilar in the United States. Pfizer’s Nivestym gained approval for all eligible Neupogen indications.
Amgen has sued Apotex in connection with Apotex’s efforts to market biosimilar versions of Amgen’s cancer drugs Neupogen (filgrastim) and Neulasta (pegfilgrastim). In a complaint filed on August 7 in the Southern District of Florida, Amgen alleges infringement of U.S. Patent No. 9,856,287. This is the third time that Amgen has filed a BPCIA lawsuit against Apotex in connection with its filgrastim and pegfilgrastim biosimilars.
Earlier this month, FDA issued final guidance on the labeling of biosimilar products. The final guidance continues the approach adopted in FDA’s March 2016 draft guidance. That approach largely treats biosimilars like generic drugs for purposes of labeling, even though biosimilars, unlike generic drugs, are not exact copies of innovator products.
On July 18, FDA released its long-awaited Biosimilars Action Plan (“BAP”). In prepared remarks to the Brookings Institution the same day, FDA Commissioner Scott Gottlieb described the BAP as “enabling a path to competition for biologics from biosimilars” in order to “reduc[e] costs and to facilitat[e] more innovation.” While the BAP is straightforward, the Commissioner’s remarks included unexpected jabs at innovator drug makers for what FDA believes is anticompetitive conduct. The speech was likely driven by the Trump Administration’s American Patients First plan, which sets as a top FDA priority the reduction of prescription drug prices, including by reducing “gaming” of regulatory requirements, but what the speech achieves given the role of FDA remains unclear.
Analytical studies to demonstrate that a biosimilar is highly similar to its reference product are central to the biosimilar development and approval process. For this reason, there have been calls from industry for more guidance from FDA on its expectations for evaluating and demonstrating analytical similarity.
Generics and biosimilar makers have increasingly used inter partes reviews, proceedings made possible by the America Invents Act, to challenge patents protecting innovator small-molecule drugs and biologic medicines. Senator Orrin Hatch, co-author of the Hatch-Waxman Act, has introduced an amendment that would require these manufacturers either to take advantage of the abbreviated regulatory approval pathways provided by the Hatch-Waxman Act and BPCIA and challenge innovator patents in district court or to challenge innovator patents in IPRs before the PTAB, but not both. Senator Hatch explains that while he strongly supports IPRs and the America Invents Act and that IPRs are of particular importance to the tech community to fight “patent trolls,” they are also “producing unintended consequences in the Hatch-Waxman context” and “threaten to upend the careful Hatch-Waxman balance by enabling two separate paths to attack a brand patent.” If enacted, generics and biosimilar makers that choose to take advantage of the abbreviated regulatory process will challenge innovator patents in court rather than in IPRs before the PTAB.
As biosimilar litigation between Amgen, the maker of Enbrel® (etanercept), and Sandoz, the maker of biosimilar ErelziTM (etanercept-szzs) heads toward trial before Judge Claire Cecchi in the District of New Jersey, Sandoz is seeking to stave off Amgen’s infringement claims for three of the patents in suit by pointing to its recent amendment to the Erelzi label, which “carves out” certain treatment indications listed on the Enbrel reference label and, Sandoz argues, moots any claim that Erelzi infringes Amgen’s patents covering the use of etanercept to treat those conditions.
Yesterday, Pfizer announced that FDA had approved Retacrit® (epoetin alfa-epbx), a biosimilar of Amgen’s Epogen® and Johnson & Johnson’s Procrit® (epoetin alfa). Epoetin alfa (EPO) is a blockbuster treatment for anemia. Retacrit is the first EPO biosimilar approved in the United States. EPO biosimilars have been marketed in the EU for over a decade. Hospira (now a Pfizer company) initially filed an application for approval of its EPO biosimilar in 2014. FDA rejected that application in a complete response later and Hospira later resubmitted it after addressing FDA's concerns. While Retacrit received a favorable FDA advisory committee recommendation in May 2017, it was rejected again in a second complete response letter due to concerns with the proposed manufacturing site for the biosimilar. Nearly a year later, FDA approved Retacrit. Pfizer plans to launch Retacrit this year.
