Enbrel (Etanercept) in Dano Health view
Enbrel is the trade name of Etanercept. It is the first anti-tumor necrosis factor (TNF) agent to be approved for the treatment of Rheumatoid Arthritis (RA).
This protein drug is used alone or in combination with an immunosuppressant such as Methotrexate to treat certain types of arthritis like rheumatoid, psoriatic, juvenile idiopathic, and ankylosing spondylitis. Some brands of this drug are also used to treat a skin condition called psoriasis.
In the 1990s, Bruce and Beutler were the first researchers who studied on Etanercept. They synthesized the prototypic fusion protein and found that they are highly active and unusually stable as a modality for blockade of TNF in vivo. They also patented the protein, selling all rights to its use to Immunex, a biotechnology company that was acquired by Amgen in 2002.
ENBREL was approved for treating
- moderate-to-severe rheumatoid arthritis in 1998.
- moderate-to-severe poly-articular juvenile idiopathic arthritis in 1999.
- psoriatic arthritis in 2002
- patients with ankylosing spondylitis in 2003
- moderate-to-severe plaque psoriasis in adults in 2004
Enbrel is used for treating
- Patients with moderately-to-severely active rheumatoid arthritis (RA). It can be initiated in combination with methotrexate (MTX) or used alone.
- Patients aged 2 years or older with moderately-to-severely active polyarticular juvenile idiopathic arthritis
- Patients with psoriatic arthritis. It can be used with or without methotrexate.
- Patients with active ankylosing spondylitis.
- 4 years or older patients with chronic moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
TNF (Tumor necrosis factor) is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. There are increased levels of TNF in tissues and fluids of those with Rheumatoid Arthritis (RA), Polyarticular Juvenile Idiopathic Arthritis (JIA), Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS).
There are two type of receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75). The biological activity of TNF will differ depends on binding to either cell surface receptor (p75 or p55).
Etanercept is a dimeric soluble form of the p75 TNF receptor that can bind to two TNF molecules and decrease their role in disorders involving excess inflammation in humans and other animals including autoimmune diseases such as ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and also in a variety of other disorders mediated by excess TNFα.
Anti TNF agent’s molecular characteristics
The pharmacological class of TNF alpha inhibitors is Etanercept (Enbrel), Infliximab (Remicade) and Adalimumab (HUMIRA). Mechanisms of action and therapeutic uses (rheumatologic diseases, bowel inflammatory disease, and psoriasis) of these drugs are the same.
Etanercept (Enbrel) was the first approved TNF alpha blocker in May 1998. Then came infliximab (Remicade) in November 1999 and adalimumab (HUMIRA) in December 2002.
The latest information on the FDA approved uses of three selected TNF alpha blockers are shown in the following chart.
|Etanercept (Enbrel)||Infliximab (Remicade)||Adalimumab (Humira)|
|Rheumatoid Arthritis (RA)||Yes||Yes||Yes|
|Polyarticular Juvenile Idiopathic Arthritis (JIA)||Yes||No||Yes|
|Ankylosing Spondylitis (AS)||Yes||Yes||Yes|
In 2011, Cipla (OTC: CPLFY), a major drug company in India, produced an Enbrel copy at a 30 percent discount compared to Enbrel price in India; Etacept is the name of this new product which resembles the name of Enbrel’s active ingredient, Etanercept.
Amgen (NASDAQ: AMGN) and Pfizer (NYSE: PFE), main Enbrel wholesalers, co-promoted Enbrel; it is one of the most successful drugs in history. Amgen sells the drug in the U.S. and Canada, Pfizer sells it to the rest of the world. Enbrel was the world’s second best-selling drug. Earning of Amgen from Enbrel’s sales is $4.2 billion in the US and Canada and $3.7 billion for Pfizer from sales outside the U.S. and Canada. Pfizer also received $1.5 billion from Amgen as its share of the profits from the sales in the U.S. and Canada in 2012. Pfizer partners with Takeda in Japan. Pfizer grossed about $1 billion from this partnership last year.
Even after 20 years on the market, sales of Enbrel have increased for Amgen by 15 percent and for Pfizer by 2 percent from the previous year. So Enbrel’s success is remarkable.
In 2011 Amgen got a new U.S. patent for Enbrel that will last until 2028. Some biosimilar manufacturers try to challenge this patent or work around it, but this patent makes Amgen’s management feel reasonably safe inside the U.S. market while that may not be the case outside the U.S. and Canada for Pfizer.
Dano Health as a clinical trial product seller can provide Avastin for the companies who want to search on it.
India is a big market for Enbrel. Rheumatoid arthritis affects a huge number of the Indian population (around 0.7 percent of the Indian people above the age of 16 years). For treatment, 60 percent manage RA with branded generics, such as a combination of methotrexate and Arava, while the balance needs biologics such as Enbrel and Johnson & Johnson’) Remicade which also sells in India. Now, just 5 percent of RA patients who need biologics are taking them so there is potential for growth. But certainly, Pfizer will be the loser if Cipla is able to convince the doctors to prescribe its medication.
ENBREL was first approved for patients with moderate to severe rheumatoid arthritis and then got four other approvals by the FDA (moderate-to-severe poly-articular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, moderate-to-severe plaque psoriasis in adults), after all of this approval its revenues go up.
ENBREL ‘s age and success have made it a marked drug with biosimilar developers placing it at the top of their lists. Turkish pharmaceutical exporter alongside other Enbrel wholesalers and exporters are all so eager about this market. Enbrel is being on the market for over 18 years and it still holds “general subject matter” patents in the U.S. So, Amgen is conducting two phase 3 studies for Enbrel as monotherapy for treating psoriatic arthritis and rheumatoid arthritis remission to further expand the labels of the drug.