In the last few years, five new biosimilar versions of trastuzumab (Herceptin®) have been rigorously tested and approved by the FDA, although patent issues with the originator initially halted their market launch. With so many options becoming available, widespread adoption of trastuzumab biosimilars may depend on healthcare providers’ degree of comfort with evidence for their safety and efficacy.
Trastuzumab (Herceptin®) is approved in the USA for the treatment of early-stage and metastatic breast cancer overexpressing HER2. However, its high cost – at least $70,000 per year – can be a barrier to patient access. Due to their abbreviated approval processes, biosimilars including trastuzumab can potentially enter healthcare markets at lower cost than the original drug; hence biosimilar trastuzumab may provide patients an opportunity for expanded utilisation of this therapy.
Based on supporting evidence for their structural and functional similarity, equivalent pharmacological properties and efficacy versus originator product, the US FDA has approved five trastuzumab biosimilars for use in multiple indications to-date. The first of these biosimilars, named trastuzumab-tkst (Ogivri®), was evaluated clinically in a phase 3 trial in HER2+ metastatic breast cancer. This biosimilar, in combination with chemotherapy, was associated with a 69.9% overall response rate (ORR) compared with 64% for trastuzumab. Trastuzumab-tkst was FDA approved in 2017. Subsequently, four more trastuzumab biosimilars – namely trastuzumab-pkrb (Herzuma®; approved 2018), trastuzumab-dttb (Ontruzant®; 2019), trastuzumab-qyyp (Trazimera®; 2019), and trastuzumab-anns (Kanjinti®; 2019) – were assessed in phase III trials, all in the setting of HER2+ breast cancer, and demonstrated equivalent response rates and survival endpoints to those elicited by originator trastuzumab. Moreover, similar rates of adverse events were seen for biosimilar and trastuzumab groups in all studies.
Misconceptions on the level of evidence for biosimilars may pose a barrier to the utilisation of these drugs. Probably the most unfamiliar concept in the approval process for biosimilars is extrapolation of indications for which the originator biologic, but not the biosimilar, has been studied. However, scientific evidence to justify extrapolation based on biosimilarity is available for all approved products. Trastuzumab’s safety and efficacy are established for early-stage and metastatic breast cancer and metastatic gastric cancer. Based on the overall totality of evidence for trastuzumab biosimilars, they were also approved for the same indications. Uptake of these biosimilars will likely be proportionate with the level of confidence they inspire.
Key takeaway
Trastuzumab biosimilars have been approved based on the totality of evidence demonstrating biosimilarity to the reference product. Biosimilar uptake will be proportionate with the level of confidence inspired depending upon education of biosimilar efficacy and safety.
Anaemia is a common complication of chemotherapy in cancer patients. Biosimilar epoetins can restore haemoglobin (Hb) levels, reduce fatigue, and alleviate the necessity of blood transfusions for these individuals.
Chemotherapy-induced anaemia (CIA) is an undesirable consequence of myelosuppressive chemotherapy across a large range of cancer types and is independently associated with reduced survival. However, supportive therapy leading to a successful increase in Hb response can alleviate fatigue and improve quality of life (QoL) in patients with CIA. Erythropoiesis-stimulating agents (ESAs) such as epoetins are biologics used for a sustained correction of anaemia and the resultant improvement in QoL. This real-world, observational, post-marketing surveillance study aimed to observe Hb response/normalisation in CIA patients with solid tumours, lymphoma, or myeloma treated with once-weekly subcutaneous doses of biosimilar epoetin.
Findings
Among 2333 patients enrolled at over 200 participating centres, more than 80% of patients responded within 3 months of starting epoetin biosimilar therapy and nearly 90% of patients responded within 6 months of starting treatment. Similar results were observed for patients with solid tumours, including breast and lung cancer and hematologic malignancies. In responders, the mean time to achievement of target Hb was 80 days. Overall, 17% of patients experienced at least one adverse event, including rare cases of thromboembolism. Antithrombotic agents were required by 12% of patients. No unexpected treatment-related adverse events were identified.
Although ESA biosimilars are known to provide cost-efficiency in the management of CIA, physicians should not be obliged to prescribe biosimilar epoetin for purely cost reasons. This observational study under clinical conditions adds to the body of evidence supporting the safety and efficacy of biosimilar ESA epoetin in patients with CIA.