Last month, Amgen sued Adello for patent infringement under the Biologics Price Competition and Innovation Act of 2009 (BPCIA) in connection with Adello’s proposed biosimilar of Amgen’s Neupogen. Adello elected to bypass the pre-suit procedures of the BPCIA and did not provide any information regarding its biosimilar or how it is manufactured to Amgen. In its lawsuit, Amgen asserts 17 patents against Adello blind. The lawsuit illustrates the consequences of the Supreme Court’s and Federal Circuit’s recent decisions holding that provisions of the BPCIA requiring production of information to the innovator company are not enforceable under federal or state law and that information needed to assess infringement can only be obtained by filing a patent infringement lawsuit.
Win or Go Home? Standing to Appeal PTAB Decisions Upholding Patentability to the Federal Circuit Before Submitting a Biosimilar Marketing Application
Biosimilar developers have been aggressive in filing petitions for inter partes reviews (IPRs) of biologics patents before the Patent Trial and Appeal Board (PTAB), many of them preceding the filing of a marketing application. Such early IPRs are attractive to biosimilar makers, because they provide a chance to challenge innovator patents years before the biosimilar maker files a marketing application with FDA. Since a petitioner need not have Article III case-or-controversy standing to bring an IPR, the remoteness and uncertainty of future infringement in such circumstances does not preclude these early IPRs. Under settled precedent, however, a biosimilar maker must have Article III standing to seek a Federal Circuit appeal if the PTAB issues a final decision upholding the challenged patent. A decision expected from the Federal Circuit this quarter in Momenta Pharmaceuticals, Inc. v. Bristol-Myers Squibb Co., No. 17-1694 (Fed. Cir. argued Dec. 5, 2017) will address how and when a biosimilar maker can establish that standing.
The Federal Circuit’s recent decision in Amgen v Sandoz provides a measure of clarity for innovator companies and biosimilar makers eyeing patent litigation. While the Supreme Court of the US held in June that initiating the pre-litigation information exchanges set out in the Biologics Price Competition and Innovation Act (BPCIA) – colloquially referred to as the “patent dance” – cannot be enforced under federal law, the Federal Circuit’s decision goes a step further. It holds that initiation of the exchanges cannot be enforced under state law, either. As a result, innovators seeking to compel disclosures from biosimilar makers have no recourse other than to sue for infringement. For a number of reasons, however, the decision might not prove as impactful in the long run as it may seem.
To continue reading Irena Royzman and Michael Fresco's article from Intellectual Property Magazine, please click here.
On December 19, 2017, FDA approved Spark Therapeutics’ gene therapy Luxturna (voretigene neparvovec-rzyl), the United States’ first gene therapy approved to treat an inherited genetic disease. This approval follows that of Novartis’ Kymriah (tisagenlecleucel) and Gilead Sciences’ Yescarta (axicabtagene ciloleucel), both gene therapies approved earlier this year to treat certain forms of cancer. Gene therapy has arrived, and although the genetic material central to these new treatments is not expressly listed in the statutory definition of “biological product,” FDA is regulating these products as biologics, giving them twelve-year non-patent exclusivity.
2017 has been a record-setting year for biosimilar approvals in Europe. Although the first biosimilars to the European market were approved in 2006 and 2007, the number of approved biosimilars has doubled in the past two years. These approvals have expanded the market into new therapeutic areas and new classes of biologics.
Marketing approval for US biosimilars has taken off in 2017. FDA has approved five biosimilar products this year, increasing the number of approved biosimilars from four to nine. In addition to new biosimilars of AbbVie’s Humira and Janssen’s Remicade, FDA has approved the first two biosimilars for the treatment of cancer. All five of the products approved this year are biosimilars of complex blockbuster therapeutic antibodies.
