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Global Top 10 Best-selling Drugs

July 05, 2018 By W&D

This article summarizes and introduces the global top 10 best-selling drugs, to present the readers an impression thereon.

Global Top 10 Best-selling Drugs

1.    Humira

AbbVie’s Humira topped the list upon USD 18.4 billion sales in 2017, which were far higher than Revlimid that ranked the second with USD 8.1 billion sales. Humira is predicted to exceed USD 20 billion sales in 2018, to become the first drug exceeding such amount in pharmaceutical history. See the following table for details of the drug:

Trade name

Humira

Generic name

Adalimumab

Company

AbbVie

Structure

A human monoclonal tumor necrosis factor (TNF) α antibody, a dimer formed by connecting human monoclonal D2E7 heavy chain and light chain via disulfide bond

Mechanism of action

Adalimumab binds specifically to TNF-α and blocks its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface TNF-expressing cells in vitro in the presence of complement. Adalimumab does not bind or inactivate lymphotoxin (TNF-β). Adalimumab also modulates biological responses that are induced or regulated by TNF, including changes in the levels of adhesion molecules responsible for leukocyte migration

Therapeutic field

Clinically used for rheumatoid arthritis and ankylosing spondylitis

 

2.    Revlimid

The drug that ranked the second is Revlimid from Celgene Corporation, with 2017 sales of USD 8.1 billion; this drug is a small molecule chemical drug unlike Humira, with details as shown in the following table:

Trade name

Revlimid

Generic name

Lenalidomide

Company

Celgene Corporation

Structure

Mechanism of action

The definite mechanism of action is not quite clear at present; its actions may be in many aspects, mainly the direct cytotoxic action and indirect immunization

Therapeutic field

Clinically used in combination with dexamethasone, to treat adult patients with multiple myeloma who received at least one prior therapy

3.    Enbrel

The 2017 sales of this drug were USD 8 billion and ranked the third. The drug is a bio-macromolecular drug with the therapeutic field similar to Humira that ranked the first. The details are as shown in the following table:

Trade name

Enbrel

Generic name

Etanercept

Company

Amgen/Pfizer/Takeda

Structure

Human tumor necrosis factor receptor p75 Fc-fusion protein produced using Chinese hamster ovary (CHO) mammalian cell expression system; a dimer formed by fusing the extracellular ligand binding domain of human tumor necrosis factor receptor 2 (TNFR2/p75) to the Fc fragment of human IgG1.

Mechanism of action

Etanercept is a competitive inhibitor of TNF binding to its cell surface receptors and thereby prevents TNF-mediated cellular responses by rendering TNF biologically inactive. Etanercept may also modulate biologic responses controlled by additional downstream molecules (e.g., cytokines, adhesion molecules, or proteinases) that are induced or regulated by TNF.

Therapeutic field

Rheumatoid arthritis, ankylosing spondylitis

4.    Remicade

This drug is also a bio-macromolecular drug, with 2017 sales of USD 7.7 billion that ranked the fourth. The details are as shown in the following table:

Trade name

Remicade

Generic name

Infliximab

Company

J & J/MSD/Mitsubishi Tanabe

Structure

Chimeric human-murine monoclonal antibody

Mechanism of action

Infliximab is a chimeric human-murine monoclonal antibody that neutralizes the biological activity of TNF by binding with high affinity to the soluble and transmembrane forms of TNF-α and inhibits binding of TNF-α with its receptors. Infliximab does not neutralize TNF-β (lymphotoxin α), a related cytokine that utilizes the same receptors' as TNF-α.

Therapeutic field

Rheumatoid arthritis, Crohn's disease, Crohn's disease with fistulas, ankylosing spondylitis, psoriasis

5.    Herceptin

Roche’s Herceptin ranked the fifth with USD 7.1 billion sales, which is also a bio-macromolecular drug, with information as follows:

Trade name

Herceptin

Generic name

Trastuzumab

Company

Roche

Structure

Anti-HER2 monoclonal antibody

Mechanism of action

Trastuzumab selectively binds with P185 glycoprotein. It is an anti-HER2 monoclonal antibody that inhibits the growth of HER2-positive cancer cells, with significant clinical efficacy. After intravenous injection of trastuzumab, the antibody targets (specifically acts on) HER2-overexpressing breast cancer cells, to inhibit the interaction of the growth factor and cancer cell.

