NIMOTUZUMAB
Nimotuzumab is a recombinant monoclonal antibody that selectively targets and is active against cells that over-express EGFR, such as tumour cells, whereas activity against normal healthy cells (e.g.: skin) with low EGFR expression is limited, thereby avoiding unwanted toxicities. Nimotuzumab can be used as a monotherapy and in combination with radiation therapy and/or chemotherapy for the treatment of malignant diseases and is the only-affinity optimized™ anti-EGFR monoclonal antibody exhibits superior safety profile among the class of anti-EGFR agents [1].
Nimotuzumab was invented at the Center of Molecular Immunology (CIM) in Havana, Cuba and co-developed by YM Biosciences (currently a subsidiary of Gilead) in Canada. Today Nimotuzumab is approved in 30 non-ICH in Asia, South America and Africa for the treatment of squamous cell carcinomas of the head and neck, oesophageal cancer, refractory paediatric and adult glioma, nasopharyngeal carcinoma and pancreatic cancer. Nimotuzumab has orphan drug status in the US and EU for paediatric glioma (Diffuse Intrinsic Pontine Glioma) and pancreatic cancer.
Nimotuzumab is a humanized monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR). EGFR targeting drugs have been shown to improve response when used with conventional treatments such as radiation therapy and chemotherapy.
Knowledge of the epidermal growth factor receptor’s (EGFR) function in the malignant process has advanced enormously during the past decade. Its overexpression has been better characterized in different tumour types, but also linked to a worse patient prognosis as well as radiotherapy and chemotherapy resistance. Additionally, the EGFR signalling pathway is known to contribute to tumour proliferation, apoptosis resistance, angiogenesis, invasion and metastasis.
Experiments have shown that nimotuzumab requires bivalent binding (attachment with both antibody arms to two EGF receptors) for efficient accumulation on cellular surface. The ability to form bivalent bonds is a function of EGFR density on the cellular surface. The selective accumulation of nimotuzumab on cancer cells over-expressing the EGFR is a mechanistic explanation for the very low incidence of side-effects with this antibody.
A total of 35 clinical trials have been completed with nimotuzumab on several cancer indications:
- Eight (8) trials in squamous cell carcinoma of the head and neck
- Canada, Cuba, and India.
- Eight (8) trials in Glioma
- Cuba, Germany, Canada and India.
- Five (5) trials in non-small cell lung cancer
- Canada, Cuba, India and Japan.
- Three (3) in esophageal cancer
- Cuba, Brazil and China.
- Two (2) in solid tumours
- Canada and Japan.
- Two (2) in pancreatic cancer
- Germany.
- One (1) in colorectal cancer
- Canada.
- One (1) in breast cancer
- Cuba.
- One (1) in tumours of epithelial origin
- Cuba.
- One (1) in prostate cancer
- Cuba.
- One (1) in hepatic cancer
- Cuba.
- One (1) in gastric cancer
- Japan and South Korea.
- One (1) in nasopharyngeal cancer
- China.
The clinical development program includes an additional 27 clinical trials currently ongoing to investigate the safety and efficacy of nimotuzumab in 11 different localizations, breast, cervical, colorectal, esophageal, gastric, adult and pediatric glioma, head and neck, nasopharyngeal, non-small cell lung, prostate cancers and solid tumors.
To date (2015) over 2705 patients have been enrolled in the completed clinical trials, 1939 of them were treated with nimotuzumab and 766 were included on the control group and nearly 4580 more are planned for inclusion in the ongoing studies from them 2601 have been already included.