Amgen will not launch its biosimilar of AbbVie’s Humira in U.S. until 2023

One cannot watch a program on cable television without likely catching a commercial for Humira with its iconic mauve ribbon branding. AbbVie’s blockbuster drug, Humira (adalimumab) was the best selling drug of 2016, with net sales of over $14 billion, a 15% increase from 2015. While it was not the first approved TNFα-inhibitor, Humira was the first approved fully human monoclonal antibody in its class. The brand name Humira stands for “human monoclonal antibody in rheumatoid arthritis”. Remicade (infliximab), a mouse-human chimeric antibody, was the first approved TNFα-inhibitor and Enbrel (etanercept), a fusion protein, was the second. In 2001, pivotal results from ARMADA, AbbVie’s phase III double-blind, placebo-controlled trial involving 271 patients, showed a 50% improvement in ACR score (or, reductively, a 50% joint improvement) using Humira. Since then, Humira has become a staple in the armamentariums of rheumatologists, dermatologists, and gastroenterologists. After its original approval in RA in 2002, the timeline for indication approvals follows:

Humira-approvals-by-year

  1. Rheumatoid Arthritis (2002)
  2. Psoriatic Arthritis (2005)
  3. Plaque Psoriasis (2008)
  4. Adult Crohn’s Disease (2008)
  5. Juvenile Idiopathic Arthritis (2008)
    • Orphan
  6. Ankylosing Spondylitis (2008)
  7. Ulcerative Colitis (2012)
  8. Uveitis (2014)
    • Orphan
  9. Pediatric Crohn’s Disease (2014)
    • Orphan
  10. Hidradenitis Suppurativa (2015)
    • Orphan

In the United States, drugs qualify for orphan status if they treat a disease affecting less than 200,000 patients, thus meriting an additional 7 years of market exclusivity. With 10 indications and a few orphan designations to boot, it’s not difficult to see why Humira is one of the best selling drugs in the world. And, as of September 28, in a major win for AbbVie, their legal team successfully deterred biosimilar competitors until 2023 in the U.S. and until 2018 in Europe. Indeed, Amgen’s Amjevita was approved September 2016 in the U.S., yet it will not be commercially available any time soon.

Biosimilars 101

Most are aware of generics because most of the time, we can acquire generic drugs for a fraction of the cost of the brand-name drug. Biosimilars are essentially “the generic” of a biologic type of drug, but with a few important caveats as the analogy is imperfect.

Until the 1980s, all drugs were simple chemical entities. Take for example, aspirin, which has a very simple formula, C9H8O4. Aspirin is comprised solely of 9 carbon, 8 hydrogen, and 4 oxygen atoms. Because of its simplicity, every single time researchers synthesize aspirin, it is exactly the same with no variation. Humira is an antibody with a molecular weight 800X greater than aspirin. Biologic antibodies cannot be chemically synthesized like aspirin and the technological requirement of a cell line to produce an antibody just happens to be inherently variable.

While the U.S. pathway for the approval of generics (The Hatch-Waxmen Act of 1983) has shown considerable success in decreasing the price of drugs, the pathway for the approval of biologics (The Biologic Price Competition and Innovation Act of 2010) was likewise paved for prospective cost savings, yet requires an additional layer of scrutiny due to the inevitable variability of these cell-generated biologics. As the technology to produce antibodies like Humira is nontrivial and far more complex than the technology to produce a chemical entity like aspirin, AbbVie successfully delayed biosimilar competitors far past their market exclusivity date of 2016 to 2023 due to the dozens of formulation, manufacturing, and methods patents. As the goal of the biosimilars pathway was to facilitate cost savings, what does that mean for patients?

Cost savings of biosimilars

No one knows—no, quite literally, at least for the U.S., no one knows. Sure, there are U.S. cost savings projections in the ballpark of 15-30%. Indeed, Pfizer’s infliximab biosimilar, Inflectra, was recently introduced at a 15% wholesale acquisition cost (WAC) discount. And sure, Pharma manufacturers, insurance providers, and pharmacy benefit managers (PBMs) alike are touting in a very public relations-sensitive fashion the impending cost savings of biosimilars. The U.S. healthcare market herein is specifically differentiated as it quite unlike that of Europe, which may already be a decade ahead of the U.S. in its implementation of biosimilars. Furthermore, Inflectra is discussed not in terms of a general cost savings, but specifically a WAC discount, because the actual, effective cost savings to patients remains nebulous. Perhaps you have noticed that the American healthcare system is like a Rube Goldberg machine, where everything is intertwined, the outcome is non transparent, and Rube Goldberg, or the inventor, has left the building. There is nothing but speculation about the cost savings of biosimilars, yet the one trend emerging is the stark contrast between the U.S. and European healthcare systems.

Imagine the outcry and resistance if the United States government fully funded and mandated patients successful on Humira to switch to a trial biosimilar. Well, the Norwegian government successfully executed such an experiment/trial between 2014 and 2015 using an infliximab biosimilar, Remsima (the European counterpart to Inflectra). This aptly named NOR-SWITCH trial involving 482 patients showed that switching from infliximab originator to the biosimilar was non-inferior. By the close of the study year, in 2015, Remsima hit 80% market share at a steep 69% discount. While Inflectra only became commercially available at the close of 2016, penetration is expected to hit a nominal 10% market share in the U.S. at a 15% discount. Notably, as of August 2017, the European Medicines Agency has approved 35 biosimilars, whereas the Food and Drug Administration has only approved 6, which almost seems akin to the ratio of available cheese varietals. Aside from the ever-present concern of emergent efficacy or safety signals, it remains to be seen whether the U.S. healthcare system and all of its tentacles of complexity can pivot biosimilars into a meaningful cost savings to patients as the only thing we now for certain is that the the American leviathan in its current state has proven it is far less nimble than its European counterparts. For better or worse.

cheese

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My Lithe

Health technology and personalized medicine

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