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Hetero launches darbepoetin alfa biosimilar in India
The Hetero Group, one of the largest manufacturers and suppliers of activepharmaceutical ingredients to the Indian pharmaceutical industry, yesterdayannounced the launch of its first biosimilar product in India, darbepoetin alfa.
This launch marks a significant advancement for Hetero in a biosimilars market expected to grow to US$ 24B in the next five years. In partnership with several prominent pharmaceutical companies, Hetero is launching the drug across India.
http://www.biosimilarnews.com/hetero-launches-darbepoetin-alfa-biosimilar-in-india june 19 2014
Darbepoetin alfa (rINN) /dɑrbəˈpɔɪtɨn/ is a synthetic form of erythropoietin. It stimulates erythropoiesis (increases red blood celllevels) and is used to treat anemia, commonly associated with chronic renal failure and cancer chemotherapy. Darbepoetin is marketed by Amgen under the trade name Aranesp.
The drug was approved in September 2001 by the Food and Drug Administration for treatment of anemia in patients with chronic renal failure by intravenous or subcutaneous injection.[1] In June 2001, it had been approved by the European Medicines Agency for this indication as well as the treatment of anemia in cancer patients undergoing chemotherapy.[2]
Dr. Reddy’s Laboratories launched darbepoetin alfa in India under the brand name ‘Cresp’ in August 2010. This is the world’s first generic darbepoetin alfa. Cresp has been approved in India.
Human erythropoietin with 2 aa substitutions to enhance glycosylation (5 N-linked chains), 165 residues (MW=37 kD). Produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology.
APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQA VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAIS PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR
Darbepoetin is produced by recombinant DNA technology in modified Chinese hamster ovary cells.[citation needed] It differs from endogenous erythropoietin (EPO) by containing two more N-linked oligosaccharide chains. It is an erythropoiesis-stimulating 165-amino acid protein.
Like EPO, its use increases the risk of cardiovascular problems, including cardiac arrest, arrhythmia, hypertension and hypertensive encephalopathy, congestive heart failure, vascular thrombosis or ischemia, myocardial infarction, edema, and stroke. It can also increase risk of seizures. A recent study has extended these findings to treatment of patients exhibiting cancer-related anemia (distinct from anemia resulting from chemotherapy).[3] Pre-existing untreated hypertension is a contra-indication for darbepoetin, as well as some hematologic diseases. Other reported adverse reactions include hypotension, fever, chest pains, nausea and myalgia.
Like EPO, it has the potential to be abused by athletes seeking a competitive advantage. Its use during the 2002 Winter Olympic Games to improve performance led to the disqualification of cross-country skiers Larisa Lazutina and Olga Danilova of Russia and Johann Mühlegg of Spain from their final races.
Safety advisories in anemic cancer patients
Amgen sent a “dear doctor” letter in January, 2007, that highlighted results from a recent anemia of cancer trial, and warned doctors to consider use in that off-label indication with caution.
Amgen advised the U.S. Food and Drug Administration (FDA) as to the results of the DAHANCA 10 clinical trial. The DAHANCA 10 data monitoring committee found that 3-year loco-regional control in subjects treated with Aranesp was significantly worse than for those not receiving Aranesp (p=0.01).
In response to these advisories, the FDA released a Public Health Advisory[4] on March 9, 2007, and a clinical alert[5] for doctors on February 16, 2007, about the use of erythropoeisis-stimulating agents such as epogen and darbepoetin. The advisory recommended caution in using these agents in cancer patients receiving chemotherapy or off chemotherapy, and indicated a lack of clinical evidence to support improvements in quality of life or transfusion requirements in these settings.
In addition, on March 9, 2007, drug manufacturers agreed to new “black box” warnings about the safety of these drugs. On November 8, 2007, additional “black box” warnings were included on the aranesp label, at the request of the FDA.
On March 22, 2007, a congressional inquiry into the safety of erythropoeitic growth factors was reported in the news media. Manufacturers were asked to suspend drug rebate programs for physicians and to also suspend marketing the drugs to patients.
Business considerations for drug manufacturers
| Property | Value | Source |
|---|---|---|
| melting point | 53 °C | Arakawa, T. et al., Biosci. Biotechnol. Biochem. 65:1321-1327 (2001) |
| Country | Patent Number | Approved | Expires (estimated) |
|---|---|---|---|
| Canada | 2165694 | 2003-03-18 | 2010-10-15 |
| Canada | 2147124 | 2002-11-05 | 2014-08-16 |
Epogen and Darbepoetin alfa had more than $6 billion in combined sales in 2006. Procrit sales were about $3.2 billion in 2006.
| Clinical data | |
|---|---|
| AHFS/Drugs.com | monograph |
| MedlinePlus | a604022 |
| Licence data | EMA:Link, US FDA:link |
| Pregnancy cat. | B3 (AU) |
| Legal status | Prescription Only (S4) (AU) |
| Identifiers | |
| CAS number | 11096-26-7  |
| ATC code | B03XA02 |
| DrugBank | DB00012 |
| Chemical data | |
| Formula | C815H1317N233O241S5 |
| Mol. mass | 18396.1 g/mol |
Aranesp (darbepoetin alfa) is an erythropoiesis-stimulating protein that is produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Aranesp is a 165-amino acid protein that differs fromrecombinant human erythropoietin in containing 5 N-linked oligosaccharide chains, whereas recombinant human erythropoietin contains 3 chains. The 2 additional N-glycosylation sites result from amino acid substitutions in the erythropoietin peptide backbone. The approximate molecular weight of darbepoetin alfa is 37,000 daltons.
