The trade name of Infliximab is Remicade. This biologic drug is used for the treatment of Crohn’s disease, ulcerative colitis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis and also used off-label outside its FDA approval for Behcet’s disease and other conditions. Remicade is the first approved TNF-alpha inhibitor available in the U.S. that pharmaceutical supplier for hospitals distributed it.
Infliximab is called a chimeric monoclonal antibody drug; at first, it was developed in mice as a mouse antibody. Since humans have immune reactions to mouse proteins, so similar human antibody domains replace the mouse common domains. They are monoclonal antibodies with identical structures and affinities to the target and since they are a combination of mouse and human antibody amino acid sequences, they are called a “chimeric monoclonal antibody”.
- In 2002: the FDA approved it as the first TNF-alpha inhibitor for maintenance therapy in patients with moderate to severe Crohn’s disease. It also became the first TNF-alpha inhibitor indicated in the U.S. to improve physical function in patients with moderate to severe RA who have had an inadequate response to methotrexate
- In 2003, It was approved in the EU for the treatment of ankylosing spondylitis in patients with severe axial symptoms, elevated serological markers of inflammatory activity and also with an inadequate response to conventional therapy.
- In October 2004, Remicade was approved as the first TNF-alpha inhibitor for the treatment of active and progressive psoriatic arthritis in patients who have responded inadequately to anti-rheumatic drug therapy.
- In September 2005, Remicade was approved by the FDA as the first and the only biologic drug for use in adults with moderately to severely active UC who have had an inadequate response to conventional therapy. It was approved by EU in 2006.
- In 2006: REMICADE became the first and only biologic indicated to reduce signs and symptoms and induce and maintain clinical remission in pediatric patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy.
- Moderate to severe Crohn’s disease who have had an inadequate response to conventional therapy.
- Moderate to severe Ulcerative Colitis who have had an inadequate response to conventional therapy.
- Moderate to severe rheumatoid arthritis (RA) in combination with methotrexate
- Active ankylosing spondylitis
- Psoriatic Arthritis
- Moderate to severe chronic plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.
Tumor Necrosis Factor alpha (TNF alpha) is a substance made by cells of the body that has an important role in promoting inflammation. Biological activities attributed to TNFα include: induction of pro-inflammatory cytokines such as interleukins (IL) 1 and 6, enhancement of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, induction of acute phase reactants and other liver proteins, as well as tissue degrading enzymes produced by synoviocytes and/or chondrocytes. The action of TNF-alpha should be blocked for reducing the signs and symptoms of inflammation
In the US market, there are currently two biosimilars of infliximab:
- Inflectra, the first biosimilar drug product approved in 2016,
- Ixifi, second biosimilar product approved in 2017 (Pfizer).
In Europe market, two biosimilar versions were submitted for approval in 2013 :
- Inflectra (Hospira ),
- Remsima (Celltrion); it obtained marketing authorization approval from 27 EU countries and 3 European Economic Area countries by 2013.
A new biosimilar version of infliximab was approved in India under the brand name “Infimab” and trail name BOW015. It has been developed by Epirus Biopharmaceuticals.
In April 2017, the US FDA approved Renflexis (infliximab-abda) as the other biosimilar developed by Samsung Bioepsis Co., Ltd.’s.
Another biosimilar under the name Flixabi (Biogen) was approved in Germany, the UK, and the Netherlands.
Centocor, Inc., Schering-Plough Corporation, and Mitsubishi Tanabe Pharma Corporation, some of the pharmaceutical supply chains for hospitals announced REMICADE® (infliximab) as the leading anti-tumor necrosis factor (TNF)-alpha therapy worldwide that around one million patients have been treated by using it.
The U.S. Food and Drug Administration (FDA) approved Remicade in 1998 as the first anti-TNF-alpha treatment that was indicated for the treatment of acute moderate to severe Crohn’s disease and then rheumatoid arthritis.
Its use in a wide variety of diseases of the immune system has been studied in more than 37 clinical trials and finally, it gained its approval to be used in 88 countries.
Companies like Janssen Biotech, Inc. (formerly Centocor Biotech, Inc.) in the USA, Mitsubishi Tanabe Pharma in Japan, Xian Janssen in China, and Schering-Plough (now part of Merck & Co) elsewhere have marketed Remicade.
According to the report of Decision Resources, the TNF-alpha inhibitors infliximab (Janssen Biotech/Merck/Mitsubishi Tanabe’s Remicade) and adalimumab (Abbott/Eisai’s Humira) dominated the Crohn’s disease (CD) market in 2011; they have captured more than three-quarters of market share in the United States, France, Germany, Italy, Spain, the United Kingdom, and Japan.
Sales of Remicade and Humira was a peak of $3.7 billion in 2016 but it has started to decline in 2017 due in part to the increasing uptake of biosimilar versions of these TNF-alpha inhibitors. According to the estimations, sales of biosimilar infliximab and adalimumab will account for 27 percent of combined infliximab and adalimumab molecule sales in 2021.
The overall Crohn’s disease market will increase from approximately $3.8 billion in 2011 to $5.6 billion in 2021. This growth shows the shifting competitive dynamics as market growth from emerging agents outpaces the decline in sales of older established agents that will face increasing generics erosion and declining use.
In the market, there are three injectable drugs that block TNF alpha: Adalimumab (Humira) and Etanercept (Enbrel) and Infliximab. Infliximab starts to take effect within 48 hours for some patients, while others may have to wait several weeks.
Biosimilar infliximab has been available in most countries in Europe since February 2015 but it has not captured a large share of the market as Celltrion and other biosimilar developers had anticipated. The problem is not its price; the main reason is that infliximab is not the preferred therapy for most indications it has been approved for.
For example, for treating rheumatoid arthritis, infliximab is often third-line TNF-alpha inhibitor following Etanercept and Adalimumab. The same is also true about treating of Spondyloarthritis (SPA) and psoriasis, where infliximab’s market share falls behind other anti-TNF-alpha biologics.
In the inflammatory bowel diseases specifically UC, infliximab has the highest market share among the biologic but even in this case both clinicians and patients often prefer the alternatives, be it Adalimumab’s subcutaneous formulation and ease of administration, or the gut-specific Vedolizumab. In fact, it is anticipated that Adalimumab and perhaps Vedolizumab gain market share over infliximab during the next 10 years.
Remicade price is about $750 to $915. Dano Health as one of the pharmaceutical wholesalers for hospitals can provide this drug for hospitals and clinics.