Bortezomib API Technology Transfer
Basic Information
Name: Bortezomib
Chemical Name: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic acid
Chemical Structure: (Not provided in text)
Molecular Formula: C19H25BN4O4
Molecular Weight: 384.24
CAS Number: 179324-69-7
Indication: Primarily used for the treatment of multiple myeloma (MM).
Pharmacology:
Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The ubiquitin-proteasome pathway plays a critical role in maintaining cellular homeostasis by regulating the intracellular concentration of specific proteins. Proteolysis affects multiple levels of cellular signaling cascades, and disruption of this process can lead to cell death. Inhibition of the 26S proteasome prevents the degradation of specific proteins. In vitro studies demonstrate that bortezomib is cytotoxic to various cancer cell types. In vivo preclinical tumor models show that bortezomib delays tumor growth, including in multiple myeloma.
Global Market Status: Approved by the U.S. FDA in 2003 for marketing in the United States.
China Market Status: In February 2005, Xian-Janssen received approval for import and distribution in China.
Drug NameGeneric NameManufacturerStrengthUnitVelcadeBortezomib for InjectionXian-Janssen Pharmaceutical Co., Ltd.3.5 mgVial
Domestic Registration: Since 2012, 18 companies have applied for API registration, and 18 for formulation registration, all under review.
Intellectual Property: The compound patent in China expired in 2015.
Market Prospects
Multiple myeloma (MM) is a common malignant plasma cell disorder, accounting for approximately 10% of hematologic malignancies. In China, the incidence rate is about 1 per 100,000 people, with most patients diagnosed between 50–60 years of age, though cases in patients under 40 are not uncommon in China. Conventional chemotherapy controls the disease in 40%–70% of patients, stabilizing the condition for months to years, with a median survival of about 3 years. However, only about 25% of patients survive beyond 5 years, and fewer than 5% survive beyond 10 years.
Over the past 20 years, high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation has significantly improved outcomes for MM patients under 65, with early transplantation outperforming late transplantation and sequential double transplantation outperforming single transplantation. Bortezomib, a novel drug, exerts anti-myeloma effects through multiple innovative mechanisms. Clinical studies abroad have shown bortezomib to be effective for both newly diagnosed and relapsed/refractory MM patients. Bortezomib-based combination chemotherapy regimens are recommended by the National Comprehensive Cancer Network (NCCN) as a primary treatment option (with or without transplantation) and for salvage therapy in MM patients.
With China’s aging population, the incidence of MM is rising, and the age of onset in China is 5–6 years earlier than in Western populations, posing a significant health threat. Without treatment, patients with progressive MM have a median survival of only 6 months. Current treatments are limited in efficacy, with conventional combination chemotherapy achieving a complete remission rate of less than 10% and a median survival of 3–4 years. While allogeneic hematopoietic stem cell transplantation is considered the best curative option, its high transplant-related mortality rate makes it unsuitable for most patients, who are often over 60 years old. Thus, there is an urgent need for new treatment approaches.
Targeted therapies have brought new hope for MM patients. Bortezomib, a novel targeted therapy, has demonstrated anti-MM effects in both in vitro and in vivo studies. Given its indications and clinical efficacy, bortezomib holds significant value for development and research. Once launched in China, it is expected to generate substantial social and economic benefits.
