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FDA Biosimilar Approval of Inflectra Viewed as a Milestone Advance

Apr 06, 2016 9:59 am

On February 9th, the Food and Drug Administration (FDA) Arthritis Advisory Committee voted 21-3 in favor of approving the infliximab biosimilar, CT-P13/Inflectra, for use in all of infliximab's indications.  A mere 8 weeks later, the FDA has approved Inflectra (infliximab-dyyb), the first biosimilar for use in inflammatory disorders such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis and juvenile idiopathic arthritis.   

“Biosimilars can provide access to important treatment options for patients who need them,” said Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research. “Patients and the health care community can be confident that biosimilar products are high quality and meet the agency’s rigorous scientific standards.” 

Many believe the new biosimilar will initially be used for new biologic starts and not be substituted, or be interchangible, for current Remicade use. 

"It is important to note that the FDA has not approved Celltrion's infliximab-dyyb as being interchangeable with Remicade," said J&J's Chief Biotechnology Officer Jay Siegel in a statement. "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." 

Inflectra is made by South Korea's Celltrion Inc in partnership with Pfizer Inc's Hospira unit, and is the second biosimilar approved in the USA.  The discounted price of the infliximab-dyyb has not yet been announced but is expected to be 20-30% lower than the current price of Remicade (infliximab) in the the U.S. market.

Remicade generated annual worldwide sales of $6.5 billion in 2015. Of that, $4.5 billion were in the United States. Merck & Co sells Remicade in Europe. Celltrion sells the biosimilar overseas under the brand Remsima. Remsima was approved by European regulators in 2013 and began sales in Europe's largest countries in February 2015, where the initial discounts have been as much as 70% lower than market prices all infliximab revenues by 2020.  Also in the mix is another infliximab biosimilar, Flixabi (from Samsung Bioepis and Biogen), that was recently endorsed by the EMA for use in Europe. 

The package insert for Inflectra is available.  Dosing will be the same as Remicade. The drug will come as100 mg of lyophilized infliximab-dyyb in a 20 mL vials for intravenous infusion. It will have the same Boxed Warnings (increased risk of serious infections, tuberculosis, lymphoma and other malignancies), contraindications (doses >5 mg/kg in severe heart failure) and other warnings and precautions side effects (liver injury, blood problems, lupus-like syndrome, psoriasis, demyelinating disorders) listed for Remicade. 

The first FDA-approved biosimilar, Zarxio, modeled after Neupogen, was approved in 2015.  With nearly a year in the market, it is unknown what its impact will be.  Although Zarxio could be one of several factors that may decrease Neupogen sales by 5-10% in the next year, it remains to be seen if the introduction of the biosimilar will expand the market overall.  

Biosimilars are touted as generic biosimilars, designed to deliver the same efficacy and safety at a substantially reduced priced.  Presumably, this will result in greater access for more patients.  It will be interesting to see if the influx of biosimilars will expand the market size overall.  More biosimilars and more manufacturers should promote competition, advertising, and education, and holds the promise of wider use and less cost. 

To date there have been no significant issues or concerns in biosimilar approvals with regard to drug safety or immunogenicity. The current uncertainties surrounding biosimilars involve the issues of price negotiation, extrapolation and interchangibility.  Approval of Inflectra comes without language or data that would allow forced change from current Remicade use to substituted Inflectra.  There has been limited experience with interchangibility in the PLANETAS study suggesting this is plausible and safe. 

This FDA approval heralds a new era of biosimilar introduction and use that will markedly affect the care of many with RA, JIA, psoriasis, psoriatic arthritis, anklylosing spondylitis and IBD.  The short term efficacy and saftey of CT-P13 (infliximab-dyyb) has been established.  There is no reported plan for a REMS program to study its longer term effects and safety.

The author has received compensation as an advisor or consultant on this subject

Rheumatologists’ Comments

Harry Gewanter

| Apr 06, 2016 1:24 pm

Jack, I disagree with the use of the term "generic biosimiliars" as I consider it a misnomer. Since one cannot exactly duplicate a biologic medication and therefore cannot make an exact copy, the resulting medication is a "biosimilar". A generic medication is an exact copy of a chemical medication. Linking the two terms is both incorrect and potentially creates even more confusion from the implications. There should not be any differences with generics; we know there are differences with biosimilars. The amount of education necessary for both patients and providers about biosimilars is YUUGGGE and I believe we need to limit any potential implications that biosimilars are equivalent to generics whenever possible. But, as Dennis Miller used to say, "That's just my opinion; I could be wrong." Harry L Gewanter, MD, FAAP, FACR Richmond, VA US
Harry, your sage comments are spot-on correct. While the man on the street may think of these as generic like - they are not. There will be a steep learning curve to their use and acceptance. Your comments should be the beginning of a "Fact Sheet" the ACR or RheumNow can draw up to explain what a biosimilar is. Thanks for keeping me straight!

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