Therapeutic field

Metastatic breast cancer, adjuvant therapy of breast cancer, metastatic gastric cancer

6.    Avastin

This drug is also a blockbuster of Roche and bio-macromolecular drug, with sales next to those of Herceptin to reach USD 6.8 billion. The drug information is as follows:

Trade name

Avastin

Generic name

Bevacizumab

Company

Roche

Structure

Humanized anti-VEGF monoclonal antibody

Mechanism of action

Bevacizumab specifically binds vascular endothelial growth factor (VEGF) and prevents the interaction of VEGF to its receptors. It has multiple actions on tumor vasculature: regress existing tumor vasculature, to cut off the oxygen and other nutrients required for tumor cell growth;

It normalizes the tumor vasculature that survives, decreases intra-tumoral pressure, which subsequently leads to increased delivery of chemotherapy to the tumor cells, to improve the chemotherapy effect; it inhibits tumor angiogenesis, to continuously inhibit tumor cell growth and metastasis.

Therapeutic field

Metastatic colorectal cancer: bevacizumab in combination with 5-fluorouracil-based chemotherapy to treat patients with metastatic colorectal cancer

7.    Xarelto

Bayer’s Xarelto, one of the few small molecule drugs in Top 10, ranked the seventh upon USD 6.2 billion sales, with information as follows:

Trade name

Xarelto

Generic name

Rivaroxaban

Company

Bayer

Structure

Mechanism of action

Rivaroxaban is a Factor Xa inhibitor with bioavailability, selectively blocks the active site of Factor Xa, and does not require a cofactor (such as Anti-thrombin III) for activity. Activation of Factor X to Factor Xa (FXa) via the intrinsic and extrinsic pathway plays a central role in the cascade of blood coagulation.

Therapeutic field

Prevention of venous thromboembolism (VTE) in adult patients who have undergone selective hip or knee replacements

Treatment of deep vein thrombosis (DVT) in adults and reduction in the risk of recurrent DVT and pulmonary embolism (PE) after acute DVT

Reduction of risks of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation and at least one additional risk factor for stroke.

 

8.    Mabthera

This drug is another blockbuster of Roche with sales of USD 5.9 billion, and is also a bio-macromolecular monoclonal antibody drug, with information as follows:

Trade name

Mabthera

Generic name

Rituximab

Company

Roche

Structure

Chimeric murine/human monoclonal antibody

Mechanism of action

Specifically binding to transmembrane antigen CD20

Therapeutic field

Relapsed/resistant follicle center lymphoma

9.    Eylea

Bayer’s bio-macromolecular drug Eylea ranked the ninth upon USD 5.8 billion sales, which is an ophthalmic drug with details as follows:

Trade name

Eylea

Generic name

Aflibercept

Company

Regeneron/Bayer

Structure

Aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa. Aflibercept is produced in recombinant Chinese hamster ovary (CHO) cells.

Mechanism of action

Aflibercept binds VEGF-A and PlGF, and thereby can inhibit the binding and activation of these cognate VEGF receptors.

Therapeutic field

Patients with neovascular (wet) age-related macular degeneration (AMD)

 

10.  Opdivo

Sales of this drug, the first PD-1 targeted drug marketed in China, reached USD 5.7 billion, which is used to treat advanced squamous non-small cell lung cancer (NSCLC), with details as follows:

Trade name

Opdivo

Generic name

Nivolumab

Company

BMS/Ono Pharmaceutical

Structure

Monoclonal antibody

Mechanism of action

It releases tumor cells’ inhibition of the immune system by inhibiting PD-1/PD-L1 signaling pathway, and the immune system is activated to clear the tumor cells, therefore, it is called tumor immunotherapy

Therapeutic field

Epidermal growth factor receptor (EGFR) mutation-negative and anaplastic lymphoma kinase (ALK)-negative adult patients who have locally advanced or metastatic NSCLC with progression on or intolerance to prior platinum-based chemotherapy

From the above content, we can see that the total sales of the top 10 best-selling drugs reached USD 79.7 billion, wherein, the bio-macromolecular drugs were in the majority, and chemical small molecule drugs only occupied 2 places, showing the strong development momentum of bio-macromolecular drugs, and the unique advantages thereof in relevant therapeutic fields.

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