In last November Biocon announced that it has received the marketing authorization from the DCGI for its novel biosimilar trastuzumab, a monoclonal antibody that interferes with the HER2/neu receptor and used for the treatment of certain breast cancer, viz. HER2+ metastatic breast cancer.
Trastuzumab belongs to a class of drugs called monoclonal antibodies. The company started developing trastuzumab jointly with Mylan Inc. Biocon stated that the regulatory approval for trastuzumab in India is an important milestone for the company as it is the world’s first biosimilar version of Herceptin of Roche to be brought to the market. The trastuzumab will be marketed in India under the brand name of CANMAb and is expected to be available to Indian patients in the fourth quarter of the financial year 2014.
It is reported that trastuzumab improves overall survival in late-stage (metastatic) breast cancer within 20.3 to 25.1 months. In early stage breast cancer, it reduces the risk of cancer returning after surgery by an absolute risk of 9.5%, and the risk of death by an absolute risk of 3% however it may increases serious heart problems by an absolute risk of 2.1% which may resolve if treatment is stopped [Ref. Moja L, Tagliabue L, Balduzzi S, et al. (2012).
"Trastuzumab containing regimens for early breast cancer". Cochrane Database Syst Rev 4: CD006243. doi:10.1002/14651858.CD006243.pub2. PMID 22513938].Trastuzumab is also being studied for the treatment of other cancers (Ref. Vecchione L. Novel investigational drugs for gastric cancer. Expert Opin Investig Drugs. 2009 May 26. [Epub ahead of publication]. Review/article). It has been used with some success in women with uterine papillary serous carcinomas that over express HER2/neu.[Ref. Santin AD, Bellone S, Roman JJ, McKenney JK, Pecorelli S. (2008). "Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma over expressing HER2/neu". Int. J. Gynaecol Obstet. 102 (2): 128–31. doi:10.1016/ j.ijgo. 2008.04.008].
Breast cancer is one of the most common types of cancer in India with over 100,000 new breast cancer patients being diagnosed with this disease every year. The cost of biologics in cancer treatment is extremely high which makes access unaffordable to a large patient pool. Biosimilar trastuzumab will offer an alternative affordable option thereby enhancing access to treatment for cancer patients in India and world over, says Biocon. It may be noted that the global sales for trastuzumab stood at US$ 6.4 billion in 2012, while in India it recorded sales of US$ 21 million.
The meticulous development of this important cancer drug has involved extensive product characterization and clinical trials to demonstrate comparability and similarity in pharmacokinetic, safety, efficacy and immunogenicity against the innovator product. We are committed to affordable cancer care and believe that trastuzumab will expand patient access to this life saving drug. The Indian approval is an encouraging milepost as we plan to leverage this data to support regulatory filings in several countries across the globe'', "We are committed to affordable cancer care and believe that biosimilar trastuzumab will expand patient access to this life saving drug. The Indian approval is an encouraging milepost as we plan to leverage this data to support regulatory filings in several countries across the globe", says Biocon.
Since 2009, Biocon and Mylan Inc. have been co-developing a high value portfolio of biosimilar monoclonal antibodies and complex biologics, comprising Trastuzumab, Pegfilgrastim, Bevacizumab, Adalimumab and Etanercept. The innovator product sales of these products in 2012 were pegged at US$ 34 billion. The patent expiry of these products in regulated markets is expected from 2015 onwards. In 2013, this partnership with Mylan was extended to co-development of biosimilar insulin analogues for the global markets. The overall global opportunity for biosimilars is estimated to be US$ 22 billion by 2020.
Breast cancer is a malignant tumour that starts in the cells of the breast. A malignant tumour is a group of cancer cells that can grow into (invade) surrounding tissues or spread (metastasize) to distant areas of the body. The female breast is made up mainly of lobules (milk-producing glands), ducts (tiny tubes that carry the milk from the lobules to the nipple), and stroma (fatty tissue and connective tissue surrounding the ducts and lobules, blood vessels, and lymphatic vessels). Most breast cancers begin in the cells that line the ducts (ductal cancers). Some begin in the cells that line the lobules (lobular cancers), while a small number start in other tissues.
The lymph system is important to understand because it is one way breast cancers can spread. This system has several parts. Lymph nodes are small, bean-shaped collections of immune system cells (cells that are important in fighting infections) that are connected by lymphatic vessels. Lymphatic vessels are like small veins, except that they carry a clear fluid called lymph (instead of blood) away from the breast. Lymph contains tissue fluid and waste products, as well as immune system cells. Breast cancer cells can enter lymphatic vessels and begin to grow in lymph nodes.
Most lymphatic vessels in the breast connect to lymph nodes under the arm (axillary nodes). Some lymphatic vessels connect to lymph nodes inside the chest (internal mammary nodes) and those either above or below the collarbone (supraclavicular or infraclavicular nodes).
If the cancer cells have spread to lymph nodes, there is a higher chance that the cells could have also gotten into the bloodstream and spread (metastasized) to other sites in the body. The more lymph nodes with breast cancer cells, the more likely it is that the cancer may be found in other organs as well. Because of this, finding cancer in one or more lymph nodes often affects the treatment plan. Still, not all women with cancer cells in their lymph nodes develop metastases, and some women can have no cancer cells in their lymph nodes and later develop metastases.
Doctors choose options to treat breast cancer based on the type of cancer, its stage and grade, sensitivity of the cancer cells to hormones, overall health of the patient and of course on the patient. Women mostly undergo surgery for breast cancer and also receive additional treatment, such as chemotherapy, hormone therapy or radiation. Trastuzumab inhibits the effects of over expression of HER2. Women with HER2-positive early breast cancer favour subcutaneous over intravenous (IV) administration of trastuzumab, according to a report. Trastuzumab, which specifically targets HER2, kills these cancer cells and decreases the risk of recurrence. Trastuzumab is often used with chemotherapy. But it may also be used alone or in combination with hormone-blocking medications, such as an aromatase inhibitor or tamoxifen. Trastuzumab is usually well tolerated, but it does have some potential side-effects, such as congestive heart failure and allergic reaction.
(The author is a practicing chemical engineer based in Mumbai)