Arthritis is a disease of the joints. Osteoarthritis, which is generally the result of "wear and tear", is a condition in which inflammation of the joints results in pain and degeneration. Rheumatoid arthritis is an autoimmune disease in which the immune system attacks the joints. According to the CDC, over 46 million Americans suffer from arthritic symptoms, and 19 million are physically limited by their condition. The pharmaceutical market for arthritis generated $15.4 billion in revenues in 2008.
The major players in the arthritis drug market include Abbott Laboratories, Johnson & Johnson, Amgen, Roche, and Pfizer. Abbott Laboratories' Humira, which was approved by the FDA in 2003, is both the fastest growing and highest selling drug in the arthritis market, with sales growing 50% from 2007 to 2008 to $4.5 billion.
The arthritis drug market is dominated by biologic drugs, specifically proteins which block tumor necrosis factor (TNF). New legislation to pave a pathway for generic biologics, also known as "follow-on biologics" will affect the arthritis market by potentially enabling entry of generic competition which will lower prices and decrease the overall market size. In addition, there have been concerns that anti-TNF antibodies can lead to cancer in children and adolescents. These factors illustrate the importance of innovation within the arthritis drug market. New drugs under development with novel mechanisms of action have the opportunity to achieve blockbuster sales in this market.
Humira, which Abbot Laboratories' launched in 2003 to treat rheumatoid arthritis, achieved sales of $4.5 billion in 2008, a 50% growth from 2007. Abbott attributes most of this growth to approvals for subsequent indications that Humira has added such as psoriatic arthritis and Crohn's disease. Since Humira is a biologic, there is no clear path of approval for generic medications, protecting the drug from generic competition. However, legislation is currently being proposed around biosimilars that will create such as path.
Humira is a genetically-engineered recombinant protein developed against tumor necrosis factor (TNF). Anti-TNF antibodies represent the largest group of therapies against Rheumatoid arthritis, including the major drugs Remicade, Enbrel, and Rituxan.
Humira can be self-administered through subcutaneous injection, and is recommended to be taken once every two weeks, making it the longest lasting dose on the market.
Johnson & Johnson's Remicade is approved for several indications, including Crohn's disease, psoriatic arthritis, and rheumatoid arthritis. In 2008, Remicade achieved $3.7 billion in sales, a growth of 12.7% over 2007. Like Humira, Remicade is a biologic and is not currently threatened by generics. However, legislation concerning follow-on biologics will affect Remicade in the future.
Remicade (infliximab), like Humira is a recombinant anti-TNF protein. Remicade was approved 3 years earlier than Humira, in 1999,and must be administered intravenously by a physician every 8 weeks, a process that takes around 2 hours.
Amgen's Enbrel, approved in 1998, is the first biologic approved by the FDA to treat rheumatoid arthritis. In 2008, Enbrel achieved $3.6 billion in sales, an growth of 11% over 2007. Enbrel sales increased largely due to an increase in demand from an increased average sale price as well as Amgen's shift to a wholesale distribution model. Like Humira and Remicade, Enbrel is a biologic and is not currently threatened by generics. However, legislation concerning follow-on biologics will affect Enbrel in the future.
Enbrel was the first recombinant anti-TNF protein developed for clinical use. Enbrel can be self-administered by patients via subcutaneous injection, and must be taken twice weekly.
Pfizer's Celebrex was approved by the FDA in 2005 to treat spinal arthritis and in 2006 to treat juvenile rheumatoid arthritis. In 2008, Celebrex achieved $2.49 billion in sales, an increase of 9% from 2007. The major product patent for Celebrex will expire on November of 2013, at which point generic versions of the drug may be produced.
Unlike Humira, Remicade, Enbrel, and Rituxan, Celebrex is a small molecule drug and may be taken orally. Celebrex belongs to the nonsteroidal antiinflammatory drug (NSAID) class of drugs, which includes Vioxx and Bextra as well. NSAIDs work by blocking COX enzymes, which are known to be involved in the painful inflammation associated with arthritis. NSAIDs, however, have been shown to increase the risk of cardiovascular events and gastrointestinal bleeding, and the FDA currently mandates boxed-warnings to be included in the packages of all NSAIDs.