Aranesp is formulated as a sterile, colorless, preservative-free solution containing polysorbate for intravenous or subcutaneous administration. Each 1 mL contains polysorbate 80 (0.05 mg), sodium chloride (8.18 mg), sodium phosphate dibasic anhydrous (0.66 mg), and sodium phosphate monobasic monohydrate (2.12 mg) in Water for Injection, USP (pH 6.2 ± 0.2).
What are the possible side effects of darbepoetin alfa (Aranesp, Aranesp Albumin Free, Aranesp SureClick)?
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Contact your doctor if you feel light-headed or unusually weak or tired. These may be signs that your body has stopped responding to darbepoetin alfa.
Darbepoetin alfa can increase your risk of life-threatening heart or circulation problems, including heart attack or stroke. This risk will increase the longer you use darbepoetin alfa. Seek emergency medical help if you…
Read All Potential Side Effects and See Pictures of Aranesp »
What are the precautions when taking darbepoetin alfa (Aranesp)?
Before using darbepoetin alfa, tell your doctor or pharmacist if you are allergic to it; or to other drugs that cause more red blood cells to be made (e.g., epoetin alfa); or to products containing human albumin; or if you have any other allergies. This product may contain inactive ingredients (such as polysorbate, latex), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood pressure, blood disorders (e.g., sickle cell anemia, white blood cell or platelet problems, bone marrow problems), bleeding/clotting problems, blood vessel problems (e.g., stroke), heart problems (e.g., angina, heart failure), seizure disorder, a certain…
References
- Jay P. Siegel (2001-09-17). “Product Approval Information – Licensing Action”. United States Food and Drug Administration. Archived from the original on 2006-10-22. Retrieved 2007-01-27.
- “European Public Assessment Report (Abstract)” (PDF). European Medicines Agency. 2001-06-08. Retrieved 2007-01-27.
- Pollack, Andrew (2007-01-26). “Amgen Finds Anemia Drug Holds Risks in Cancer Use”. The New York Times. Retrieved 2007-01-27.
- “FDA Public Health Advisory: Erythropoiesis-Stimulating Agents (ESAs): Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp)”. Archived from the original on 2007-05-28. Retrieved 2007-06-05.
- “Information for Healthcare Professionals: Erythropoiesis Stimulating Agents (ESA)”. Archived from the original on 2007-05-15. Retrieved 2007-06-05.
Molecular biology mystery unravelled
The nature of the machinery responsible for the entry of proteins into cell membranes has been unravelled by scientists, who hope the breakthrough could ultimately be exploited for the design of new anti-bacterial drugs. Groups of researchers from the University of Bristol and the European Molecular Biology Laboratory (EMBL) used new genetic engineering technologies to reconstruct and isolate the cell’s protein trafficking machinery.
Its analysis has shed new light on a process which had previously been a mystery for molecular biologists.
The findings, published today in the Proceedings of the National Academy of Sciences(PNAS), could also have applications for synthetic biology – an emerging field of science and technology, for the development of novel membrane proteins with useful activities.
Proteins are the building blocks of all life and are essential for the growth of cells and tissue repair. The proteins in the membrane typically help the cell…
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An off-switch for drugs’ toxic side effects
When medications linger in the human body, they sometimes produce toxic side effects. Professor Alexandros Makriyannis, the George D. Behrakis Trustee Chair in Pharmaceutical Biotechnology and Director of the Center for Drug Discovery at Northeastern, explained that many things can happen to a drug inside our bodies once it is ingested. For instance, the drug can be modified into other byproducts with their own undesirable and unpredictable effects. Or it can remain embedded in the body’s fatty tissues and then be slowly released into the circulatory system.
“If you had a way of controlling how long this drug sits in the body,” Makriyannis said, “that would be a beneficial effect. It would be a safer drug.”
In research recently published in the Journal of Medicinal Chemistry and Medicinal Chemistry Letters, Makriyannis and his team present not just one such drug but a whole series of them. “We call…
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Quantum biology: Algae evolved to switch quantum coherence on and off
A scanning electron microscope image of cryptophytes. A UNSW Australia-led team has discovered how cryptophytes that survive in very low levels of light are able to switch on and off a weird quantum phenomenon that occurs during photosynthesis. Credit: CSIRO
A UNSW Australia-led team of researchers has discovered how algae that survive in very low levels of light are able to switch on and off a weird quantum phenomenon that occurs during photosynthesis.
The function in the algae of this quantum effect, known as coherence, remains a mystery, but it is thought it could help them harvest energy from the sun much more efficiently. Working out its role in a living organism could lead to technological advances, such as better organic solar cells and quantum-based electronic devices.
