Zydus Life Sciences, formerly known as Cadila Healthcare, an Indian multinational pharmaceutical company headquartered in Ahmedabad, and Swiss-based Roche are engaged in a legal battle over Zydus’ pertuzumab biosimilar (Sigrima®), which is based on Roche’s reference drug pertuzumab (Perjeta®). At the same time, Zydus has entered into a licensing agreement with Dr Reddy’s Laboratories to co-market the biosimilar in India.
The biosimilar, developed in-house by Zydus’ research team at the Zydus Research, represents a significant advancement in breast cancer therapy.
Pertuzumab and trastuzumab
Pertuzumab is a human epidermal growth factor receptor type 2 (HER2-) targeted monoclonal antibody that belongs to the class of HER dimerization inhibitors. However, it is designed to bind to a different domain of HER2 receptor than trastuzumab (Herceptin®; Roche). Studies have shown that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. Additional investigations have demonstrated that pertuzumab preferentially binds to two HER2 proteins, one per Fab fragment, while trastuzumab generally forms a monovalent complex.[1] However, both agents have complementary antitimopr activity and act synergistically in inhibiting the growth of HER2-overexpressing breast cancer cells.[2]
Creating a biosimilar
Zydus and Roche have been at odds since the former tried to create a biosimilar to pertuzumab. Earlier, Roche filed a complaint to the Drugs Controller General of India (DGCI), alleging that Zydus procured the reference drug from an unauthorized supply chain to conduct the clinical trials. Roche also files a complaint for a formulation patent infringement. However, Roche does not currently hold a product patent for pertuzumab in India and It Zydus’ Pertuzumab biosimilar was approved by the Central Drugs Standard Control Organization (CDSCO) in April 2024 and permitted for sale in June 2024.
Breast cancer in India
“As cases of human epidermal growth factor receptor 2-positive (HER2+) breast cancer. rise in India, the conflict between Zydus and Roche underscores the critical need for cost-effective biosimilars to provide broader access to life-saving treatments,” noted Jithendra Kancharla, Pharma Analyst at data and analytics company GlobalData’s Pharmaceutical Intelligence Center.
According to GlobalData, the number of five-year diagnosed prevalent cases of HER2+ breast cancer in India is expected to increase at an annual growth rate (AGR) of 2.43% from 114,393 in 2024 to 139,486 in 2033. India has the second-highest AGR among the major markets*, next only to China.
“Breast cancer is the most prevalent cancer among women in India. HER2+ cases account for nearly 15-20% of breast cancer cases,” Kancharla explained..
“The available treatments are antibodies targeting HER2, like trastuzumab and pertuzumab, and combinations of these with different chemotherapeutic agents. Pertuzumab, when used in combination with trastuzumab and a chemotherapeutic agent, provides a synergistic effect and clinical results show better progression-free survival and overall survival rates compared to these therapies used alone,” he added.
Licensing agreement
In July 2024, Zydus Lifesciences entered into a licensing agreement with Dr Reddy’s Laboratories to co-market in India the pertuzumab biosimilar. Under the terms of the agreement, Zydus will market the product under the brand name Sigrima®, while Dr Reddy will market it as Womab®.
As part of the agreement, Dr Reddy’s will receive semi-exclusive rights from Zydus to co-market the product in India. Zydus will receive upfront licensing income and is eligible to receive milestone income based on the achievement of pre-defined milestones. The collaboration between Dr Reddy’s and Zydus aims to broaden access to this essential medication for patients across India, leveraging the strengths of both companies in distribution and market reach.
Exclusive therapies are costly
Globally, most biologics, including pertuzumab and trastuzumab have a relatively high price tag compared with traditional cytotoxic chemotherapy. In India, for example, Roche’s Herclon® (Trastuzumab); Kadcyla® (trastuzumab emtansine); Perjeta® (pertuzumab) and Phesgo® (pertuzumab + trastuzumab + hyaluronidase) are available at a price range of US $ 730.00 to US $6,396.00
The promise of biosimilars is a significant price reduction compared to the original reference drugs. With the approval of five (5) novel trastuzumab biosimilars at the end of 2019 the general expectation was that this would result in a significant reduction in the overall treatment costs. However, in the United States, the lack of patient’s understanding of therapeutic biosimilars and challenges related to the integration of these biosimilars into regular patient care as well as uncertainty of outcomes from switching patients from the reference drug to the biosimilar have created obstacles for the use of these biosimilars. Hence, while healthcare systems greatly vary, it is important that all stakeholders involved in making treatment decisions, understand how to incorporate biosimilars the care of patients, while, at the same time, healthcare providers are educating the patients about biosimilars. [3]
However, the expectation remains that with an increasing number of approved biosimilars the relative treatment costs will, over the next decade, continue to go down.
Today, some biosimilars marketed by a handful of regional pharmaceutical companies, are available at prices between 30-70% below the costs of the reference drug. For example, the list costs for Zydus’ Vivitra®, a biosimilars of Roche’s Herclon® (trastuzumab), is 41% lower than the reference drug, and the costs of the company’s Ujvira®, a biosimilar for Roche’s Kadcyla® (ado-trastuzumab emtansine), is 70% cheaper than the the reference drug.
“The battle against breast cancer in India is a multifaceted challenge that requires the collective efforts of multinational and local pharmaceutical companies. Both have pivotal roles in driving innovation, improving accessibility, and raising awareness, improving the quality of care for patients across the country, and ultimately saving lives,” said Kancharla,
“The necessity for inexpensive substitutes, such as biosimilars, is urgent given the high price of exclusive targeted therapies. India can address the demands of a greater number of breast cancer patients who require therapy by adopting biosimilars,” he concluded.
Reference
[1] Cruz VL, Souza-Egipsy V, Gion M, Pérez-García J, Cortes J, Ramos J, Vega JF. Binding Affinity of Trastuzumab and Pertuzumab Monoclonal Antibodies to Extracellular HER2 Domain. Int J Mol Sci. 2023 Jul 27;24(15):12031. doi: 10.3390/ijms241512031. PMID: 37569408; PMCID: PMC10418494.
[2] McCormack PL. Pertuzumab: a review of its use for first-line combination treatment of HER2-positive metastatic breast cancer. Drugs. 2013 Sep;73(13):1491-502. doi: 10.1007/s40265-013-0109-0. PMID: 23982598.
[3] Cuellar S. Integrating trastuzumab biosimilars and HER2-directed therapies into HER2-positive breast cancer management. Am J Manag Care. 2020 Mar;26(2 Suppl):S32-S40. doi: 10.37765/ajmc.2020.42900. PMID: 32282173.
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