Nimotuzumab (h-R3, BIOMAb EGFR, Biocon, India; TheraCIM, CIMYM Biosciences, Canada; Theraloc, Oncoscience, Europe, CIMAher, Center of Molecular Immunology, Havana, Cuba) is a humanized

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

that as of 2014 had orphan status in the US and EU for

glioma A glioma is a type of primary tumor that starts in the glial cells of the brain or spinal cord. They are malignant but some are extremely slow to develop. Gliomas comprise about 30% of all brain and central nervous system tumors and 80% of ...

, and marketing approval in India, China, and other countries for squamous cell carcinomas of the head and neck, and was undergoing several clinical trials. Like

cetuximab Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer. Cetuximab is a chimeric (mouse/human) monoclonal a ...

, nimotuzumab binds to the

epidermal growth factor receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor (biochemistry), receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligand (biochemistry ...

(EGFR), a signalling protein that normally controls cell division. In some cancers, this receptor is altered to cause uncontrolled cell division, a hallmark of cancer. These monoclonal antibodies block EGFR and stop the uncontrolled cell division. It has a

humanized Humanized antibodies are antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans. The process of "humanization" is usually applied to monoclonal ant ...

human-mouse h-R3 heavy chain and a humanized human-mouse h-R3 κ-chain.Merck Index 14th Edition Monograph number 10585.

Mechanism

Nimotuzumab binds with optimal affinity and high specificity to the extracellular region of EGFR (epidermal growth factor receptor). This results in a blockade of ligand binding and receptor activation. Epidermal growth factor receptor (EGFR) is a key target in the development of cancer therapeutics. EGFR-targeting drugs have been shown to improve response when used with conventional treatments such as

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

and

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

Development status

It was developed at the Center of molecular immunology (CIM) in

Havana Havana (; ) is the capital and largest city of Cuba. The heart of La Habana Province, Havana is the country's main port and commercial center.Cuba Cuba, officially the Republic of Cuba, is an island country, comprising the island of Cuba (largest island), Isla de la Juventud, and List of islands of Cuba, 4,195 islands, islets and cays surrounding the main island. It is located where the ...

. CIM's commercialization arm, CIMAB S.A. formed a joint venture with YM Biosciences called CIMYM BioSciences in 1995 that was 80% owned by YM and 20% owned by CIMAB.YM Bioscience
YM Biosciences Annual Report for year ended June 30, 2007
CIMYM BioSciences licensed European rights to nimotuzumab to

Oncoscience AG Oncology is a branch of medicine that deals with the study, treatment, diagnosis, and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''� ...

in 2003, the South Korean rights to Kuhnil Pharmaceutical Co., Ltd. in 2005, and in 2006, licensed the Japanese rights to

Daiichi Sankyo is a global pharmaceutical company and the second-largest pharmaceutical company in Japan. It achieved JPY 1,278 billion in revenue in 2022. The company owns the American pharmaceutical company American Regent. Daiichi Sankyo, Inc. (DSI) began ...

and rights to certain countries in Asia and Africa to Innogene Kalbiotech Pte Ltd. Other licensees for nimotuzumab include Biocon BioPharmaceuticals Ltd. (BBPL) in

India India, officially the Republic of India, is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area; the List of countries by population (United Nations), most populous country since ...

, Biotech Pharmaceutical Co. Ltd. in

China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...

, Delta Laboratories in

Colombia Colombia, officially the Republic of Colombia, is a country primarily located in South America with Insular region of Colombia, insular regions in North America. The Colombian mainland is bordered by the Caribbean Sea to the north, Venezuel ...

, European Chemicals SAC, Quality Pharma in

Peru Peru, officially the Republic of Peru, is a country in western South America. It is bordered in the north by Ecuador and Colombia, in the east by Brazil, in the southeast by Bolivia, in the south by Chile, and in the south and west by the Pac ...

Eurofarma Laboratorios Ltda
in

Brazil Brazil, officially the Federative Republic of Brazil, is the largest country in South America. It is the world's List of countries and dependencies by area, fifth-largest country by area and the List of countries and dependencies by population ...

, Ferozsons Labs in

Pakistan Pakistan, officially the Islamic Republic of Pakistan, is a country in South Asia. It is the List of countries and dependencies by population, fifth-most populous country, with a population of over 241.5 million, having the Islam by country# ...

, Laboratorio Elea S.A.C.I.F.yA. in

Argentina Argentina, officially the Argentine Republic, is a country in the southern half of South America. It covers an area of , making it the List of South American countries by area, second-largest country in South America after Brazil, the fourt ...

, EL KENDI Pharmaceutical in Algeria and Laboratorios PiSA in

Mexico Mexico, officially the United Mexican States, is a country in North America. It is the northernmost country in Latin America, and borders the United States to the north, and Guatemala and Belize to the southeast; while having maritime boundar ...

. In December 2012, CIMYM BioSciences dissolved and sold its assets related to nimotuzumab to InnoKeys PTE Ltd. According to a 2009 review: "Nimotuzumab was approved for the following indications—For

squamous cell carcinoma Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...

in head and neck (SCCHN) in India, Cuba, Argentina, Colombia, Ivory Coast, Gabon, Ukraine, Peru and Sri Lanka (expired now); for

(pediatric and adult) in Cuba, Argentina, Philippines and Ukraine; for

nasopharyngeal cancer Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess ( fossa of Rosenmüller), accounting for 50% of cases. NPC occur ...

in China. It has been granted orphan drug status for glioma in USA and for glioma and

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...

in Europe." As of 2014 Nimotuzumab was in additional Phase I and II clinical trials. In April 2014, Daiichi Sankyo announced that it was halting a multicenter, randomized, double-blind, placebo-controlled Phase III study investigating nimotuzumab for first-line therapy in patients with unresectable and locally advanced squamous cell lung cancer, due to safety issues in certain patients who received a combination of cisplatin, vinorelbine, radiotherapy, and nimotuzumab.

Safety

The toxicity and safety of nimotuzumab have been assessed in several pre-clinical and clinical studies wherein it was noticed that side effects usually caused by EGFR inhibitors, especially rashes and other skin toxicities, were negligible. Scientists have hypothesized that this is because nimotuzumab binds only to cells that express moderate to high EGFR levels. Nimotuzumab has been found to be very well tolerated in clinical trials. Common adverse reactions seen in patients treated with nimotuzumab include:BioMab Insert
/ref> *Chills *

Fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

Nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

and

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

*Dryness of mouth *

Asthenia Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, ...

Hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

*Flushing

Notes

{{Growth factor receptor modulators Monoclonal antibodies for tumors Cuban inventions