The research is published in the journal Proceedings of the National Academy of Sciences.
It is part of an emerging field called…
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Ebola outbreak in West Africa ‘out of control’
A senior official for Doctors Without Borders says the Ebola outbreak ravaging West Africa is “totally out of control” and that the medical group is stretched to the limit in its capacity to respond.
Bart Janssens, the director of operations for the group in Brussels, said Friday that international organizations and the governments involved need to send in more health experts and increase public education messages about how to stop the spread of the disease.
Janssens said the outbreak is far from over and will probably end up as the most deadly on record.
According to the latest figures from the World Health Organization, Ebola has already been linked to more than 330 deaths in Guinea, Sierra Leone and Liberia.
Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?
Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?
Author: Larry H. Bernstein, MD, FCAP
A Critical Review
What is the Warburg effect?
“Warburg Effect” describes the preference of glycolysis and lactate fermentation rather than oxidative phosphorylation for energy production in cancer cells. Mitochondrial metabolism is an important and necessary component in the functioning and maintenance of the organelle, and accumulating evidence suggests that dysfunction of mitochondrial metabolism plays a role in cancer. Progress has demonstrated the mechanisms of the mitochondrial metabolism-to-glycolysis switch in cancer development and how to target this metabolic switch.
In vertebrates, food is digested and supplied to cells mainly in the form of glucose. Glucose is broken down further to make Adenosine Triphosphate (ATP) by two pathways. One is via anaerobic metabolism occurring in the cytoplasm, also known as glycolysis. The major physiological significance of glycolysis lies in making ATP…
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A better imager for identifying tumors
This is (a) Optical and mechanical structure of the customized lens with aperture filter and (b) the photograph of the assembled lens, with a quarter for comparison. Credit: Optics Letters
Before they excise a tumor, surgeons need to determine exactly where the cancerous cells lie. Now, research published today in The Optical Society’s (OSA) journal Optics Letters details a new technique that could give surgeons cheaper and more lightweight tools, such as goggles or hand-held devices, to identify tumors in real time in the operating room.
The new technology, developed by a team at the University of Arizona and Washington University in St. Louis, is a dual-mode imager that combines two systems—near-infrared fluorescent imaging to detect marked cancer cells and visible light reflectance imaging to see the contours of the tissue itself—into one small, lightweight package approximately the size of a quarter in diameter, just 25 millimeters across.
“Dual modality is…
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Developing an improved liposuction technique that melts fat
Although liposuction is one of the most common and well-established cosmetic surgery procedures in the U.S., it still has its drawbacks. But a new biomedical start-up says it may have found a novel way to improve the procedure using gold nanoparticles to literally melt fat, reports Chemical & Engineering News (C&EN), the weekly news magazine of the American Chemical Society.
Lauren K. Wolf, an associate editor at C&EN, explains that during the most common type of liposuction procedure, a surgeon inserts a sharp-edged needle through an incision, moves it back and forth to break up fat cells and then vacuums them out. The problem is the procedure isn’t selective, and sometimes connective tissue and nerves get removed along with the fat cells. Liposuction patients often suffer from bruising, long recovery times and lumpiness that has to be corrected with a second procedure. To address the surgery’s problems, a…
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Do salamanders hold the key to limb regeneration?
This is an image of a salamander (the newt Notophthalmus viridescens). Credit: University College London
The secret of how salamanders successfully regrow body parts is being unravelled by University College London researchers in a bid to apply it to humans.
For the first time, researchers have found that the ‘ERK pathway’ must be constantly active for salamander cells to be reprogrammed, and hence able to contribute to the regeneration of different body parts.
The team identified a key difference between the activity of this pathway in salamanders and mammals, which helps us to understand why humans can’t regrow limbs and sheds light on how regeneration of human cells can be improved.
The study published in Stem Cell Reports today, demonstrates that the ERK pathway is not fully active in mammalian cells, but when forced to be constantly active, gives the cells more potential for reprogramming and regeneration. This could…
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Computer-designed protein triggers self-destruction of Epstein-Barr-infected cancer cells
A small chunk of protein (red) bound to the Epstein-Barr virus target protein (gray) was extended to make a much longer protein, left, and then designed to have a rigid folded structure, right, for tight and specific interactions with the target. Credit: University of Washington
A protein molecule, “BINDI,” has been built to trigger self-destruction of cancer cells infected with the Epstein-Barr virus. Numerous cancers are linked to the Epstein-Barr virus, which can disrupt the body’s weeding of old, abnormal, infected and damaged cells.
The Epstein-Barr virus persists for a long time after a bout with mononucleosis or other diseases for which it is responsible. It survives by preventing cells from disintegrating to kill themselves and their invaders. The virus’ interference with cell population control may contribute to cancerous overgrowth.
In a June 19 report in the scientific journal Cell, researchers describe how they computer-designed, engineered and tested a…
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DR ANTHONY MELVIN CRASTO
ORGANIC SPECTROSCOPY
New Drug Approvals 