Nimotuzumab
Encyclopedia
Nimotuzumab is a humanized monoclonal antibody used to treat squamous cell carcinomas of the head and neck, recurrent or refractory high grade malignant glioma
, anaplastic astrocytomas, glioblastomas and diffuse intrinsic pontine glioma.
Like cetuximab
, nimotuzumab binds to the epidermal growth factor receptor
(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.
Most monoclonal antibodies are originally created by mouse cells, but this can cause an immune reaction to mouse proteins. Humanised antibodies are made using parts of mouse proteins and parts of human proteins, which causes less of an immune reaction. Nimotuzumab contains 95% human antibody sequences. This reduces adverse effects such as rash, diarrhea
and conjunctivitis
.
and chemotherapy
.
(CIM) in Havana
, Cuba
.
The Center of molecular immunology
with YM Biosciences and its licensees are committed to the clinical development and subsequent marketing of nimotuzumab. These include Daiichi-Sankyo Co. Ltd. in Japan
, Oncoscience AG in Europe, Kuhnil Pharmaceutical Co., Ltd. in South Korea
and Innogene Kalbiotech Pte Ltd. in South East Asia. In addition, as of November 30, 2007 eight other companies around the globe were involved in a consortium with CIM and YM or with their licensees, or unilaterally in a number of trials in multiple indications. Other licensees for nimotuzumab include Biocon BioPharmaceuticals Ltd. (BBPL) in India
, Biotech Pharmceutical Co. Ltd. in China
, Delta Laboratories in Colombia
, European Chemicals SAC – Corporación Infarmasa SA in Peru
, Eurofarma Laboratorios Ltda. in Brazil
, Ferozsons Labs in Pakistan
, Laboratorio Elea S.A.C.I.F.yA. in Argentina
, EL KENDI Pharmaceutical in Algeria and Laboratorios PiSA in Mexico
.
Nimotuzumab has been administered to more than 4,400 patients worldwide through commercial sales and is currently in a phase II clinical trial in United States and Canada.
and debilitating skin rashes were absent in patients treated with Nimotuzumab . Classical EGFR inhibition related side effects were also negligible. The improved safety results without compromising on efficacy can be attributed to its unique molecular profile.
All adverse events were mild to moderate and were considered infusion reactions. No patient developed acneiform rash or other dermatological toxicity. Grade 3 somnolence was reported in one patient following a 400 mg dose of nimotuzumab.
In a phase II trial, the most common adverse reactions were fever (4.28%), dizziness and hypotension (2.86%) and mild skin rash (1.43%).
These adverse reactions respond to treatment with conventional doses of analgesic
and antihistaminics.
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
, anaplastic astrocytomas, glioblastomas and diffuse intrinsic pontine glioma.
Like cetuximab
Cetuximab
Cetuximab is a chimeric monoclonal antibody, an epidermal growth factor receptor inhibitor, given by intravenous infusion for treatment of metastatic colorectal cancer and head and neck cancer.- Distribution :Cetuximab is manufactured and distributed in North America by ImClone and Bristol-Myers...
, nimotuzumab binds to the epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
(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.
Most monoclonal antibodies are originally created by mouse cells, but this can cause an immune reaction to mouse proteins. Humanised antibodies are made using parts of mouse proteins and parts of human proteins, which causes less of an immune reaction. Nimotuzumab contains 95% human antibody sequences. This reduces adverse effects such as rash, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
and conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
.
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 therapyRadiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
and chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
.
Development status
It was developed at the Center of molecular immunologyCenter of molecular immunology
The Center of Molecular Immunology or CIM, is a cancer research institution located on the west side of Havana, Cuba...
(CIM) in Havana
Havana
Havana is the capital city, province, major port, and leading commercial centre of Cuba. The city proper has a population of 2.1 million inhabitants, and it spans a total of — making it the largest city in the Caribbean region, and the most populous...
, Cuba
Cuba
The Republic of Cuba is an island nation in the Caribbean. The nation of Cuba consists of the main island of Cuba, the Isla de la Juventud, and several archipelagos. Havana is the largest city in Cuba and the country's capital. Santiago de Cuba is the second largest city...
