Monoclonal antibodies (mAb) are among the most promising biologic drugs currently on the market. They offer huge development potential due to their ability to safely target almost any type of cell surface or secreted molecule. The selectivity and specificity of mAbs resulted in the first generation of targeted therapies. They are now being used to treat a variety of diseases, including cancers, rheumatoid arthritis, Crohn's disease and other life-threatening conditions.

One of the first examples of precision medicine using a mAb was Herceptin®, (trastuzumab), a genetically engineered humanised mAb from Genentech, which was approved by the US Food and Drug Administration (FDA) in 1998 for the treatment of breast and gastric cancers that overexpress HER2. At about the same time, FDA also granted approval to Dako Corporation’s HercepTest®, an in vitro assay capable of detecting HER2 protein overexpression, which would allow physicians to identify patients who could benefit from trastuzumab.

Since the initial approval, there have been 19 updates to trastuzumab’s labelling information, with indications evolving to include adjuvant therapy for breast cancer, and most recently, the treatment of metastatic gastric cancer. The approval of trastuzumab also provided a foundation for the development of new drugs associated with HER2 receptor binding, including Perjeta® (pertuzumab), and Kadcyla® (ado-trastuzumab emtansine) for the treatment of HER2 positive breast cancer.

In the EU, trastuzumab was recently approved as a neo-adjuvant treatment in combination with pertuzumab for breast cancer. Although not approved for this indication in the US, it is possible that the FDA may consider this indication going forward. Pertuzumab has also been launched in multiple countries in combination with trastuzumab and docetaxel.

Though trastuzumab’s patent is now nearing its US expiration date, in 2019, which means biosimilar treatments are expected to become available in this region soon.

Patent expiry changes the game

Biosimilar versions of trastuzumab are currently being developed as lower-cost alternative treatments, with the goal of offering the same therapeutic benefits as the originator product. Multiple companies are developing or have already developed trastuzumab biosimilars, and at least three have been approved in other countries. Genentech’s overall trastuzumab franchise is projected to lose up to 45% of its worldwide sales with the introduction of biosimilars, though it is still likely to generate significant sales for several reasons:

Even with the advent of biosimilars, the use of trastuzumab is expected to continue after patent expiry due to its demonstrated ability to increase survival in HER2-positive breast cancer patients, its strong marketplace performance, and its link to pertuzumab as a neoadjuvant treatment. These current approvals ensure that trastuzumab’s medical use will continue even after patent expiry in these regions, and that its use in combination with other therapies could even grow.

However, these benefits are not guaranteed in perpetuity. Going forward, further demand for less expensive and better performing tests to identify patients who will benefit from the use of trastuzumab (including use with pertuzumab) is likely to evolve the companion diagnostic armamentarium. Within five years, we anticipate that trastuzumab in the EU and US will share a market with several biosimilars, allowing patients to benefit from an interchangeable treatment option at reduced cost. We should expect a pipeline of biosimilars-in-development for pertuzumab as well. New breakthrough therapies addressing covered indications could diminish the market opportunity for the current generation of anti-HER2 therapies and undercut the impetus for associated biosimilar development. As such, the development of biosimilars will become increasingly competitive.

Sponsors who want to stay ahead of this trend by developing the most competitive biosimilar product in terms of price and availability, should invest their resources in clinical and regulatory intelligence research on the reference product, and should invest their capital in the development of the best quality product, manufactured with the most efficient process.

Topics in this blog post: Biosimilars, Oncology, Commercialization
About The Authors

Vice President Strategic Drug Development, Head, Biosimilar Center of Excellence

Recent thinking: Biosimilars or biobetters?

Vice President, Global Strategic Drug Development and Head of Global Biosimilars Strategic Planning

Recent thinking: Biosimilars or biobetters?