amgenOn September 23rd, 2016, the US Food and Drug Administration (FDA) announced that the Agency licensed the fourth biosimilar biological product under the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”). The FDA has approved adalimumab-atto (Amjevita by Amgen, Inc.), a biosimilar to adalimumab (Humira® by AbbVie, Inc. which was originally approved by the FDA in December 2002), for the treatment of multiple inflammatory diseases1, 2. The licensure of the Humira® biosimilar by the FDA follows PHS Act Section 351(k) licensures for ERELZI (etanercept-szzs) (BLA 761042; licensed on August 30, 2016), INFLECTRA (infliximab-dyyb) (BLA 125544; licensed on April 5, 2016), and ZARXIO (filgrastim-sndz) (BLA 125553; licensed on March 6, 2015)1.

The biosimilar has been approved for the treatment of adults with 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. In addition, adalimumab-atto is approved for children aged 4 years or older with moderately to severely active polyarticular juvenile idiopathic arthritis. A biosimilar is a drug that has been demonstrated to be highly similar to another approved drug with no clinically meaningful differences in “safety, purity and potency,” the FDA explained2. The FDA’s approval follows a review of data including structural and functional analyses, animal study data, human pharmacokinetic and pharmacodynamics analyses and clinical immunogenicity data, as well as clinical safety and effectiveness data supporting the drug’s biosimilarity to adalimumab. The FDA has approved adalimumab-atto (Amjevita) as a biosimilar and not as an interchangeable drug with Humira®.

Amgen’s Humira® biosimilar is now officially FDA-approved. It has an official brand name, Amjevita. However, that doesn’t mean it will be used anytime soon by healthcare practitioners in the US. That may be the scenario because of 2 reasons: Firstly, a required 180-day notice period means that at best, the California based Amgen could launch its FDA approved Humira® biosimilar at the earliest next March, 2018. Secondly, AbbVie the innovator pharmaceutical company which manufactures and distributes the $14 billion Humira®, has sued for patent infringement, claiming that Amgen’s biosimilar violates 10 individual AbbVie patents claimed by AbbVie regarding Humira®. As usual with these sorts of lawsuits, AbbVie also asked the court to block Amgen’s drug if and when the FDA issued an approval3. It was all but a foregone conclusion that the agency would approve Amjevita when it received unanimous support of an FDA advisory panel in June. By a 26-0 vote, the committee voted to recommend Amgen’s biosimilar for seven of Humira’s® clinical indications3

Still, the biosimilar approval process is a nascent one, as Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, pointed out in the FDA’s approval announcement. Amjevita is the fourth biosimilar to win the agency’s blessing. “The biosimilar pathway is still a new frontier,” Woodcock said.3 Future drug applications attempting to follow the biosimilar approval pathway offers clues to those biosimilar drugs hoping to follow this evolving regulatory pathway. The Humira patent case presents a delay long past March, depending on the court’s decision on an injunction and AbbVie’s all-but-certain appeal. With $14 billion in sales at stake, AbbVie has been working to shore up its Humira IP, and the company has repeatedly said it believes it can hold off biosimilars until 20223.

“Humira is protected by many patents covering all aspects of its manufacture, formulation and indications and the patents are the result of AbbVie’s investment in biologic innovation and the unique attributes of Humira,” company spokesman Greg Miley told FiercePharma earlier this year3. To that end, AbbVie is not only suing Amgen to defend those 10 Humira patents, but also threatening to follow up with more court challenges. In its complaint, AbbVie claims that Amgen’s product infringes 51 more patents as well. Amgen’s “blatant infringement” should be stopped, AbbVie said 3.

Despite all the legal machinations certainly to follow the approval of this biosimilar to Humira®, the approval Amjevita is associated with the side effect profile and serious labeling that accompanies Humira’s labeling. The most serious known adverse events associated with adalimumab-atto (Amjevita) are infections and malignancies. The most frequently expected adverse events are infections and injection-site reactions. Additionally, as with adalimumab, adalimumab-atto (Amjevita)is approved with the FDA serious boxed warning about increased risk for serious and sometimes fatal infections. The boxed warning also cautions that lymphoma and other, sometimes fatal, malignancies have occurred in children and adolescents treated with tumor necrosis factor blockers, including adalimumab products. The FDA requires adalimumab-atto (Amjevita) to be dispensed with a patient medication guide that provides important information about the drug’s uses and risks.

Readers of this blog are highly encouraged to read and review the provided links/references below as well as multiple sources of information in the public domain related to issues regarding the approval of biosimilars based on the scientific and clinical merits as well as the complex legal issues surrounding the controversial biosimilar approval process.