FDA Approves Amgen's Humira Biosimilar, Release Not Until 2017

Life Sciences Law & Industry Report connects the dots among the many disciplines that make up the burgeoning life sciences industry, with biweekly updates on current regulatory, legislative,...

By John T. Aquino

Sept. 26 — Amgen Inc. won the FDA's approval Sept. 23 for its Amjevita as a biosimilar of AbbVie's blockbuster rheumatoid arthritis drug Humira (adalimumab), but its release could be delayed.

This is the Food and Drug Administration's third approval of a biosimilar this year and its fourth overall, suggesting a quickening approval pace for these less expensive versions of biologic drugs.

It's also a role reversal for Amgen, which has been the brand or reference product sponsor (RPS) of two of the four approved biosimilars—Sandoz's Zarxio (filgrastim-sndz), a biosimilar of Amgen's cancer treatment Neupogen, and Sandoz/Novartis's Erelzi (etanercept-szzs), a biosimilar of Amgen's arthritis drug Enbrel.

Big Biopharma Taking Lead

“This is the world Congress envisioned when they passed the Biologics Price Competition and Innovation Act (BPCIA) into law, and the world the Federal Trade Commission predicted when it produced a study that major biotech and pharma companies would be at the forefront of biosimilar production (as opposed to traditional generic drug companies),” Kevin E. Noonan of McDonnell Boehnen Hulbert & Berghoff LLP, Chicago, told Bloomberg BNA in a Sept. 26 e-mail.

And the products aren't surprising, Noonan wrote, in view of the companies' place in the biologic marketplace and the experience some of them have had in Europe. The “low-hanging fruit” of biologic drugs that are long past their statutory exclusivity periods should lead to several additional biosimilar drugs in the next five to 10 years, he said.

“The true test of whether the law works will be with ‘next generation' drugs having the full 12 years of exclusivity, as will the question of whether the 180-day notice of intent to market (as decided by the Federal Circuit) adds an additional 6 months of exclusivity (subject to Supreme Court review perhaps as early as this term),” Noonan added.

Amjevita Release May Be Delayed

But, even with regulatory approval in hand, the road ahead for Amjevita may not be straight and short.

The FDA's approval was issued against the backdrop of the agency's denial the same day of an AbbVie citizen petition that the FDA not accept for review or approve Amgen's Amjevita on constitutional grounds. AbbVie could appeal the denial in court.

Also, an AbbVie patent infringement lawsuit against Amgen concerning Amjevita in the U.S. District Court for the District of Delaware (10 LSLR 17, 8/19/16) could delay Amjevita's release well into 2017.

AbbVie is trying to extend its exclusivity for Humira (adalimumab), which accounted for 61 percent of its 2015 global revenue and whose sales grew 17 percent in the second quarter this year to $4.15 billion.

Studies Support Biosimilarity

A biosimilar is a biological product that is approved by the FDA based on a showing that it is highly similar to an already approved biological product, known as a reference product (RP), or brand biologic. The BPCIA, part of the Affordable Care Act, created a streamlined approval process for biosimilars. On further review by the FDA, the biosimilar can be designated as interchangeable, which means that a pharmacist can substitute the biosimilar for the RP without physician approval.

According to the FDA's press release, Amjevita is approved for these indications in adults: moderately to severely active rheumatoid arthritis; active psoriatic arthritis; active ankylosing spondylitis, an arthritis of the spine; moderately to severely active Crohn's disease; moderately to severely active ulcerative colitis; and moderate to severe plaque psoriasis. Amjevita is also approved for moderately to severely active polyarticular juvenile idiopathic arthritis in patients four years or older.

In a press statement, Sean E. Harper, Amgen's executive vice president of research and development, said, “This milestone exemplifies our ongoing dedication to the development of high quality biologic medicines.” He noted that Amjevita's approval was based on a comprehensive data package supporting biosimilarity to adalimumab comprising analytical, nonclinical, pharmacokinetic and clinical data, including results from two phase III studies conducted in moderate-to-severe plaque psoriasis and moderate-to-severe rheumatoid arthritis patients.

Patent Infringement Alleged

AbbVie's lawsuit filed in August in the District of Delaware alleges that Amjevita infringes 10 AbbVie patents ( AbbVie, Inc. v. Amgen, Inc., D. Del., No. 16-666, complaint filed 8/4/16).

Amgen responded in a court filing that it intended to comply with the 180-day notice of commercial marketing provision of the BPCIA, which it would submit to AbbVie and which would push the release of Amjevita to at least March 2017.

AbbVie indicated that it was prepared to sue Amgen for infringement of 51 other AbbVie patents once it received the notice of commercial marketing, which could delay the Amjevita release past March.

Citizen Petitions

In its 2012 citizen petition, AbbVie asserted claims that permitting a biosimilar of a biologic that was licensed before March 23, 2010, when the BPCIA was enacted, would constitute a taking under the Fifth Amendment to the Constitution (7 LSLR 195, 2/22/13). According to AbbVie, it would have reasonably expected before that date that its trade secrets and confidential information in the Humira biologics license application (BLA) wouldn't be used to the benefit of a competitor.

In denying the petition, a Sept. 23 letter signed by Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research (CDER), said, “The Fifth Amendment does not protect information that Abbott [AbbVie's predecessor-in-interest of Humira] describes as trade secrets but that was available for public disclosure under FDA's information disclosure regulations after the Agency approved the Humira BLA in 2002. Such publicly available information cannot satisfy the second element under the UTSA [Uniform Trade Secret Act] definition of a trade secret, i.e., that the information ‘is the subject of efforts that are reasonable under the circumstances to maintain its secrecy'” because the government was “without a mechanism to ensure that secrecy is maintained.”

Woodcock added, “Because the analytical, preclinical, and clinical data submitted by Abbott were available for public disclosure immediately following the approval of the Humira BLA, they are not property entitled to protection under the Fifth Amendment.”

AbbVie has filed other citizen petitions that are pending with the FDA related to a Humira biosimilar. On June 2, 2015, it asked that the FDA require labeling that describes how a biosimilar is different from the RPS, including whether it is designated interchangeable. On Dec. 16, 2015, the company asked the FDA to find a biologic product interchangeable with a reference product (RP) only if it is interchangeable for every approved use of the RP.

To contact the reporter on this story: John T. Aquino in Washington at jaquino@bna.com

To contact the editor responsible for this story: Randy Kubetin at rkubetin@bna.com

For More Information

The FDA's denial of AbbVie's petition is at http://src.bna.com/iUd.

Copyright © 2016 The Bureau of National Affairs, Inc. All Rights Reserved.