The Federal Circuit ruled that Amgen’s state law unfair competition claims, which were premised on Sandoz’s failure to follow the patent dance, are preempted by the BPCIA. The decision largely affirms the status quo, making clear that biosimilar applicants may opt out of the patent dance without incurring any consequences besides those specified in the statute.
Inter partes review proceedings for biosimilar products are soaring. Biosimilar makers are taking advantage of IPR proceedings to challenge patents protecting some of the world's most important biologic medicines due to the advantages that these proceedings offer: no standing requirement, no presumption of validity, a lower burden of proof and potentially broader claim construction. More than half of the IPR petitions challenging these patents were filed in fiscal 2017. But the results are mixed, with the Patent Trial and Appeal Board denying a high percentage of the petitions. Many of these patents are ultimately litigated in district court under the U.S. biosimilar statute, the Biologics Price Competition and Innovation Act of 2009 (BPCIA).
On November 13, The Federal Circuit issued a decision affirming a district court judgment that Apotex did not infringe Amgen’s recombinant protein patent in its abbreviated Biologics License Applications referencing Amgen’s Neulasta and Neupogen. Judge James Cohn of the Southern District of Florida ruled in Apotex’s favor in September 2016 after a bench trial. On appeal, the Federal Circuit found sufficient evidence in the record to support the judgment of noninfringement.
In Sandoz v. Amgen, the Supreme Court interpreted the U.S. biosimilars statute, the Biologics Price Competition and Innovation Act (BPCIA), for the first time. The Court held unanimously that provisions of the BPCIA requiring disclosure allowing innovator companies to assess whether their patents are infringed cannot be enforced under federal law. The ruling also allows biosimilar makers to provide notice of commercial marketing long before FDA approval of the biosimilar. The Court’s decision introduces uncertainty into provisions of the BPCIA that many viewed as necessary and enforceable. But, due to the value of certainty for both biosimilar makers and innovators alike in resolving patent disputes for blockbuster biologics, the impact of the Supreme Court’s decision may ultimately be modest.
To read the article by Irena Royzman and Nathan Monroe-Yavneh in Nature Biotechnology, please click here.
Amgen and Genentech have become embroiled in a novel procedural dispute relating to Mvasi, Amgen’s biosimilar of Genentech’s Avastin (bevacizumab). On October 6, in a complaint filed in the Central District of California, Amgen brought an action seeking a declaratory judgment that 27 of Genentech’s patents are not infringed, invalid, and unenforceable. Amgen’s suit appears to be the first post-approval declaratory judgment action brought by a biosimilar applicant under the young U.S. biosimilar statute, the Biologics Price Competition and Innovation Act (BPCIA). Shortly after Amgen filed its declaratory judgment action, Genentech filed its own suit in the District of Delaware, alleging that Amgen had failed to honor promises made during the pre-suit BPCIA process and infringed Genentech’s patents. Amgen then promptly moved to transfer the Delaware case to California. Genentech then filed another complaint in the District of Delaware, followed by another Amgen motion to transfer.
Amgen filed patent infringement claims against Mylan over Mylan’s proposed Neulasta biosimilar. The suit is the latest in a number of litigations over the blockbuster drug.
Following Biosimilar Trial, Jury Awards Amgen $70 Million for Pfizer’s Pre-Approval Infringement of Now-Expired EPO Patent
In one of the first Biologics Price Competition and Innovation Act (BPCIA) litigations to reach trial, a jury on Friday awarded Amgen $70 million in damages for Pfizer’s infringement of one of Amgen’s expired patents protecting Epogen®. The jury found that Pfizer’s subsidiary Hospira, in manufacturing its proposed biosimilar ahead of FDA approval, was not protected by the statutory safe harbor, 35 U.S.C. § 271(e)(1). This action provides an important lesson in the potential value of expired or soon-to-expire patents in BPCIA litigation. Because a biosimilar maker’s pre-approval activity may not be covered by the statutory safe harbor, patents that are expired at the time of approval may still have been infringed.
