The Mayo Clinic reports that one out of every 5 breast cancers are HER2-positive. These cells have a mutation in a gene that codes for the human epidermal growth factor receptor (HER2) causing these cells to produce an abundance of the HER2 protein.

In 1998, Genentech, was the first biotech company to invent and develop a biologic drug, Herceptin (Transtuzumab), to treat metastatic breast cancer and receive FDA approval. A decade or so later, Herceptin was also the first humanized  monoclonal antibody to receive FDA approval for  HER2-positive metastatic cancer of the stomach or gastroesophageal junction, in men and women in combination with chemotherapy (cisplatin plus either capecitabine or 5-fluorouracil). Herceptin works by binding to HER2 receptors on the surface of HER2-positive tumour cells and blocks them from receiving growth signals. The revolutionary discovery of this wonder drug in 1998 made Herceptin the preferred treatment for breast cancer worldwide after Roche received exclusive marketing rights for Herceptin outside the US. Roche acquired Genentech in 2009.

The development of Herceptin and other therapeutic monoclonal antibodies  trace their  history back to the invention of a critical step in the production of monoclonal antibody by scientist Shmuel Cabilly in the early 1980’s when he headed a joint project at the City of Hope and Genentech. Named after him, the ‘Cabilly II’ patents were granted to Roche and the City of Hope as co-assignees. As competitors Eli Lilly, Abbott, Johnson and Johnson, ImClone and MedImmune, AbbVie acquired the license to to make antibody versions of their drug using the process outlined in these patents, it allowed co-owners Roche and the City of Hope to collect royalties from these companies for several years.

Historically, patents on branded drugs have provided several biotech and pharma companies high profits with significantly high margins. In the case of Roche, with EU patents having expired and US patent expiration for Herceptin looming ahead in the summer of 2019, Roche stands to lose significant market share in the coming years. Roche’s Herceptin had sales of 7 Billion Swiss francs in 2017 up 3% from the previous year. To capture a portion of this extremely lucrative pie, several drug development companies globally have entered the fray by developing cheaper versions of branded drugs called biosimilars. Since biotech drugs require massive financial investment and diverse skills along the entire drug development value chain, bringing a generic version to market is no small feat.

The launch of biosimilars will bring a sigh of relief to thousands of breast cancer patients worldwide as these copycat drugs begin to make inroads into different markets. Though Herceptin is still considered the wonder drug, it is extremely expensive and has been highly unaffordable to many, especially in the lower economic strata of emerging markets causing many of them to abandon treatment. While the pricing of biosimilars cannot be compared to small molecule generics, the lower costs will provide an avenue for faster adoption in emerging markets.

Some of the key players in the biosimilar space are Samsung; Mylan and Biocon; Celltrion; Amgen and Allergan. South Korea’s Samsung Bioepis, the biotech arm of the Samsung Group, received marketing authorization from the EU earlier this year for Ontruzant, a biosimilar version of Herceptin.  This will be marketed in the UK through Merck Sharpe and Dohme. Towards the end of 2017, Mylan and its Indian partner, Biocon announced approval by ANVISA, the Brazilian regulatory agency, and will be marketed through their partner Libbs Farmaceutica (Libbs), in Brazil.
Mylan and Biocon’s Herceptin biosimilar is also the first biosimilar to be approved by the US FDA last December for the treatment of breast and metastatic breast cancer. The drug will be marketed in the United States as Ogivri.

References:
mAbs 4:2, 274-280; March/April 2012; © 2012 Landes Bioscience
Roche 2006 Finance Report