Hope Rugo, MD
Since 2006, the European Medicines Agency has granted marketing authorization for more than 40 biosimilars, and, in less than 4 years, the FDA has approved 17,1,2
yet the knowledge gap in the understanding of biosimilarity poses a unique challenge to the agents’ assimilation into clinical practice and possible impact on access and cost savings, experts say.
Hope S. Rugo, MD, FASCO, a program cochair for the 36th Annual
Miami Breast Cancer Conference®
(MBCC), has been a leader in the effort to develop biosimilar versions of trastuzumab (Herceptin), the monoclonal antibody that has helped transform care for patients with HER2-positive breast cancer. The FDA has now approved 3 trastuzumab biosomilars: trastuzumab-dkst (MYL-1401O; Ogivri), trastuzumab-pkrb (CT-P6; Herzuma), and trastuzumab-dttb (SB3; Ontruzant) (Table
During a presentation Friday at MBCC, Rugo discussed how regulatory agencies evaluate proposed trastuzumab biosimilars, along with key issues such as whether biosimilars should extrapolate the same indications as the reference product and whether they should be interchangeable.
“Biosimilars are biologic agents that are highly similar to an approved biologic product, referred to as the reference product. Based on analytic, pharmacokinetic, pharmacodynamic, and clinical trial data, there are no clinically meaningful differences in terms of quality, safety, and effectiveness from the reference product,” Rugo said in an email interview in advance of her presentation. “As effective biologic agents go off patent in the United States and Europe, biosimilars have the potential to markedly reduce the cost of healthcare and improve access for patients who can benefit from these agents.”
Rugo, a professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, noted that supportive care medications such as filgrastim are being used routinely in clinical practice.
The first biosimilar versions of trastuzumab could enter the US market during the second half of 2019, according to Roche, which holds the patents on the drug.3
The introduction of biosimilars in other countries has resulted in lower prices for the reference product, according to Rugo.
“Biosimilars are here to stay,” Rugo said in a previous interview with OncLive®
. “They’re being used in Europe and the rest of the world. They will come to the United States. My biggest hope for biosimilars is that they’ll improve access to lifesaving therapy.”
Although the FDA has established extensive criteria to evaluate a potential biosimilar, myths about these products persist, Rugo and colleagues wrote in an article in Future Oncology
These include inaccurate perceptions that less clinical and nonclinical evidence is required for their approval, that there are differences in the primary structure between a biosimilar and a reference product, and that biosimilars must have clinical data for each indication to gain approval in that setting.4
In fact, regulatory approval is based on a “‘totality of evidence” substantiated by structural and functional classification, nonclinical evaluation, assessment of clinical pharmacokinetics and immunogenicity, and comparative clinical efficacy and safety data. For approval, biosimilars must demonstrate similarity with the reference drug “in terms of quality characteristics, biological activity, safety, and efficacy,” according to Rugo and colleagues.4
“As increasing numbers of biosimilars achieve regulatory approval and are available for use in clinical practice, it is important for the medical community to understand the underlying concepts behind the evaluation of similarity and the approval of biosimilars for use in clinical settings,” the authors said.4
Efficacy Data Present for Approvals
In December 2017, MYL-1401O became the first trastuzumab biosimilar to receive FDA approval. Codeveloped by Mylan and Biocon, the biosimilar is indicated in similar settings as trastuzumab: HER2-positive patients with breast cancer or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
The approval was based on structural and functional product comparisons, animal data, human pharmacokinetic and pharmacodynamic data, and clinical studies including clinical immunogenicity, the FDA said in announcing the approval.5