FDA's First Biosimilar Approval Greeted With Optimism; Naming, Pricing Still Issues

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By John T. Aquino

March 9 — Attorneys greeted the Food and Drug Administration's first approval of a biosimilar using the abbreviated approval pathway under the Biologic Price Competition and Innovation Act (BPCIA) as a good first step but cautioned that the agency picked “low-hanging fruit.”

“What it shows is that biosimilar approval can be achieved for a relatively simple protein that has been on the market as a brand in the U.S. and as a biosimilar in Europe for a while,” Stacie Ropka of Axinn, Veltrop & Harkrider, Hartford, Conn., told Bloomberg BNA in a March 9 phone interview. Pending abbreviated biologics applications (aBLAs) for more complex drugs may find a longer approval road at the FDA, Ropka said.

Eli A. Loots, of Knobbe Martens, San Francisco, agreed that the “low-hanging fruit” was the right perspective and raised the issue of pricing, which, he said, could determine how many biosimilars will be around in 10 years.

Novartis AG's biosimilar version of Amgen Inc.'s biologic cancer drug Neupogen, which Novartis will call Zarxio, won FDA approval March 6 under the BPCIA, which is part of the Affordable Care Act. Neupogen generated $1.2 billion in sales in 2014 as a therapy to help increase cancer patients' white blood cell counts and fight infections. Biosimilars are similar but not identical to the brand biologic because biologics are manufactured from living organisms rather than chemically-derived.

According to a RAND Corp. report in November 2014, biosimilars are predicted to cut prices of biologics from 10 percent to 50 percent, considerably less than the 80 percent discounts chemically derived generic drugs offer compared to brand name drugs. Goodwin Procter's “Biosimilars: A Guide to Regulatory and Intellectual Property Issues” says that in Europe, the average cost to the consumer of a biosimilar is 15 percent to 30 percent less than the brand or reference biologic product.

Approved, But Release Delayed

The FDA approval clears the regulatory hurdle for the release of Zarxio but not the court challenges. Citing that Zarxio could be approved as early as March 8, Amgen urged the U.S. District Court for the Northern District of California to order Novartis's Sandoz unit not to begin marketing its Zarxio. 

According to Amgen, Sandoz deliberately failed to provide Amgen with a copy of its aBLA and the accompanying information describing its process for manufacturing the biosimilar product within 20 days of receiving notification that the FDA had accepted its application.

California-based Amgen alleged that Sandoz is illegally avoiding its obligations under the BPCIA with its aBLA for Zarxio, contending that the law's requirements at issue are mandatory, while Sandoz argues that the requirements are optional. Amgen accused Sandoz of engaging in unfair competition under California law and conversion of Amgen's Neupogen license and patent infringement and seeks to enjoin Sandoz from commercially marketing its product under the BPCIA until the company meets its statutory obligations under the law.

The court hasn't yet ruled on Amgen's motion for a preliminary injunction. Novartis has agreed to delay selling the biosimilar in the U.S. until the lawsuit with Amgen is resolved or until April 10, whichever is earlier, Julie Masow, a Novartis spokeswoman, said.

Kisuk Lee of Harness Dickey, Troy, Mich., told Bloomberg BNA in a March 9 phone interview that the advance of biosimilars will remain uncertain until there are more legal precedents concerning the BPCIA.

Low-Hanging Fruit

Ropka told Bloomberg BNA that she was surprised at the swiftness of the FDA's approval of Zarxio. “The guidance that the FDA gave suggested that there would be an element of caution on its part in its first biosimilars approval. So, for this biosimilar to move from an abbreviated biologic license application in July to a recommendation for approval in January to an approval in March seems pretty fast.”

Ropka said that for the FDA to move as quickly as it did required an almost perfect biosimilar candidate. “And that's what a biosimilar of Neupogen would appear to have been. A Neupogen (filgrastim) biosimilar has been on the market in Europe for six years. Neupogen has been around since 1991, so there's a lot of experience with it. What you really had between the brand name and the European biosimilar was a great big clinical trial. It also helped that filgrastim is a fairly simple protein.”

The FDA and Sandoz also reportedly have discussed bridging studies between the European biosimilar and the planned U.S. biosimilar to bridge the data gap between the European approval and the U.S. approval. “The FDA basically said, show us what data you have and we'll tell you what we still need. FDA said in it guidance to come and speak to the agency in this fashion, and Sandoz did,” Ropka said.

Loots said it's nice to see the biosimilar approval process moving forward five years after the BPCIA was passed. “It's an interesting system that is designed to benefit everyone as long as it works. There's a huge amount of interest out there. As of last October, the FDA received 78 requests and conducted 63 interviews, although that includes an overlap of targets. Last year there were four aBLA submissions and this year there has been one.” He said he believes the low-hanging fruit perspective is the right one to have at this point. “Things could be different for more complex molecules.”

Ropka noted that the FDA's mid-March panel meeting on Celltrion's biosimilar of Remicade, a monoclonal antibody used in cancer treatments, has been delayed.

Lee said, “Other companies are developing biosimilars, and each product will have its own characteristics and its own unique problems. This is a good first step, but it's just a first step.”

BIO Seeks Naming Policy

The FDA's approval of Zarxio was praised by the Generic Pharmaceutical Association, which said it was the beginning of “a new era for cancer patients and the American health care system.” Rep. Frank Pallone (D-N.J.), ranking member of the House Energy and Commerce Committee, said the FDA's approval of Zarxio “show[ed] that the biosimilar approval process is working.”

But Jim Greenwood, president and chief executive officer of the Biotechnology Industry Organization (BIO), expressed concern about the lack of FDA guidance on the naming of biosimilars.

Greenwood said in a statement that BIO has for more than a decade called for an open, transparent and science-based dialogue on biosimilars and continued to support the BPCIA. But, he added, “It is unfortunate that the lack of publicly available naming guidance resulted in FDA's assignment of a ‘placeholder' name for the approved biosimilar.” The FDA's designation of “a placeholder non-proprietary name for this product as ‘filgrastim-sndz' [should] not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilar and other biological products.”

Greenwood added, “We continue to urge the Administration to issue guidance promptly on this crucial matter, as well as on other biosimilar related issues.”

Naming, Pricing Still Issues

As for BIO's concern about the lack of a naming policy, Ropka said, “The brand name [reference product companies] want the biosimilars to have unique names, the biosimilar companies want to use the chemical name, but the brands say biosimilars are not interchangeable. This is still an issue because it didn't get played out with the first biosimilar approval. Sandoz didn't trigger the issue because it gave its biosimilar a proprietary name, and the FDA assigned a place-holder name until its guidance is issued.”

Lee suggested that it is best to wait until the FDA releases its guidance, which it says will be in the “near future.”

Loots raised the question of pricing. “If the price of the biosimilar is 30 percent less than the particular biologic and you're dealing with a $100,000 biologic, $30,000 is a lot of money to be able to save. But if the biosimilar still costs $70,000, it remains to be seen whether this is really a race to the bottom and how well such biosimilars can compete. We really don't know the effect of pricing as a result of changes in manufacturing processes and other issues, and we'll just have to wait and see.”

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