FDA Advisory Panel Favors Celltrion's Biosimilar of J&J Drug

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

Feb. 9 — The FDA's Arthritis Advisory Committee Feb. 9 voted 21-3 in favor of a biosimilar of Johnson & Johnson's rheumatoid arthritis treatment Remicade, which, if the FDA approves it, would be the second biosimilar approved in the U.S. and the first of a monoclonal antibody.

The Food and Drug Administration advisory panel voted for Korea-based Celltrion Inc.'s CT-P13 as a biosimilar for Remicade's eight indications, which include RA, plaque psoriasis and Crohn's disease.

The committee's discussion was extensive and raised questions about the extrapolation of data to justify approving the drug for all of Remicade's indications and about the biosimilar approval process itself.

Mary E. Maloney, professor of medicine at the University of Massachusetts Medical School in Worchester, Mass., said, “We are scientists, and we live by the evidence. We're being asked to live by extrapolation. That's good for our patients in giving them more, less expensive access to these biologics, It does, however, increase risk. But the alternative is that we should all go home. The purpose of biosimilars is the benefit to the public health.”

The FDA doesn't have to follow the committee's recommendations. An FDA spokesman told Bloomberg BNA in a Feb. 9 e-mail that the agency would take the committee's vote, as well as the comments from committee members, into account when making an approval decision.

An FDA staff report issued Feb. 5 also recommended CT-P13's approval .

Remicade's $4.5 Billion in U.S. Sales

Biosimilars, which are large and complex molecules, are comparable to generic versions of chemically derived, small-molecule drugs, although the approval process is more demanding, and cost savings for biosimilars are expected to range from 15 percent to 30 percent compared to the 70 percent to 90 percent for conventional generic drugs.

FDA approval of a biosimilar means it is highly similar to a previously approved biologic, known as the reference product (RP) and with no clinically meaningful differences.

Monoclonal antibodies are made by identical immune cells that are clones of a unique parent cell and that can specifically bind to a substance to detect or purify it. They are used in cancer treatments.

Remicade (infliximab) generated $4.45 billion in U.S. sales last year for J&J, according to data compiled by Bloomberg, and competes with AbbVie Inc.'s Humira. CT-P13 was authorized for sale in Europe by the European Medicines Agency in 2013, where it is called Remsima.

Some patient group representatives expressed the desire to have randomized clinical studies for each indication. Committee members noted that this would defeat the purpose of the abbreviated approval pathway for biosimilars, which largely relies on the data used for the RP in its approval.

Original Biologics Fight to Retain Market Share

The FDA has approved just one biosimilar to date under the Biosimilars Price Competition and Innovation Act's (BPCIA) abbreviated approval pathway. Zarxio, Sandoz's biosimilar of Amgen's cancer treatment Neupogen, was approved nearly a year ago.

Amgen has applied to the FDA for approval of a biosimilar version of AbbVie's Humira .

Zarxio has been the subject of litigation between Amgen and Sandoz (part of Novartis) over interpretations of the BPCIA, which resulted in Zarxio's release being delayed months later than Sandoz had planned .

Biologics have existed so far in the U.S. without competition, and delays in the release of a biosimilar benefit the RP sponsor. The BPCIA also outlines a mechanism for the RP sponsor to sue the biosimilar applicant for patent infringement.

Concerns About Extrapolations

The committee's meeting on CT-P13 was originally scheduled for March 15, 2015, but it was postponed because the FDA was awaiting additional information from Celltrion.

In its presentations to the committee, Celltrion said it had studied CT-P13 in RA and ankylosing spondylitis, a disease that can cause some of the vertebrae in the spine to fuse together. The company also provided information to support extrapolation of the data on the two diseases to gain approval for the other six conditions Remicade is approved to treat. FDA staff members also made presentations about their approval recommendation.

During the open public hearing session, Jay Siegel, J&J's chief biotechnology officer and head of scientific strategy and policy, noted the company's support of a biosimilar abbreviated approval pathway, but expressed J&J's concerns about the data extrapolations in Celltrion's submission.

“Differences between arthritides [inflammation of joints] and irritable bowel disorder [IBD] impacting extrapolations occur not only in mechanics of action but also in PK [pharmacokinetics—the absorption, distribution, metabolism and elimination of drugs from the body], site of action and other factors,” Siegel said.

He also said that there are differences in function between Remicade and CT-P13 that are believed to be important to the treatment of IBD with Remicade.

Concerns About Switching

A number of speakers at the open public session expressed concern about how the FDA approves biosimilars in general.

Larry LaMotte, vice president of public policy at the Immune Deficiency Foundation and a Patients for Biologic Safety and Access member, noted that the FDA has yet to issue final guidance on a range of issues that will affect patient safety including naming, labeling and indication extrapolation.

“Of all the stakeholders in this process, patients have the most at risk since they are the people whose lives and bodies will literally depend upon the safety and effectiveness of these new drugs,” LaMotte said.

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

To contact the editor responsible for this story: Lee Barnes at lbarnes@bna.com

For More Information