Remicade Biosimilar FDA Panel Vote Shows How It Can Be Done

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By John T. Aquino

Feb. 10 — An FDA advisory panel's vote in favor of a monoclonal antibody biosimilar that can be used in cancer treatments is good news because it shows that it's possible to generate the type of data that would lead to such a favorable decision, an attorney told Bloomberg BNA.

The Arthritis Advisory Committee for the Food and Drug Administration voted on Feb. 9 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 (mAb) .

“Until this happened, we didn't know if an FDA committee would approve biosimilars of any mAbs, which are so much more complex than the simple, straightforward protein named Zarxio, the first biosimilar FDA approved, which also had a lot of data behind it from Europe,” Stacie Ropka, counsel at Axinn Veltrop & Harkrider, Hartford, Conn., told Bloomberg BNA in a Feb. 11 phone interview. The FDA approved Zarxio as a biosimilar of Amgen's cancer treatment Neupogen in March 2015 .

The committee 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.

“Now we know that it is possible to generate the type of data that an FDA committee and, prior to that, the FDA staff, would accept and that allows the extrapolation of data from one disease to another, something that just a few years ago was greeted with skepticism,” Ropka said.

“If nothing else,” she added, “it's good news because of the technological advances that allow us to characterize a molecule [that] will lead to better medicine.”

While excitement as a result of the committee's decision was high, there was also an acknowledgement, reflecting comments made during the hearing by committee members and the public, that all stakeholders need to be educated about biosimilars.

If Approved, 2016 Launch

The FDA doesn't have to accept the committee's recommendation, although, as Ropka noted, “Historically, you'd expect them to approve it based on the committee's and the FDA staff's recommendations.” A decision is expected in early April.

If approved, the biosimilar would be marketed in the U.S. by Pfizer, which acquired Hospira, Celltrion's collaboration partner, in 2015 .

Jenny Alltoft, global biosimilar head at Pfizer, said in a statement, “We look forward to the FDA's continued review and, while awaiting its decision and certain other factors, we are moving forward with the preparation of our launch plans for 2016.”

Bloomberg Intelligence company analyst Elizabeth Krutoholow wrote in a report on CT-P13 that, if it is approved, using Zarxio's 15 percent discount from Neupogen as a proxy, Celltrion could price CT-P13 at $760 a vial and J&J could stand to lose about 10 percent to 20 percent of its U.S. Remicade business, using the experience of Merck, which has marketing rights to Remicade in Europe.

Pat Lucy, chief business officer of PFEnex, a San Diego-based biotechnology company and biosimilar developer, told Bloomberg BNA in a Feb. 11 phone interview that the advisory committee's recommendation was a great advance for biosimilars in the U.S. and evidence of the FDA's growing support for them.

“This is particularly true because mAbs are very complex and more variable than other biologics, even batch to batch, and the FDA was able to work through that,” Lucy said. “There was very thorough work done by Celltrion and the FDA staff. The committee's recommendation for extrapolations was a grand slam. We in the industry were monitoring the issue of extrapolations, which were approved in Europe for CT-P13 , but in Canada they were not .”

Uncertainty About Extrapolations

But the committee hearing also demonstrated uncertainty among some members as to whether or not extrapolations of data for treatment of one disease indication can support approval of treatment for another indication.

The vote was 21 to 3, although some of the “yes” votes had caveats. Several committee members said they voted “yes” out of the hope that the abbreviated Biologics Price Competition and Innovation Act approval process relying on data used by the original biologic developers in obtaining FDA approval would lower development costs and therefore reduce prices.

Groups speaking at the meeting who represented patients who use biologics said they were grateful for the prospect of less expensive versions. But they also indicated they had some misgivings that the biosimilars would, under the BPCIA, only be “highly similar” to the original biologic and that every indication of the biosimilar wouldn't necessarily receive its own clinical trial.

Jay Siegel, chief biotechnology officer and head of scientific strategy and policy for J&J, which may lose market share when a less expensive biosimilar reaches the market, criticized the extrapolations of data used by Celltrion.