FDA announced Thursday that it has approved Mvasi (bevacizumab-awwb), Amgen and Allergan’s biosimilar of Genentech’s Avastin (bevacizumab), a monoclonal antibody used in the treatment of a number of different cancers. Mvasi is the seventh biosimilar approved in the United States under the BPCIA and the first biosimilar approved by FDA for cancer treatment. Mvasi was approved for all six indications of Avastin that are not protected by orphan drug exclusivities, with Avastin’s other indications protected by exclusivities expiring in 2021 and 2023.
On August 2, AbbVie sued Boehringer in the District of Delaware, alleging infringement of multiple patents related to AbbVie’s blockbuster biologic Humira (adalimumab). Though AbbVie has “more than 100 issued United States patents” that protect Humira and says that Boehringer infringes 74 of them, AbbVie explains that it was only able to assert 8 of the patents against Boehringer in its complaint. As AbbVie explains, Boehringer was able to limit the scope of litigation to 8 patents by complying with the procedures of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”).
Many biosimilar makers have tried and failed to obtain approval for biosimilar versions of Amgen’s Neulasta (pegfilgrastim), a long-acting version of Amgen’s Neupogen (filgrastim). Coherus BioSciences, Inc. is the latest biosimilar maker to encounter such hurdles. FDA denied Coherus’s biosimilar application in June, pushing any approval of the proposed biosimilar back by at least a year. Coherus was forced to lay off a third of its workforce after FDA’s rejection of the application. On Tuesday, it asked a federal court to stay the BPCIA litigation recently brought against it by Amgen. Coherus seeks to stay discovery until resolution of its pending motion to dismiss to allow it to conserve resources while preparing to resubmit its biosimilar application.
On Thursday, July 13, 2017, FDA’s Oncological Drugs Advisory Committee (ODAC) unanimously recommended approval of biosimilars of two blockbuster cancer drugs. The first, Amgen and Allergan’s ABP-215, is a proposed biosimilar of Roche/Genentech’s Avastin (bevacizumab), a monoclonal antibody used in the treatment of a number of different cancers. The second, Mylan and Biocon’s MYL-1401O, is a proposed biosimilar of Roche/Genentech’s monoclonal antibody Herceptin (trastuzumab), a drug used in the treatment of HER2+ breast and gastric cancer. If, as expected, the drugs receive final FDA approval, each of these drugs will be the first U.S. biosimilar for its respective reference product.
Pfizer’s proposed biosimilar of Amgen’s Epogen® and Johnson & Johnson’s Procrit® (epoetin alfa) is poised to be the first erythropoietin (EPO) biosimilar in the U.S. FDA staff recommended approval of Pfizer’s product as a biosimilar for the four indications of Epogen/Procrit. On May 25, 2017, FDA’s advisory committee agreed with that assessment, but FDA did not approve Pfizer’s product following the meeting. Instead, in a first for biosimilar products, FDA issued a complete response letter in June rejecting Pfizer’s EPO biosimilar application for a second time. Pfizer revealed that FDA did not approve the application after the advisory committee meeting due to FDA’s concerns with a manufacturing site for the EPO biosimilar. Pfizer’s product may not be approved, much less launched, this year due to outstanding manufacturing issues.
On Monday, the U.S. Supreme Court issued its first interpretation of the biosimilars statute, the Biologics Price Competition and Innovation Act of 2009. The BPCIA, part of Obamacare, introduced an abbreviated pathway for regulatory approval of biosimilars, allowing biosimilars to piggyback on the regulatory data of innovator biologics for their approval.
Supreme Court Decides Amgen v. Sandoz: Patent Dance Cannot Be Enforced by Federal Injunction, Notice of Commercial Marketing Can Be Given at Any Time
On June 12, 2017, the Supreme Court decided Amgen v. Sandoz, the landmark case about the meaning of the Biologics Price Competition and Innovation Act (BPCIA). First, the Supreme Court held that no federal injunction is available to force biosimilar applicants to participate in the BPCIA’s patent dispute resolution procedures (a/k/a the patent dance); but it remanded to the Federal Circuit to address whether such an injunction is available under state law. Second, the Court held that under the BPCIA, a biosimilar applicant may provide 180-day notice of commercial marketing before the biosimilar product is licensed, meaning that as a practical matter, the 180-day notice period need not affect the timing of the biosimilar product’s launch.
