Doctor explaining diagnosis to her female patient

Samsung Bioepis, a joint venture of Samsung Biologics and Biogen, and Merck & Co (known as MSD outside the United States and Canada) have confirmed that their version of trastuzumab (trastuzumab-dttb; Ontruzant®), a biosimilar of the reference biologic medicine branded as Herceptin® (Genentech/Roche)[1] is now available in the United States.

The reference drug Herceptin®, a recombinant DNA-derived humanized monoclonal antibody for use in the treatment of Human Epidermal growth factor Receptor 2-positive (HER2+) breast cancer and HER2+ gastric cancer, was developed by Genentech/Roche and is a standard of care therapy, representing a multibillion-dollar drug product.  The reference drug was  originally approved in 1998.

Samsung Bioepis’ biosimilar trastuzumab is the company’s first oncology biosimilar available in the United States.

The launch follows the approval from the United Stated Food and Drug Administration (FDA) in January 2019 for the 150 mg vial and in March 2020 for the 420 mg vial, based on Samsung Bioepis’ comprehensive data package, including analytical, nonclinical and clinical pharmacokinetics, safety and effectiveness data demonstrating that the biosimilar trastuzumab-dttb is highly similar to its reference product trastuzumab, and there are no clinically meaningful differences in terms of the safety, purity, and potency of the product.[2][3][4][5][6][7]

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“The launch of [this biosimilar product] to deliver our first oncology biosimilar in the United States marks an important milestone for Samsung Bioepis, and more importantly, for the patients who are in need of this proven treatment,” said Christopher Ko, President, and Chief Executive Officer, Samsung Bioepis.

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“While we understand that this is an unprecedented time for our hospitals and healthcare workers, we at Samsung Bioepis remain steadfastly committed to the patients we serve through our efforts to ensure the continued supply of our medicines through collaboration with our manufacturing and commercial partners,” he continued.

Indication and costs
Trastuzumab-dttb is indicated for the treatment of HER2-overexpressing breast cancer, metastatic breast cancer, and metastatic gastric cancer or gastroesophageal junction adenocarcinoma.

The drug will be introduced in the United States at a list price (wholesaler acquisition cost) of approximately U.S. $ 1,325.00 for the 150 mg single-dose vial and U.S. $ 3,709.00 for the 420 mg multiple-dose vial (prices are rounded), representing a 15% discount to the current list price of the reference drug. Wholesaler acquisition costs do not include discounts to payors, providers, distributors, and other purchasing organizations.

Agreement
Under the terms of the agreement between the partners, Samsung Bioepis will be responsible for preclinical and clinical development, process development and manufacturing, clinical trials and regulatory registration. Merck is responsible for commercialization activities for products approved in its partnered territories, including the US.

Samsung Bioepis’ trastuzumab biosimilar will be marketed and distributed in the United States by Merck. Earlier this year Merck announced that it intends to spin-off its women’s Health, trusted Legacy Brands and Biosimilars businesses, including Samsung Bioepis’ biosimilar, into a new, independent, publicly-traded company.

Merck confirmed that the company continues to fully support the commercialization of trastuzumab-dttb until the spinoff, which is intended to take place in the first half of 2021.

Under terms of the agreement, Samsung Bioepis is responsible for preclinical and clinical development, process development and manufacturing, clinical trials and regulatory registration while Merck is responsible for commercialization activities for products approved in its partnered territories, including the US.

Increasingly crowded marketplace
Biosimilar competition has been introduced to significantly reduce the financial burden of biologic treatments on the healthcare system in the United States.

Following the adoption of the Biologics Price Competition and Innovation Act (BPCIA) in 2009, which was designed to stimulate competition between pharmaceutical companies to develop less expensive biosimilar medicines, the FDA has created a shorter, less expensive approval pathway for equivalent treatments. As a result, a large number of highly similar biologic agents are being developed. These biosimilars are produced using the same amino acid sequence as the reference biologic, have the same mechanism of action, and are proven to have no clinically meaningful differences from its reference biologic in safety, potency, and purity. [8][9][10][11][12]

In addition to Samsung Bioepis’ trastuzumab biosimilar, there are no multiple FDA-approved biosimilar versions of trastuzumab on the market while others are being developed or are pending regular approval:

  • Ogivri® (trastuzumab-dkst; Mylan and Biocon) was approved in December of 2017 for treatment of patients with HER2-overexpressing breast or metastatic stomach cancers;
  • Herzuma® (trastuzumab-pkrb; Celltrion and Teva) was approved in December of 2018 with a limited indication for HER2-overexpressing breast cancer in adjuvant and metastatic settings;
  • Ontruzant® (trastuzumab-dttb; Samsung Bioepis and Merck & Co), was originally approved in January 2019 and shares all indications the original reference drug (Herceptin®);
  • Trazimera® (trastuzumab-qyyp; Pfizer) was approved in March 2019 and shares the same indications as to the original reference drug (Herceptin®);
  • Kanjinti™, originally known as ABP 980 (trastuzumab-anns; Amgen and Allergan) was originally approved in October 2019.
  • Taiwan-based Tanvex Biopharma is developing a trastuzumab biosimilar (TX-05). The proposed agent is currently in Phase III clinical development (NCT03556358)

Clinical trails
Efficacy and Safety Study of ABP 980 Compared With Trastuzumab in Women With HER2-positive Early Breast Cancer (Lilac) – NCT01901146
Trial to Compare the Safety, Efficacy, and Immunogenicity of TX05 With Herceptin® in HER2+ Early Breast Cancer NCT03556358
Extension Study to Provide Adjuvant Treatment Following Neoadjuvant Treatment and Surgical Resection in Protocol TX05-03 – NCT04109391

References/notes
[1] HERCEPTIN® package insert (Genentech/Roche).
[2] Paek K, Kim GW, Ahn SY, Lim JH, Jung D, Kim S, Lee JH. (2019). Assessment of the Molecular Mechanism of Action of SB3, a Trastuzumab Biosimilar. BioDrugs 2019 Dec;33(6):661-671.
[3] Lee JH, Paek K, Moon JH, Ham S, Song J, Kim S. Biological Characterization of SB3, a Trastuzumab Biosimilar, and the Influence of Changes in Reference Product Characteristics on the Similarity Assessment. BioDrugs (2019) 33:411-422.
[4] Lee JH, Paek K, Kim E, Kim I, Jeong J, Kim S. Comparison of in vitro antitumor activity between SB3 (trastuzumab biosimilar, Ontruzant) and Herceptin combined with an antibody for subdomain II of HER2 in HER2-positive cancer cells. J Clin Oncol. 2019 37:15_suppl, e14001-e14001.
[5] Pivot et al. A Randomized Phase I Pharmacokinetic Study Comparing Biosimilar Candidate SB3 and Trastuzumab in Healthy Male Subjects. Clin Ther. 2016 Jul;38(7):1665-1673.
[6] Pivot et al. Phase III, Randomized, Double-Blind Study Comparing the Efficacy, Safety, and Immunogenicity of SB3 (Trastuzumab Biosimilar) and Reference Trastuzumab in Patients Treated With Neoadjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer. J Clin Oncol. 2018 Apr 1;36(10):968-974.
[7] Pivot et al. A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: Final safety, immunogenicity and survival results. Eur J Cancer. 2018 Apr;93:19-27.
[8] Blackstone EA, Fuhr JP Jr. The economics of biosimilars. Am Health Drug Benefits. 2013;6(8):469-478.
[9] Cohen SB, Alonso-Ruiz A, Klimiuk PA, et al. Similar efficacy, safety, and immunogenicity of adalimumab biosimilar BI 695501 and Humira reference product in patients with moderately to severely active rheumatoid arthritis: results from the phase III randomized VOLTAIRE-RA equivalence study. Ann Rheum Dis. 2018;77:914-921.
[10] Rugo HS, Linton KM, Cervi P, Rosenberg JA, Jacobs I. A clinician’s guide to biosimilars in oncology. Cancer Treat Rev. 2016;46:73-79.
[11] Mulcahy AW, Hlavka JP, Case SR. Biosimilar cost savings in the United States: initial experience and future potential. RAND Corporation. https://www.rand.org/pubs/perspectives/PE264.html. Accessed January 5, 2018.
[12] Ryan AM. Frontiers in nonclinical drug development: biosimilars. Vet Pathol. 2015;52(2):419-426.

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