Breast cancer treatment was primarily based on the tumor’s location for most of the previous century, resulting in varying outcomes. Patients with metastatic HER2+ breast cancer would typically undergo conventional chemotherapy until the availability of trastuzumab, a breakthrough therapy. In September 1998, the FDA approved HERCEPTIN, a breast cancer treatment developed by Roche and Genentech, as adjuvant therapy for HER2-positive node-positive breast cancer. This treatment regimen included doxorubicin, cyclophosphamide, and paclitaxel. Subsequently, HERCEPTIN received approval for metastatic HER2-positive breast cancer from European authorities in 2000 and the Japanese Ministry of Health, Labor and Welfare in 2001.
The approval of HERCEPTIN represented a significant milestone in the treatment of HER2+ breast cancer. It was the first targeted therapy specifically designed for a solid tumor and also the first medication to be used alongside a companion diagnostic. By identifying patients with a higher likelihood of benefiting from the treatment, HERCEPTIN provided these individuals with the crucial time that would have otherwise been spent searching for a suitable treatment option.
Herceptin’s Breakthrough in Adjuvant Treatment
The approval of HERCEPTIN for HER2+ breast cancer was a significant milestone in targeted cancer therapy, but further advancements followed. In 2006, HERCEPTIN received FDA approval for adjuvant treatment of HER2-positive breast cancer, demonstrating a 50% reduction in the risk of relapse and a 33% decrease in the risk of death. These groundbreaking studies had a transformative impact on the lives of HER2-positive breast cancer patients. HERCEPTIN became the sole approved targeted biological therapy for HER2-positive breast cancer, both in adjuvant and metastatic settings.
Subsequently, pertuzumab was approved in 2017 for HER2+ breast cancer adjuvant treatment, but it was used in combination with trastuzumab. Despite the introduction of the trastuzumab and pertuzumab combination, HERCEPTIN still maintained a significant market share in the adjuvant setting, although the launch of the combination therapy shifted the market dynamics towards PHESGO. Nonetheless, HERCEPTIN’s position was protected against biosimilars.
HERCEPTIN’s Revenue Plunge: The Biosimilar Onslaught Shakes the Breast Cancer Market
Following the introduction of biosimilar versions of HERCEPTIN in numerous countries, combined with price and volume fluctuations, HERCEPTIN experienced a continuous decline in sales. The price of the first HERCEPTIN biosimilar in 2019 was 15% lower than the original drug, and by 2022, the price of the fifth biosimilar had dropped by 58% compared to the 2019 price of HERCEPTIN. As a result, HERCEPTIN’s cost decreased from a peak of ~USD 90,000 in 2019 to USD 64,000 in 2022, a 29% reduction. The average cost of biosimilar treatments, when unweighted, was 40% lower than HERCEPTIN, amounting to USD 38,000. In 2022, HERCEPTIN generated approximately USD 2 billion in global sales, experiencing a decline of 19% globally and 28%, 17%, and 28% in the US, EU, and Japan, respectively.
HERCEPTIN SC vs. Biosimilars: The Battle for Breast Cancer Treatment Dominance
While the first biosimilar of HERCEPTIN entered the US market in July 2019, Europe and Japan had their first biosimilar launches in March 2018 and November 2018, respectively. However, Roche did not remain passive in the face of increasing physician awareness and confidence in biosimilars. The company took an active approach to potentially counter biosimilar competition by introducing a novel subcutaneous (SC) formulation of HERCEPTIN in the EU in 2013 and in the US in 2019. All approved HERCEPTIN biosimilars (KANJINTI, OGIVRI, TRAZIMERA, HERZUMA, and ONTRUZANT) were limited to intravenous (IV) infusion administration, which typically took 60-90 minutes, while HERCEPTIN SC required only 2-5 minutes for administration.
According to the prefHER study, which revealed that 86% of patients chose SC dosing, the availability of HERCEPTIN SC gave patients a preferred substitute to biosimilar medicines. Roche does not anticipate that HERCEPTIN SC will gain a sizable market share in the US due to the well-established preference for IV dosage. Because trastuzumab is frequently provided simultaneously with another IV medication and many patients already have a central venous line in situ, the SC formulation may not provide patients with any additional convenience in the adjuvant setting.
Because there is no longer a requirement for a second injection, IV administration might be more practical. Trastuzumab biosimilars are more affordable than the SC even though the price of HERCEPTIN IV is higher owing to a longer chair time and hospital costs. This affordability factor may improve access by providing physicians with a lower-cost option to prescribe. Notably, there has been a substantial decline in HERCEPTIN sales in the US.
PERJETA: Roche’s Marvel in HER2 Biologics – Empowering Breast Cancer Treatment to New Heights
With the release of PERJETA, KADCYLA, and PHESGO, Roche expanded their HER2 franchise. As an addition to Roche’s popular medicine HERCEPTIN, PERJETA was created with the goal of extending the shelf life of its top-selling pharmaceuticals. FDA approval came in June 2012, followed by EMA approval in March 2013, and Japan clearance in August 2013. In order to give a synergistic impact against HER2-positive tumors, PERJETA was created to be used in conjunction with HERCEPTIN, targeting various HER2 receptor areas.
Roche’s PERJETA has become another promising oncology medication, with strong sales growth in every area. Its sustained success was further aided by the rising demand for PERJETA in adjuvant early breast cancer therapy. In 2020, 2021, and 2022, PERJETA generated global sales of approximately USD 3.7 billion, 4 billion, and 4.4 billion, respectively.
PHESGO: Roche’s Breakthrough in Breast Cancer Treatment – Defending Against Imitators and Igniting Expansion
Roche released PHESGO, a fixed-dose combination of HERCEPTIN and PERJETA for early and metastatic HER2-positive breast cancer patients, to guard against HERCEPTIN copycat goods. PHESGO is a single-dose medication that can be used at treatment facilities or even at home. It is delivered subcutaneously along with intravenous chemotherapy. Each subsequent treatment requires about 5 minutes after an initial loading dosage of 8 minutes.
Since its debut, PHESGO has seen a sharp increase in sales, especially in Europe and the US, with revenues expected to reach over USD 350 million in 2021 and USD 780 million in 2022. 80% of breast cancer patients in the UK are now using PHESGO, which reduces the need for IV infusions and frees up hospital space. Chugai, a member of the Roche Group, has also applied for regulatory clearance of PHESGO in Japan, opening up yet another potential path for further development. Roche’s HER2 franchise sales, which also include PERJETA, HERCEPTIN, KADCYLA, and PHESGO, increased internationally by almost 3% to reach USD 9.5 billion.
However, Roche may encounter difficulties from PERJETA and KADCYLA biosimilars that will soon be available, as well as rivalry from HERCEPTIN biosimilars. The competitive environment for treating metastatic breast cancer has become more intense with the introduction of additional drugs including MacroGenics’ MARGENZA and Seagen’s and Novartis’ tyrosine kinase inhibitors.