Siegel, who spoke at the hearing, said in a statement released the next day, “We believe that the data to date, absent of direct comparisons of CT-P13 and Remicade in patients with inflammatory bowel disease, leave uncertainty about whether differences in safety or efficacy may emerge for patients. We appreciate the discussions at today’s hearing, and note that some of the advisors—who voted on either side of the question—share our concerns regarding residual uncertainty about the use of CT-P13 in IBD. We hope that FDA carefully considers both our detailed written testimony and the concerns voiced today on extrapolation regarding CT-P13 in IBD.”

Analysts Rattled, Litigation Ongoing

Worries about what was said at the hearing also rattled investment analysts.

Thomas Shrader, an analyst at Stifel Nicolaus, wrote the day after the committee vote that the hearing revealed “a gap” between the FDA’s understanding of the biosimilars approval pathway and the way physicians and patients perceive it. Small differences between the biosimilar and the reference product could lead to “major push back from physicians and patients” who doubt the biosimilar's safety and quality, and these concerns may reduce biosimilar use in “extrapolated indications,” Shrader said.

Ongoing litigation may delay the release of CT-P13.

J&J's Janssen Biotech Inc. March 6, 2015, alleged in a lawsuit filed in the U.S. District Court for the District of Massachusetts that Celltrion's Remicade biosimilar infringes six patents owned or licensed by Janssen and that Celltrion violated the mandatory procedures of the BPCIA requiring an exchange of manufacturing information and refused to participate in the mandated dispute resolution procedures .

Requires Education, Fixing CMS Coding

Lucy said about comments made during and after the hearing, “I think that this comes down to a matter of education on a variety of levels. It's incumbent on the FDA to educate the public on biosimilars and on the product sponsors to give more targeted education about the product. There are four stakeholders who need to be educated: the prescribers, the payers, the patients and the policymakers. The education need cannot be overstated.”

He noted that at a Feb. 4 hearing of the House Energy and Commerce Subcommittee on Health, Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, indicated that the agency had received no additional funding for its efforts on biosimilars after the BPCIA was passed, and that the fees it's collecting that can support its efforts lag behind the work .

“An appropriation from Congress, which was brought up at the hearing by Rep. Frank Pallone Jr. (D-N.J.), would enable the FDA to issue biosimilar guidances on interchangeability, naming and labeling, which will make both patients and doctors more comfortable about biosimilars,” Lucy said.

But another concern is the Centers for Medicare & Medicaid Services and its policies affecting reimbursement for biosimilars. “At the hearing, it was clear that everyone was in agreement on this except the CMS,” Lucy said. “That needs to be fixed. You could see at the advisory committee meeting that committee members and patient groups were struggling with the issue of pricing, and that comes back to the CMS coding.”

The CMS announced in November that its policy was to bundle all biosimilars of a biologic reference product into one code and the reference product into another, with the reimbursement price based on an average sale price of all of the biosimilars .

“If every biosimilar has an individual code, the biosimilar developer can control its own destiny by adjusting the price,” Lucy said.

Biosimilars Ready to Explode?

Lucy quoted Woodcock at the subcommittee hearing as saying that the biosimilar space is ready to explode.

BI's Krutoholow wrote in a separate report on the U.S. biosimilars market that the FDA will review several more biosimilar applications in the U.S. in 2016, possibly ushering in Apotex's biosimilars for Amgen's Neulasta and Neupogen, and Novartis's biosimilars for Pfizer's Enbrel and Amgen's Neulasta.

Lucy said, “A lot of these things that we're talking about now will be sorted out in the process. It was clear to us that the FDA was very supportive of the Celltrion application. And our experience with the FDA on biosimilars is that they have been very informative, clear and consistent.”

Ropka concluded, “After the approval of CT-P13 by the advisory committee and the FDA staff, whatever the FDA ultimately decides, it is clear that the FDA feels it knows what questions to ask. And this may encourage applicants who can now see a path forward.”

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

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

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