Oncology Biosimilars Enter an Era of Expansion

Biological products are the fastest-growing class of pharmaceuticals in the United States. Biosimilar and interchangeable products may offer additional treatment options and potentially lower health care costs for patients requiring biological therapies. Since the first FDA-approved biosimilar in 2015, the list of approved biosimilars has grown to 31, with many more in the pipeline.^1,2

This growth is significant because it opens the door to competition in the market as well as expanded patient access to critical medication. Manufacturers have been successful in capturing significant market share by setting competitive biosimilar pricing and additional contracting.

With an aging population and growing need to treat chronic, complex conditions, specialty biologics are on the rise. In recent years, there has been an increased uptake of biosimilars, particularly in the oncology space. In an environment where health decisions are increasingly made on cost, biosimilars will play an important role in improving access to these types of medicines.

During the next decade, the launch of biosimilars could save consumers a significant amount of money. Furthermore, increased affordability may boost access to treatments for millions of patients who may otherwise have forgone or compromised for less effective treatments.

The Evolving Landscape of Biologics and Biosimilars in Oncology

Prescription drug spending per capita in the United States is more than double that of other high-income countries. Because of the development of biosimilars, savings in the United States over the next several years are projected to exceed $100 billion if use continues to increase.^1,3

Although the initial uptake of biosimilars in the United States was slower compared with that in other countries, more recent approvals have demonstrated a much faster uptake, especially with oncology biosimilar medications such as bevacizumab (Avastin; Genentech), trastuzumab (Herceptin; Genentech), and rituximab (Rituxan; Genentech) in particular. Prescribers are gaining familiarity with oncologic biosimilars, and the Centers for Medicare & Medicaid Services has established separate codes and payment rates for oncologic biosimilar agents to encourage their use.

Oncologic biosimilars have also launched with wholesale acquisition costs averaging 15% to 37% lower than for their reference products.¹ As more oncologic biosimilar agents enter the market, especially for those with more than 1 biosimilar entrant, not only are costs trending lower, but average sales prices (ASPs) for their reference products are decreasing too. This implies that manufacturers of the reference products may be offering additional rebates and contracting. Some examples of products in the oncology space with declining ASPs include bevacizumab, trastuzumab, rituximab, epoetin alfa (Procrit; Janssen Products, LP), and epoetin alfa (Epogen; Amgen).¹

The first FDA-approved biosimilar was an oncology supportive agent—the short-acting granulocyte colony-stimulating factor (G-CSF) filgrastim-sndz (Zarxio; Sandoz). Filgrastim-sndz has been available for 6 years and has gained approximately 72% of the filgrastim market. Pegfilgrastim biosimilars now have approximately 42% of the long-acting G-CSF market.¹

Of the oncologic biosimilars, bevacizumab products have secured approximately 37% of the market, trastuzumab products have an estimated 35%, and rituximab biosimilars have 17% to 20%.¹ Epoetin alfa-epbx (Retacrit; Pfizer Inc), another oncology supportive agent, has approximately 25% of the market for epoetin alfa versus 18% for Janssen’s epoetin alfa Procrit and 57% for Amgen’s epoetin alfa Epogen.¹

One issue with the launch of biosimilars was the potential for “skinny labeling” due to regulatory or patent issues, but not necessarily clinical concerns. A skinny label refers to a biosimilar’s prescribing information or label not including all the original reference product’s indications. For example, pegfilgrastim (Neulasta; Amgen) is indicated for hematopoietic subsyndrome of acute radiation syndrome, which the current FDA-approved biosimilar agents do not have in their labeling.

Skinny labeling may also be a tactic used by biosimilar manufacturers to expedite FDA approval of their product using the indications not covered under patent. With etanercept-szzs (Erelzi; Sandoz), for example, the therapy received FDA approval in 2016 but has been held up in court over patent disputes.⁴

Health systems, however, have not seemed as concerned with skinny labeling of biosimilars because no specific clinical issues have been raised as a result.

A biosimilar is a biological product that is considered both “highly similar” and to have “no clinically meaningful differences” compared to the reference product.⁵ However, pharmacists may not substitute biosimilar agents between each other or the reference product. A possible exception to this rule is products designated as “interchangeable,” which would have to meet additional requirements as outlined in the Biologics Price Competition and Innovation Act of 2009.

An interchangeable biosimilar is defined by the FDA as a product that is expected to produce the same clinical result as the reference product in any given patient.⁵ On a federal level, if the FDA approves a biosimilar as interchangeable, a pharmacist may substitute it for the reference product without prior approval from the prescriber, but pharmacy laws and practices vary from state to state, meaning that individual state pharmacy practice acts must also permit substitution.^5,6 Most states have also implemented some additional hurdles to overcome prior to dispensing an interchangeable biologic medication.⁶

Many health plans and health care systems have already implemented programs making biosimilars preferred agents, as well as using step therapy and criteria to encourage product switching. Although the FDA has released guidance on the interchangeability of biosimilars with reference products and manufacturers may now pursue this classification, there are currently no FDA-approved interchangeable products in the oncology landscape.

