Orphan drugs refer to drugs used to prevent, treat, and diagnose rare diseases. Rare diseases are a general term for diseases with extremely low incidence, also known as “orphan disease.” According to the definition of WHO, a disease with a total population of 0.65 ‰ to 1 can be defined as a rare disease. However, countries around the world have certain differences in the criteria for identifying rare diseases according to the specific conditions of their own countries.
It is estimated that as many as 7,000 diseases have been defined as rare diseases, of which only about 400 rare diseases have been approved. The total number of rare patients worldwide has reached 300 million.
According to a report released by Evaluate Pharma, a pharmaceutical market research organization, in 2017, the global orphan drug market was US$124 billion, an increase of 8.6% over the previous year; in the next 5 years (2017-2022), It will grow at a compound annual growth rate of 11.1%, reaching $209 billion by 2022, and its share of the prescription drug market will exceed 20% for the first time, reaching 21.4%.
At present, Novartis is far ahead in the orphan drug market with a market share of 11.3%, followed by Roche (8.8%), New Base (8.0%) and Bristol-Myers Squibb (5.8%). In terms of price, Ravicti, a treatment for urea cycle disorders (UCDs) of Horizan Pharma, ranked first with $790,000. It is worth mentioning that UniQure’s gene therapy Glybera was once the world’s most expensive orphan drug, priced at $ 1.21 million, but the drug has been delisted due to poor market performance (detailed schedule).
In recent days, Igeahub, a medical consulting company, released the list of “Top 10 Best Orphan Drugs in 2018”. According to sales, in 2017, the total sales of TOP10 orphan drugs totaled 29.066 billion US dollars. 23.44% of the orphan drug market, these 10 drugs come from 8 companies, including Bristol-Myers Squibb (BMS) and New Base each, Roche, Novartis, Merck, Aibowei, Vertex, Alexion each have one.
Here are the sales of each drug on the Igeahub list.
Development company: Roche
Global sales in 2017: 7.41 billion US Dollar
Rituxan is an anti-CD20 monoclonal antibody drug with active pharmaceutical ingredient rituximab, a human-mouse chimeric monoclonal antibody that binds to CD20 antigen on abnormal B lymphocytes and is dependent on complement. Cytotoxicity and antibody-dependent cytotoxicity trigger an immune response to B cell lysis, killing tumor cells or B lymphocytes. Indications for this drug include non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatous vasculitis, and microscopic polyangiitis.
Development Company: New Base
Global Sales in 2017: 69.74 Billion US Dollars
Revlimid is an immunomodulator with lenalidomide (lenalidomide), a new generation derivative of thalidomide, no teratogenic toxicity, and efficacy compared to Shali The amine is 100 times stronger and has immunomodulatory, anti-angiogenic and anti-tumor properties. The currently approved indications include multiple myeloma, myelodysplastic syndrome, and mantle cell lymphoma.
Development company: BMS
Global sales in 2017: 3.774 billion US Dollar
Opdivo is a PD-1 tumor immunotherapy with the active drug component nivolumab, a monoclonal antibody that targets the negative immunoregulatory receptor PD-1 on the surface of activated T cells. It inhibits its interaction with the tumor surface ligand PD-L1 or PD-L2, thereby releasing the immune potential of activated T cells, preventing the immune escape of tumors, and restoring the body’s anti-tumor immune response. Opdivo has been approved for the treatment of many types of cancer, including: non-small cell lung cancer, melanoma, renal cell carcinoma, head and neck squamous cell carcinoma, liver cancer, bladder cancer, colorectal cancer, Hodgkin’s lymphoma.
Development company: Alexion
Global sales in 2017: 2.843 billion US Dollar
Soliris is a pioneering complement inhibitor with an active pharmaceutical ingredient eculizumab, a monoclonal antibody that specifically binds complement protein C5 with high affinity, inhibiting its cleavage to C5a and C5b, and Prevent the formation of the terminal complement complex C5b-9. The indications that Soliris has approved include: paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor antibody-positive systemic myasthenia gravis (gMG). This drug inhibits terminal complement-mediated endovascular hemolysis in PNH patients and inhibits complement-mediated thrombotic microangiopathy in aHUS patients. The exact mechanism of therapeutic effects in gMG patients is unclear and may involve nerves. The deposition of the terminal complement complex C5b-9 is reduced at the muscle junction.
Development company: Novartis
Global sales in 2017: 1.739 billion US Dollar
Tasigna is a BCR-ABL tyrosine kinase inhibitor with active pharmaceutical ingredient nilotinib, which inhibits the production of cancer cells containing abnormal chromosomes by targeting Bcr-Abl kinase. . The Bcr-Abl protein is produced by cells containing abnormal Philadelphia chromosomes, which are considered to be an important factor in the excessive proliferation of oncogenic leukocytes in patients with chronic myeloid leukemia (CML). At present, the indication that the drug has been approved is Philadelphia chromosome positive CML.
Development Company: Abbott
Global Sales in 2017: $1.58 billion
Imbruvica is a Bruton’s tyrosine kinase inhibitor with an active pharmaceutical ingredient of ibrutinib, which exerts anticancer effects by inhibiting BTK required for tumor cell replication and metastasis. A signaling pathway that mediates the uncontrolled proliferation and spread of malignant B cells, helping to kill and reduce the number of cancer cells and delay the progression of cancer. At present, the approved indications for the drug include non-Hodgkin’s lymphoma, mantle cell lymphoma, Waldenstrom macroglobulinemia, marginal zone lymphoma, and chronic graft-versus-host disease.
Development Company: Merck East
Global Sales in 2017: 1.402 billion US Dollar
Keytruda is a PD-1 tumor immunotherapy with the active pharmaceutical ingredient pembrolizumab, which has the same mechanism of action as Opdivo. Keytruda has been approved for the treatment of many types of cancer, including non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, Hodgkin’s lymphoma, microsatellite, highly unstable cancer, bladder cancer, and gastric cancer.
Development Company: New Base
Global Sales in 2017: 13.11 Billion Dollars
Pomalyst is an immunomodulator with active ingredient pomalidomide, a third-generation thalidomide analog that is more potent than thalidomide and second-generation lenalidomide. It is higher in toxicity and less in toxicity, and has antitumor activity, immunomodulatory activity, and angiogenesis inhibitory activity. The approved indication is multiple myeloma.
Development company: BMS
Global sales in 2017: 1.053 billion US Dollar
Yervoy is a CTLA-4 tumor immunotherapy with an active drug component of ipilimumab, a monoclonal antibody that effectively blocks CTLA-4. CTLA-4 is a negative regulator of T cell activation. When Yervoy binds to CTLA-4, it blocks the interaction of CTLA-4 with its ligand CD80/CD86 and enhances T cell activation and proliferation. The therapeutic mechanism of Yervoy’s efficacy in melanoma patients is indirectly through T cell-mediated anti-tumor immune responses. The approved indication for this drug is melanoma. In addition, the Yervoy+Opdivo immune combination has been approved for the treatment of melanoma and renal cell carcinoma.
Development company: Vertex
Global sales in 2017: 980 million US Dollar
Orkambi is a CFTR corrective agent, the indication is cystic fibrosis carrying F508del homozygous mutation, the active pharmaceutical ingredients are ivacaftor and lumacaftor, the former is a CFTR enhancer, by enhancing the cell membrane The CFTR protein channel opening probability promotes chloride transport; the latter is a CFTR corrector that improves the conformational stability of the F508del-CFTR protein and increases the amount of mature protein processed and transported to the cell surface.