Second Amgen Biosimilar Decision Provides More Clarity

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By John T. Aquino

July 6 — The Federal Circuit's second decision interpreting the biosimilar statute provided more clarity and momentum for the development of U.S. biosimilars, attorneys told Bloomberg BNA July 6.

The ruling in Amgen, Inc. v. Apotex, Inc. by a three-judge panel of the U.S. Court of Appeals for the Federal Circuit ( see related story in this issue), offered additional details on an issue some stakeholders believed was left unclear in Amgen v. Sandoz, its first decision on the Biologics Price Competition and Innovation Act of 2009 (BPCIA) (9 LSLR 828, 7/24/15).

Siegmund (Sige) Gutman, chairman of the life sciences patent practice with Proskauer, Los Angeles, told Bloomberg BNA in a July 6 phone interview, “I think the decision moves the ball forward for everyone on either side of the fence, be it the makers of branded biologics or biosimilar applicants. Any insight into how this complex statute should be applied is helpful.”

More Uncertainty Possible?

In its most recent ruling, the court held that the statute's six-month notice of commercial marketing is mandatory, even if the parties exchange patent-related information ahead of time. The court rejected Apotex's argument that this effectively extends the BPCIA's 12-year exclusivity period to 12.5 years.

But Gutman and others indicated to Bloomberg BNA that the decision's comments on the Food and Drug Administration's ability to issue a temporary license approval to deal with the six months of additional exclusivity may create more uncertainty until the FDA agrees or disagrees with the Federal Circuit's interpretation.

The panel's decision affirms the district court's injunction favoring Amgen, the maker of Neulasta (pegfilgrastim), a bone marrow stimulant that reduces the likelihood of infection in chemotherapy patients.

Unless Apotex petitions for and gets a rehearing or a full court (en banc) hearing, the parties will continue to litigate infringement and patent validity claims, with a bench trial set to begin July 11 in the U.S. District Court for the Southern District of Florida.

Patent Dance Doesn't Help

A biosimilar is a complex, large-molecule biological product that is approved based on a showing that it is highly similar to an already-approved biological product, known as a reference product (RP) or a branded biologic.

Under the BPCIA, a biosimilar applicant can use an abbreviated approval pathway that relies in part on the data the RP sponsor provided to the FDA for approval of the RP. The pathway is similar to the one provided to those making generics of small-molecule, chemically derived drugs under the Hatch-Waxman Act.

The FDA approved the first biosimilar, Sandoz's Zarxio, a biosimilar of Amgen's cancer treatment Neupogen, in March 2015 (9 LSLR 328, 3/20/15). Zarxio's release was delayed by six months as a result of the Federal Circuit's ruling in Amgen v. Sandoz, which held that the exchange of patent information between the RP sponsor and the biosimilar applicant under the BPCIA is optional and that the 180-day notice of commercial marketing under the statute can't begin until the FDA approves the biosimilar.

Gutman said, “Some people had raised the question that the Sandoz decision wasn't entirely clear on the 180-day notice provision because Sandoz hadn't engaged in the patent dance with Amgen over Zarxio and Apotex had done the dance with Amgen over its Neulasta biosimilar. The new panel made it clear that the provision is mandatory and that it doesn't start until the FDA approves the licensure for the biosimilar. The panel said that there was no ‘legally material distinction' to participation in the patent dance.”

The biosimilar applicant can fight an underlying patent as soon as four years after the FDA approves the RP, but the FDA won't give the applicant the benefit of the RP sponsor's efficacy and safety data until 12 years have passed. It is only then that the FDA can license a biosimilar.

No Fractured Court Here

Stacie Ropka of Axinn, Veltrop & Harkrider LLP told Bloomberg BNA in a July 6 phone interview, “It is important to note that it was a different panel from the one that issued Amgen v. Sandoz and it was unanimous. It wasn't the fractured decision we got in Sandoz, with Judges Alan D. Lourie and Pauline Newman agreeing on the 180-days notice provision and Judge Raymond T. Chen disagreeing and Lourie and Chen agreeing that the information exchange was optional and Newman disagreeing. The [Apotex] panel made its position absolutely clear.”

