Biosimilars Update: FDA Staff Recommends Approval of First Biosimilar in U.S.; Agency Accepts Third Biosimilar Application For Review

FDA’s “Purple Book,” which lists all licensed biological products, currently has an empty column under the “biosimilar” heading, which would state imitation products deemed “highly similar” next to the listed reference. That may change soon. Tomorrow, the FDA will consider whether the Agency should approve Novartis AG’s copy of Neupogen, Amgen Inc.’s successful injectable biologic used to prevent infection in patients on chemo therapy. FDA staff reviewers recommended approval for the copy on all five of its proposed indications yesterday.

View the FDA Briefing Document in advance of the Oncologic Drugs Advisory Committee Meeting, scheduled for tomorrow, January 7, 2015. 

The inherently complex nature of biologics like Neupogen makes them expensive to develop and impossible to copy in the manner traditionally associated with the approval of generic drugs. Most biologics are produced in living organisms, such as plant or animal cells, whereas small molecule drugs (most pharmaceuticals) are typically manufactured through chemical synthesis. Thus, even creating “similar” biologics is an inherently unpredictable process. 

To aid firms in creating cheaper generic options for biologics–potentially saving the U.S. billions in brand-name alternatives–the Affordable Care Act included an abbreviated approval pathway for products that are demonstrated to be “highly similar” (as opposed to identical) to an FDA-approved biological product. In May, FDA came out with a 17-page draft guidance for companies looking to file what is known as a 351(k) biosimilar application to consider. 

Novartis’s generic submission, for now referred to as “EP2006,” was the first time we got to see how FDA would analyze a biosimilar application. The company is seeking approval for five propose indications (beginning page 6). “Taken together in considering the totality of the evidence,” FDA staff writes, “the data submitted by the Applicant show that EP2006 is highly similar to US-licensed Neupogen and the clinical data have shown that there are no clinically meaningful differences between EP2006 and US-licensed Neupogen suggesting that EP2006 should receive licensure for each of the 5 indications for which Neupogen is currently licensed.” The recommendations are included in a 60-page analysis of various data that Novartis submitted with their application. 

If approved, Novartis’s biosimilar will become the first cleared for sale in the U.S. through the ACA’s accelerated path. The U.S., however, is fairly late to the game. European regulators began approving biosimilar products in 2006 and cleared imitations of Neupogen for sale in 2008. Novartis’s biosimilar is already sold in more than 40 countries outside of the U.S. under the brand name Zarzio. In fact, Novartis already holds more than 50 percent of the world biosimilars market, and is aiming to expand to capture even more shares. 

Amgen could see a fair amount of generic competition coming down the line. In December, Apotex Inc., the largest Canadian-owned pharmaceutical company announced that the FDA had accepted for filing the company’s application for biosimilar of Amgen’s Neulasta, which is the long acting formulation of Neupogen. This is the third biosimilar application FDA has accepted. In July 2013, Novartis submitted its Zarzio application and soon after, on August 11, South Korean biopharmaceutical manufacturer Celltrion announced they would be filing an application for FDA approval for their drug Remsima, its biosimilar version of Jannsen’s Remicade. Remicade is an antibody used to reduce inflammation of Crohn’s disease, rheumatoid arthritis, and psoriasis. 

Amgen is not taking the incoming competition lightly. Last year Amgen filed a lawsuit against Sandoz (the generic division of Novartis) attacking the company for not following the procedures laid out in the Biologics Price Competition and Innovation Act (BPCIA). Amgen argues that Sandoz failed to disclose certain mandatory information after submitting its biosimilar application to FDA. Despite the litigation, according to Bloomberg Amgen is working on biosimilars itself, including an experimental version of Abbvie’s psoriasis drug Humira–the best selling biologic of 2014. 

Click here for the Oncology Drugs Advisory Committee Notice of Meeting. We will be interested in following the outcome of the meeting and expect 2015 to be a big year for biosimilars.