Category: BPCIA

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.

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.

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.  

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).

On June 20, 2016, the full Federal Circuit declined to rehear Acorda Therapeutics Inc. v. Mylan Pharms. Inc., 817 F.3d 755 (Fed. Cir. 2016) en banc. Acorda affirmed two District of Delaware decisions finding specific jurisdiction over Mylan Pharms., an out-of-state ANDA filer, based on its plans to sell its proposed generic drugs in Delaware. After the Supreme Court’s decision in Daimler AG v. Bauman, 134 S.Ct. 746 (2014), Mylan has argued that it could only be sued in its home state of West Virginia in ANDA cases since future sales of its proposed generic drugs could not confer specific jurisdiction in Delaware.  The Federal Circuit disagreed.  Under Acorda, plaintiffs in ANDA cases as well as in cases brought under the Biologics Price Competition and Innovation Act (BPCIA) can bring suit in their forum of choice based on future sales of proposed generic or biosimilar products so long as considerations of fairness, such as efficiency or undue burden, do not render jurisdiction in the forum unreasonable.  

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.

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.

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.  

The Federal Circuit affirmed two decisions by the District of Delaware to assert personal jurisdiction in ANDA cases over West Virginia-based manufacturer Mylan.  Mylan had argued that it could only be sued in West Virginia in ANDA cases post the Supreme Court's decision in Daimler AG v. Bauman, 134 S.Ct. 746 (2014) because such cases are litigated before actual sales of its generic drug product are made in Delaware (and elsewhere).  The Federal Circuit grounded its rejection of Mylan's approach on Mylan's filing of its ANDAs with the clear intent to market its proposed generic drugs in Delaware upon FDA approval, as well as the injury Mylan would cause in Delaware through such sales.  Under the Federal Circuit's decision, plaintiffs in ANDA and BPCIA cases can obtain jurisdiction over defendants in their forum of choice based on defendants' regulatory filings with the intent to market their proposed products so long as consideration of fairness, such as undue burden on defendants, do not render jurisdiction in the chosen forum unreasonable.

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.

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.

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.

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.

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).

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.

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.  

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.

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).    

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.

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.

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.

Defendants in Hatch-Waxman cases continue to contest personal jurisdiction outside of their "home" state, in reliance on the Supreme Court's decision in Daimler AG v. Bauman.  Most district courts have rejected such arguments, and found that jurisdiction is proper in the patent owner's preferred forum based on consent-by-registration jurisdiction or specific jurisdiction. Both theories of personal jurisdiction are on appeal before the Federal Circuit, and oral argument is likely to occur early in 2016. The lessons learned in the Hatch-Waxman context will provide guidance for litigation under the BPCIA. 

The FDA has issued a long-awaited draft guidance document and proposed rule on the nonproprietary names for biosimilar medicines.  FDA proposes to give biosimilars a “core name” shared with all related biological products and a four-letter suffix, unique to each product.  The four-letter suffix, unlike the placeholder name for the first US biosimilar, Sandoz’s Zarxio (filgrastim-sndz), does not identify the product’s manufacturer.  Instead, it is a random collection of four letters, “devoid of meaning.”  Patient groups and physicians have applauded FDA’s use of unique suffixes to differentiate biological products but innovator companies prefer meaningful suffixes, such as the one for Zarxio, and biosimilar manufacturers argue for no distinguishing names at all.  

Today, Sandoz (a Novartis subsidiary) launched the first biosimilar approved under the BPCIA: the cancer drug Zarxio (filgrastim-sndz), which is a biosimilar version of Amgen’s Neupogen.  The launch follows the Federal Circuit’s decision enjoining Sandoz from launching Zarxio for 180 days and the court’s recent denial of Amgen’s emergency motion to extend the injunction pending Amgen’s and Sandoz’s cross-petitions for rehearing en banc.