Judges Richard G. Taranto, Evan J. Wallach and William C. Bryson were on the Apotex panel.

Courtenay C. Brinckerhoff, partner and intellectual property lawyer with Foley & Lardner LLP, Washington, told Bloomberg BNA in a July 5 e-mail that the court emphasized that the BPCIA created a “two stage” patent litigation process, and found that the 180-day pre-marketing notice is essential to the second stage, because it “gives the reference product sponsor time to assess its infringement position for the final FDA-approved product as to yet-to-be-litigated patents,” and “gives the parties and the district court the time for adjudicating such matters without the reliability-reducing rush that would attend actions for requests for relief against immediate market entry that could cause irreparable injury.”

Ropka saw the decision as part of biosimilars gaining momentum in the U.S. “And the momentum is feeding on itself,” she said. “The FDA is gaining confidence in its ability to request information, learning what is possible and how good the level of detail in our analyses had become in which you can compare two different molecules. And meanwhile, although gradually, the court is providing better understanding of the statute.”

Will FDA Agree With Federal Circuit?

Having made itself “absolutely clear,” Ropka said, the Federal Circuit created some new uncertainty by “putting the ball in the FDA's court.”

Ropka said, “One new issue that the court raised—the Sandoz court hinted at it but this panel said it straight out—is that if the RP has any of its 12 years of exclusivity left and the FDA indicates before the 12 years are up that it is ready to grant approval for a biosimilar, the panel said it saw no reason why the FDA can't issue a license that becomes effective the day after the 12-year exclusivity period has expired so that the biosimilar applicant is all set to go and doesn't have to wait the 180 days. This is possible because the applicant has been working with the FDA, and it might not need all that much time to approve the biosimilar.”

The question is, Ropka said, does the FDA feel that it has the authority to do this, even though it doesn't say it does in the BPCIA?

Brinckerhoff said, “It will be interesting to see if the FDA interprets and implements §262(k)(7)(A) in line with the Federal Circuit’s suggestion, and if that interpretation is upheld by the U.S. Court of Appeals for the District of Columbia, which is the appellate court most likely to review the FDA’s interpretation of that statute.”

According to Gutman, “This ‘tentative approval' is analogous to what the FDA does for generic drugs under the Hatch-Waxman Act. That statute does have a 30-day stay, which can prompt tentative approvals. The FDA has been doing this for a long time. It's no stranger to it. That said, there is nothing in the BPCIA that allows the FDA to do this, so it will be interesting to see if it feels it has the authority.”

Applicants Control Timing

A Biotechnology Innovation Organization spokesman offered BIO's reaction to the Apotex decision to Bloomberg BNA in a July 6 e-mail, addressing Apotex's argument that Amgen's interpretation of the BPCIA gives RPs an additional six months of exclusivity.

“Today’s Federal Circuit decision in Amgen v. Apotex in no way changes the innovator’s 12-year data exclusivity period under current law. The ruling merely ensures that biologic innovators have at least 180 days to review potential patent infringements before a competitor brings to market a product based on their innovation. Far from giving innovators ‘an extra six months,’ as some in the media have asserted, the court’s opinion instead emphasizes the control biosimilar applicants have over the timing of their applications and market launch,” the e-mail said.

According to BIO, the court explained that biosimilar applicants need not encounter any delays beyond the expiration of the 12-year data exclusivity period, if they submit their regulatory applications in a timely manner.

“According to the court’s decision, a biosimilar maker is not precluded from receiving FDA approval and giving the required six-month notice of commercial marketing sufficiently in advance of the 12-year mark to avoid any delays. In this way, the decision creates a healthy incentive for biosimilar applicants to submit their regulatory applications early, and to engage in a fair and timely patent resolution process prior to the expiration of innovator exclusivity and biosimilar launch.”

To contact the reporter on this story: John T. Aquino in Washington at

To contact the editor responsible for this story: Randy Kubetin at

For More Information

The court's decision is at

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