This post, Part III, of a three-part series (Part I and Part II) on FDA’s interchangeability draft guidance highlights a number of open issues that stakeholders have identified in their comments to FDA. These include the naming and labeling for interchangeable products as well as the relationship between multiple interchangeable products for the same reference product. Biosimilar makers also wanted FDA to make clear that physician-mediated switching is possible for non-interchangeable biosimilar products even if pharmacy-level substitution is not. A number of patient groups, by contrast, expressed concern that payers were in effect mandating pharmacy-level substitution for non-interchangeable biosimilars by taking innovator products off formularies.
This post, Part II, of a three-part series (Part I) on FDA’s interchangeability draft guidance, highlights the key issues that were raised in the stakeholder comments provided to FDA. FDA received 52 comments in total from a variety of stakeholders, including patients, physicians, insurers, innovators and biosimilar makers. The stakeholders were divided in their views in a number of areas. Patient and physician groups and innovators urged FDA to adopt more stringent requirements for interchangeability assessments. Biosimilar makers and insurers, by contrast, generally pressed for a loosening of the guidance provided by FDA as well as clarification that interchangeable biosimilar products were not more similar to the innovator product than the non-interchangeable ones. The comments also raised a number of issues not addressed by the guidance, which will be discussed in the third post in this series.
The comment period for FDA’s draft guidance Considerations in Demonstrating Interchangeability With a Reference Product closed on Friday, May 19, 2017. Innovators, biosimilar makers, patients, healthcare providers and other stakeholders have weighed in on the long-awaited guidance. Interchangeable biosimilars, unlike other biosimilars, may be substituted for the innovator product without the intervention of the healthcare provider who prescribed the innovator product. FDA’s guidance for interchangeable biosimilars is thus particularly important to stakeholders. This post, Part I of a three-part series, provides an overview of the key provisions of the guidance. Parts II and III will focus on the comments from stakeholders and open issues.
Approvals of biosimilar products in Europe continue to outpace those in the United States. 28 biosimilars are currently approved in Europe and five in the U.S. In 2017, the European Medical Agency has approved six biosimilar applications, including applications for biosimilars to two of the best-selling complex biologics, Humira (adalimumab) and MabThera (rituximab). EMA is likely to approve seven more biosimilar applications in the coming months. The Food and Drug Administration in turn has approved one biosimilar this year, and has scheduled an advisory committee meeting for later this month for Pfizer’s proposed biosimilar of Amgen’s EPO (epoetin alfa), which the agency previously rejected. Proposed biosimilars of complex biologics in a number of new classes are pending before both agencies at the same time.
President Donald J. Trump has now been in office for just over one hundred days. Observers have been quick to mark this milestone and assess the new administration’s performance, especially on headline-grabbing issues like immigration and foreign policy. Amidst the hubbub, however, few have commented on how President Trump’s opening moves could affect the multi-billion-dollar biologics industry. President Trump’s actions during his first hundred days on issues like trade, judges, and healthcare have the potential to shape the biologics industry for innovators and biosimilar makers alike for years to come.
In public debates over the Affordable Care Act (ACA), also known as Obamacare, biosimilars are rarely, if ever, mentioned. But the U.S. biosimilar statute, the Biologics Price Competition and Innovation Act (BPCIA), was in fact enacted as part of Obamacare — specifically, as Title VII to the ACA. Although the BPCIA is no longer politically controversial, it could, at least theoretically, be swept up in a blanket repeal of Obamacare, if a bill repealing the ACA did not contain an appropriate carve-out.
A number of biosimilar makers have tried to obtain approval for proposed biosimilar versions of Amgen’s Neulasta (pegfilgrastim), a long-acting version of Amgen’s Neupogen (filgrastim), but have encountered hurdles so far both in the U.S. and Europe.
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.
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