.
The Center of molecular immunology
Center of molecular immunology
The Center of Molecular Immunology or CIM, is a cancer research institution located on the west side of Havana, Cuba...
with YM Biosciences and its licensees are committed to the clinical development and subsequent marketing of nimotuzumab. These include Daiichi-Sankyo Co. Ltd. in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, Oncoscience AG in Europe, Kuhnil Pharmaceutical Co., Ltd. in South Korea
South Korea
The Republic of Korea , , is a sovereign state in East Asia, located on the southern portion of the Korean Peninsula. It is neighbored by the People's Republic of China to the west, Japan to the east, North Korea to the north, and the East China Sea and Republic of China to the south...
and Innogene Kalbiotech Pte Ltd. in South East Asia. In addition, as of November 30, 2007 eight other companies around the globe were involved in a consortium with CIM and YM or with their licensees, or unilaterally in a number of trials in multiple indications. Other licensees for nimotuzumab include Biocon BioPharmaceuticals Ltd. (BBPL) in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
, Biotech Pharmceutical Co. Ltd. in China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
, Delta Laboratories in Colombia
Colombia
Colombia, officially the Republic of Colombia , is a unitary constitutional republic comprising thirty-two departments. The country is located in northwestern South America, bordered to the east by Venezuela and Brazil; to the south by Ecuador and Peru; to the north by the Caribbean Sea; to the...
, European Chemicals SAC – Corporación Infarmasa SA in Peru
Peru
Peru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean....
, Eurofarma Laboratorios Ltda. in Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
, Ferozsons Labs in Pakistan
Pakistan
Pakistan , officially the Islamic Republic of Pakistan is a sovereign state in South Asia. It has a coastline along the Arabian Sea and the Gulf of Oman in the south and is bordered by Afghanistan and Iran in the west, India in the east and China in the far northeast. In the north, Tajikistan...
, Laboratorio Elea S.A.C.I.F.yA. in Argentina
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...
, EL KENDI Pharmaceutical in Algeria and Laboratorios PiSA in Mexico
Mexico
The United Mexican States , commonly known as Mexico , is a federal constitutional republic in North America. It is bordered on the north by the United States; on the south and west by the Pacific Ocean; on the southeast by Guatemala, Belize, and the Caribbean Sea; and on the east by the Gulf of...
.
Nimotuzumab has been administered to more than 4,400 patients worldwide through commercial sales and is currently in a phase II clinical trial in United States and Canada.
Safety
The toxicity and safety of nimotuzumab have been assessed in several pre-clinical and clinical studies wherein it was noticed that side effects such as hypomagnesemiaHypomagnesemia
Hypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood. Usually a serum level less than 0.7 mmol/L is used as reference. The prefix hypo- means low . The middle 'magnes' refers to magnesium...
and debilitating skin rashes were absent in patients treated with Nimotuzumab . Classical EGFR inhibition related side effects were also negligible. The improved safety results without compromising on efficacy can be attributed to its unique molecular profile.
Safety in pre-clinical experiments
- Nimotuzumab did not produce any significant acute toxicity following single administration of up to 10 times the dose proposed for clinical trialClinical trialClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s. - No treatment-related systemic toxicity was observed in animals after administering nimotuzumab once daily for 14 days.
Safety profile in clinical trials
Nimotuzumab has been found to be very well tolerated in clinical trials. Common adverse reactions seen in patients treated with nimotuzumab include:- Chills
- FeverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
- NauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomitingVomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose... - Dryness of mouth
- Asthenia
- HypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
/hypotensionHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the... - Flushing
All adverse events were mild to moderate and were considered infusion reactions. No patient developed acneiform rash or other dermatological toxicity. Grade 3 somnolence was reported in one patient following a 400 mg dose of nimotuzumab.
In a phase II trial, the most common adverse reactions were fever (4.28%), dizziness and hypotension (2.86%) and mild skin rash (1.43%).
These adverse reactions respond to treatment with conventional doses of analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
and antihistaminics.