Key takeaway
Epoetin biosimilars have facilitated an increase in many patients’ QoL via an increase in levels of Hb within 3-6 months of starting therapy. This observational study, conducted under clinical conditions, supports the safety and efficacy of epoetin biosimilar prescription.
Although licensed biosimilars are subject to rigorous regulation frameworks and close post-marketing surveillance, they are still underused in the real-world setting.
Biologics account for half the pharmacological market in oncology; however, their main drawback is their high cost. Biosimilars were developed as cheaper alternatives with the dual aims of facilitating access to novel treatments and reducing healthcare expenditures.
Biosimilars are defined by the US FDA and European Medicines Agency as highly similar biological products with no clinically meaningful differences to an existing approved reference product in terms of safety, purity, and potency. Because biosimilars are not identical to their reference biologic, biosimilarity must be demonstrated by evidence from pharmacokinetic and pharmacodynamic studies. Despite the stringent requirements for reliable scientific data and successful clinical trials for all approved biosimilars, knowledge concerning these drugs is lacking – with one quarter of oncologists reportedly able to describe a biosimilar, and one fifth of prescribers familiar with the concept.
As patents for biologics expire, more biosimilars are set to enter the oncology drugs market. The main concern of cancer clinicians over the use of biosimilars is risk of immunogenicity, as even minor differences in molecular structure, impurities, route of administration, and storage conditions between these drugs and reference products could potentially incur adverse effects. Ongoing pharmacovigilance and post-marketing safety monitoring activities – which are mandatory for all approved biologics and biosimilars – should help to dispel these worries over the long term.
Biosimilars represent significant cost savings to healthcare systems. It has been calculated that a 20% reduction in the price of six off-patent biologics would create savings of billions of euros, which when spread out would enable patients access to more treatments. However, these price forecasts also depend on the cost of reference biologics and the competition market.
For patients with cancer, biosimilars are more affordable drugs with a similar safety and toxicity profile and no clinically meaningful difference compared with their reference biologics. Current underuse of biosimilars may be attributed to lack of awareness among patients and clinicians of the benefits and challenges of these important medications. Healthcare professionals, and the public alike, should be properly educated on multiple aspects of biosimilars to ensure their successful incorporation in routine oncology care.
Key takeaway
Healthcare practitioner knowledge concerning biosimilars is lacking. There needs to be greater educational opportunities covering all aspects of biosimilar safety and efficacy to ensure successful incorporation of biosimilars in routine oncology care.
The testing and approval pathway for ABP 980 provides a model of accelerated development programs for novel, safe, and efficacious biosimilars.
There is increasing interest in biosimilars as alternatives to their originator reference product (RP), given their potential to improve patient access to important biological treatments. ABP 980 is a biosimilar of trastuzumab (Herceptin). Like trastuzumab, ABP 980 exerts its therapeutic effects by targeting cancer cells that overexpress the HER2 receptor, including those of the breast and stomach. ABP 980 is approved in the EU, USA, and Japan for the same indications, dosages, and route of administration as trastuzumab RP.
During development, ABP 980 underwent comprehensive analytical characterisation using state-of-the-art techniques. These assessments demonstrated ABP 980 has highly similar structural and functional attributes to trastuzumab RP, with only minor differences that are not expected to alter its biological activity or clinical performance. Phase I pharmacology studies conducted in healthy subjects confirmed ABP 980 has equivalent pharmacokinetics properties relative to trastuzumab RP.
Clinical similarity was evaluated in the LILAC study in women with HER2+ early breast cancer – who were deemed a sensitive patient population. The primary endpoint, pathologic complete response, was noted in 48% of patients treated with ABP 980 and 41% of those receiving trastuzumab RP – demonstrating noninferiority between the two groups. The trial confirmed clinical similarity between ABP 980 and trastuzumab RP. Safety and immunogenicity of the two test products were also similar. On the basis that the drug’s mechanism of action – inhibition of HER2-mediated proliferation – is the same for different cancer cells, the totality of evidence for ABP 980 supported scientific justification for extrapolation across all approved indications for trastuzumab RP. ABP 980 provides an additional treatment option for patients with breast and gastric cancers.
Key takeaway
The biosimilar, ABP 980, shows similar structural and functional attributes, as well as demonstrating clinical non-inferiority in a clinical trial, when compared to its trastuzumab RP. This provides an additional treatment for breast and gastric cancer therapy, and therefore improving patient access.