Second U.S. Biosimilar Approval Shows FDA's Confidence

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By John T. Aquino

April 6 — The FDA's approval of the second U.S. biosimilar was a very big step for these less-expensive biologic drugs because it shows the agency is comfortable reviewing more complex biosimilars, an attorney and pharma association said.

The Food and Drug Administration approved Pfizer's and Celltrion's Inflectra as a biosimilar of Johnson & Johnson's blockbuster arthritis treatment Remicade (infliximab) on April 5 . The approval came a year and two days after the agency approved the first U.S. biosimilar under the Biologics Price Competition and Innovation Act (BPCIA)—Zarxio, Sandoz's biosimilar of Amgen's cancer treatment Neupogen .

“This signals that the Food and Drug Administration has confidence in its approval process and confidence to okay something as complex as a biosimilar of a monoclonal antibody as well as extrapolations across seven indications of the original biologic or reference product,” Stacie Ropka, counsel at Axinn Veltrop & Harkrider, Hartford, Conn., told Bloomberg BNA in an April 6 phone interview. Zarxio is a biosimilar of a relatively straightforward protein ; Remicade has seven indications, and Inflectra may be used for any of them.

Remicade generated $4.5 billion in U.S. sales in 2015 for J&J, competing with AbbVie Inc.'s blockbuster drug Humira. Amgen Inc. has applied to the FDA for approval of a biosimilar version of Humira.

Big Step, Some Concerns

Ropka said, “Since the FDA now knows the type of data it requires for biosimilars of both straight-forward and complex biologics, I would think it would say to other biosimilar applicants, ‘This type of data has worked for us.' That is not to say that it's still not going to be on a case-by-case basis. But there's no denying this is a big step forward for biosimilars in that it should encourage other biosimilar developers.”

Mark Merritt, president and chief executive officer of the Pharmaceutical Care Management Association (PCMA), said in a statement, “The FDA is taking important steps toward approving more biosimilars in the United States. Increasing competition through the approval of brand and generic drug competitors is the key to lowering prescription drug costs for consumers, employers, government programs and others. To further advance the use of biosimilars, the FDA should finalize an interchangeability policy that will allow for greater patient access to these important drugs.”

But not everyone was excited about the FDA's decision.

J&J issued a statement comparing Remicade to its new competitor, Inflectra, noting that Inflectra hasn't yet been found to be interchangeable, and a patients' group expressed concern that the FDA continues to approve biosimilars without having first put in place critical policies that safeguard patients.

Market Availability

How quickly Inflectra gets to market is unclear. In the stipulation of dismissal of J&J's litigation against Celltrion concerning Inflectra, Celltrion indicated to the U.S. District Court for the District of Massachusetts on March 22 that it wouldn't sell the biosimilar in the U.S. before June 30, which is when the patents-at-issue will expire.

The release of Inflectra may also depend on a decision by the U.S. Court of Appeals for the Federal Circuit in Amgen, Inc. v. Apotex, Inc., for which a three-judge panel heard oral arguments on the day before the FDA's approval of Inflectra . The question in that case is whether a biosimilar applicant always has to give 180 days' notice to the original or reference product sponsor, starting on the day the FDA approves the biosimilar, of its intent to commercially market the product. If the Federal Circuit concludes that the notice is always required, that could push Inflectra's release date to October.

J&J, Patients' Group Reactions

A biologic is a complex, large molecule, such as a monoclonal antibody or a cell-signaling protein. A biosimilar is analogous but not the same as a generic of chemically derived drugs. While a generic is identical to the originator drug, a product designed to resemble an FDA-approved biologic can only be approved by the FDA as biologically similar to the reference product with no clinically meaningful differences, and, on further FDA approval, as interchangeable without the approval of a physician.

The day of the FDA announcement, Jay Siegel, J&J's chief biotechnology officer and head of scientific strategy and policy, pointed out in a statement that “Celltrion’s infliximab-dyyb is a biosimilar but not identical to Remicade.”

“It is important to note,” he said, “that the FDA has not approved Celltrion’s infliximab-dyyb as being interchangeable with Remicade. For FDA to determine a biosimilar is interchangeable with its reference product, a manufacturer must demonstrate that the biosimilar is expected to produce the same clinical result as the reference product in any given patient. In addition, the manufacturer must demonstrate the risk of alternating or switching between the reference product and biosimilar is no greater than the risk of using the reference product,” Siegel wrote.

Patients for Biologics Safety & Access (PBSA), a coalition of 23 national patient advocacy organizations dedicated to protecting patient access to safe and effective biologics, also expressed some concerns. In a statement, the group said, “Regardless of the merits of the drug in question, patient advocates are concerned that the FDA now has approved a second biosimilar drug without having first put in place critical policies that safeguard patients. To date, and contrary to its own policy of transparency, FDA has not issued final guidance on a range of key issues that will impact patient safety including interchangeability, product labeling and naming and approval relying on indication extrapolation.”

The FDA last year released three final guidances on quality considerations, scientific considerations and questions and answers about biosimilars and the new law .

The PBSA said that while U.S. communities are eager for new and affordable treatments, patients with rare and chronic diseases are keenly aware of the possible risks associated with biosimilars.

“To date, we have not been satisfied with the extent FDA has included the patient voice in the formation of the biosimilars approval process,” the PBSA said.

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

To contact the editor responsible for this story: Lee Barnes at

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