Oncologic Biosimilars in the Pipeline

In addition to the current FDA-approved oncology and oncology supportive biosimilars, a number of potential products are in the pipeline with launches planned for the near future. Growing evidence suggests increased utilization of biosimilars in oncology, and experts predict these additional products may continue to propel the use of biosimilar agents and maintain the opportunity for further savings.⁷

The oncologic biosimilars pipeline includes Genentech’s trastuzumab, which has 3 biosimilar candidates in phase 3 clinical trials for HER2-positive breast cancer: EG12014 (EirGenix, Inc/Sandoz), HD201 (Hanwha/ Prestige Biopharma Limited), and TX-05 (Tanvex BioPharma, Inc). Genentech’s rituximab also has 2 near-term biosimilar candidates in phase 3 for follicular lymphoma: DRL_RI (Dr Reddy’s Laboratories Limited) and MabionCD20 (Mabion SA).

Additionally, Genentech’s bevacizumab has 5 products pending approval for non–small cell lung cancer, colorectal cancer, and other cancers: FKB238 (Centus Biotherapeutics), SB8 (Organon & Co/Samsung Bioepis Co, Ltd), BAT1706 (Bio-Thera Solutions), Bmab-100 (Biocon Ltd/Mylan/Viatris), and BEVZ92 (Amneal Pharmaceuticals/Insud Pharma/mAbxience).

Currently, the oncology supportive pipeline candidates that are being assessed for patients with cancer receiving myelosuppressive chemotherapy and other indications include 7 biosimilars of Amgen’s pegfilgrastim and pegfilgrastim on-body injector (Neulasta Onpro): Lupifil-P (Lupin), Lapelga (Accord BioPharma/Apotex), MSB11455 (Dr Reddy’s Laboratories Limited/Fresenius Kabi), TPI-120 (Adello Biologics/AE Companies/Amneal/Kashiv BioSciences), Udenyca on-body injector (Coherus BioSciences, Inc), MSB11455 on-body injector (Fresenius Kabi), and Lupifil-P on-body injector (Lupin). For the same indications, Amgen’s filgrastim (Neupogen) also has 2 products pending approval: Filgrastim Kashiv (Adello Biologics/AE Companies/Amneal) and Grastofil (Accord BioPharma/Apotex).

Conclusion

As the demand for biologics continues to grow, there is an increasing anticipation surrounding the opportunity for less expensive biosimilars to play an important role in controlling overall drug spending. Analysts estimate biosimilars have the potential to save up to 3% of total biologic spending during the next 10 years.⁷

The United States has been slow to approve and adopt biosimilars. However, evidence shows increased utilization and a growing pipeline of products that may drive biosimilars' use and potentially yield significant cost savings.⁸ As evidenced by the rapid uptake of bevacizumab, trastuzumab, and rituximab biosimilar agents, the oncology space continues to be the most successful and competitive market for biosimilars to date.^1,7 The anticipated launch of additional oncology and oncology supportive agents in the near-term pipeline will hopefully mark just the beginning of the expanding era of biosimilars in the United States.

Rachel K. Anderson, PharmD, CSP, is a clinical program manager at AllianceRx Walgreens Prime.

References

1. IPD Analytics. Rx brief: update on biosimilars in the United States. November 5, 2020. Accessed November 23, 2021. https://www.ipdanalytics.com/

2. Biosimilar product Information. FDA. Updated December 27, 2021.
Accessed January 11, 2022. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information

3. FDA approves Samsung Bioepis and Biogen’s Byooviz (SB11), Lucentis biosimilar (ranibizumab-nuna). News release. Biogen Inc. September 20, 2021. Accessed November 23, 2021. https://investors.biogen.com/news-releases/news-release-details/ fda-approves-samsung-bioepis-and-biogens-byooviztm-sb11

4. Decker S. Amgen avoids Supreme Court review of patents on Enbrel drug. Bloom- berg. May 17, 2021. Accessed November 23, 2021. https://www.bloomberg.com/news/ articles/2021-05-17/amgen-ducks-supreme-court-review-of-patents-on-enbrel-drug

5. Franklin J. Biosimilar and interchangeable products: the US FDA perspective. FDA. 2018. Accessed November 23, 2021. https://www.fda.gov/media/112818/download

6. State laws for biosimilar interchangeability. Cardinal Health. July 2021. Accessed December 10, 2021. www.cardinalhealth.com/en/product-solutions/pharmaceutical products/biosimilars/state-regulations-for-biosimilar.html

7. Drug life-cycle insights across the globe. IPD Analytics. October 14, 2021. Accessed November 23, 2021. https://www.ipdanalytics.com/lifecycleinsights

8. Biomedtracker. Informa Pharma Intelligence. Accessed November 23, 2021. https:// www.biomedtracker.com