While the FDA did not require Pfizer to recall Celebrex, as it did for Pfizer's Bextra and Merck's Vioxx, Celebrex is currently the subject of litigation from patients who suffered adverse effects from the drug. In the third quarter of 2008, Pfizer settled the remainder of lawsuits pertaining to personal injury from users of Bextra and Celebrex for $745 million. The company claims that this amount will be sufficient to resolve all known U.S. personal injury claims.
Roche acquired the blockbuster cancer drug, Rituxan, in its acquisition of Genentech in 2008. Rituxan, the world's best-selling cancer drug, generated $5.53 billion in revenues in 2008, of which $746 million were obtained from its indication to treat Rheumatoid arthritis. Like Humira, Enbrel, and Remicade, Rituxan is a biologic and is not currently threatened by generics. However, legislation concerning follow-on biologics will affect Rituxan in the future.
Rituxan selectively targets CD20-positive B-cells, and is the first arthritis medication with this mechanism of action. Rituxan is administered intravenously in combination with methotrexate in two doses, separated by two weeks. This treatment must be repeated every 6-9 months. Rituxan is only approved for use when patients have failed treatment by a first-line drug such as Humira, Enbrel, or Remicade.
Merck's Arcoxia achieved $377 million in sales in 2008, a growth of 14.6% from 2007. While Arcoxia is approved for sale in 63 countries throughout the world, it is not approved in the United States. In April of 2007, the FDA voted against the approval of Arcoxia to be used as an arthritis treatment due to a risky safety profile. Like Celebrex, Arcoxia is an NSAID.
Merck had previously run into problems with the blockbuster NSAID, Vioxx, which the FDA forced Merck to recall in 2004. Analysts have touted Arcoxia as a successor to Vioxx for Pfizer. However, the lack of a significant improved safety profile has stood in the way of widespread commercial success for Arcoxia.
|Rank||Market Share||Company||Product||Revenue ($ billion)||Growth|
|2||24%||Johnson & Johnson||Remicade||3.70||18%|
Simponi (Johnson & Johnson and Schering-Plough): Simponi is an anti-TNF antibody in the same class as Humira, Remicade, and Enbrel. Simponi was approved in April 2009 by the FDA for the treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis (alone or with methotrexate), and active ankylosing spondylitis. Simponi may be administered subcutaneously at home once a month, a less frequent dose than either Humira or Enbrel.
Cimzia (UCB SA XOMA): Cimzia, an anti-TNF antibody used to treat Crohn's disease, was approved in May 2009 by the FDA to treat rheumatoid arthritis. Cimzia may be administered subcutaneously at home every 2-4 weeks. Cimzia is approved only in the US and in Switzerland.
Arzerra (Genmab and GlaxoSmithKline): Arzerra (ofatumumab) is an anti B-cell protein in the same class as Rituxan. In July 2009, GlaxoSmithKline and Genmab announced positive Phase III results for Arzerra as a treatment for rheumatoid arthritis.
Over 80% of the arthritis drug market consists of biologic therapies, which are biologically-produced protein drugs. Biologics are far more complex than traditional chemically-synthesized small molecule drugs, and there is no guarantee that a "generic" biologic produced at one plant will mirror the "branded" biologic that it is intended to imitate. This presents a challenge to the FDA for creating a pathway for generic treatments.
The result of this lack of a generic biologics pathway is that approved biologics have existed in the marketplace free of generic competition for decades. However, there is currently legislation being proposed that will create such a pathway, enabling generic competition into the marketplace. While the high cost and complexity of manufacturing a biologic relative to a traditional small molecule drug will keep prices from falling as precipitously as they do when generics enter in small molecule markets, generic biologics will decrease revenues for Humira, Enbrel, Remicade, and Rituxan.
In August of 2009, the FDA sent out an alert requiring all manufacturers of TNF blockers to insert a warning into their drug packages warning of an increased risk of lymphoma and other malignancies in children taking the medications. This report was based off of an assessment of post-marketing data from anti-TNF therapies that indicated an increased risk of cancer in children and adolescents. This risk associated with usage of anti-TNF therapies such as Humira, Remicade, and Enbrel may decrease the market for these drugs and open space for competition from non-anti-TNF medicines such as Rituxan or Celebrex.