Type: Abstract Library

A selection of evidence-based and peer-reviewed literature to expand your learnings on biosimilars and increase your confidence of their use in clinical practice

Healthcare professionals’ trust in biosimilars is key to ensuring their availability

Given the high cost and sharply increased use of biologics in recent years, the approval pathway for biosimilars echoes a phenomenon first introduced for generic drugs 40 years ago

Since the simplest forms of biologics (blood products and vaccines) entered the US market in the 1970s, followed by recombinant human insulin in 1982, and the first FDA-approved monoclonal antibody in 1997, biologics have transformed the treatment of serious medical conditions, but have also sharply increased the overall healthcare cost curve.

In 2009, the Biologic Price Competition and Innovation (BPCI) Act was passed to create an avenue for abbreviated FDA licensure pathways for biosimilars, and thereby enable developers to bring them to market at the lowest viable cost. The first biosimilar, filgrastim-sndz, was approved in the USA in 2015 and was quickly followed by many more approvals of biosimilars for an array of medical conditions.

Biosimilars are manufactured following reverse-engineering – by starting with the final therapeutic protein and working the synthesis steps backwards. Like all biologics, biosimilars are created in living systems (cell lines), and therefore are not exact copies of their reference product, although they are required to have the same amino acid sequence. During the development and approval process, their small molecular differences must be demonstrated not to impact efficacy and safety (i.e. not to be ‘clinically meaningful’). Because of this, the approval pathway for biosimilars is largely focused on analytical studies of their physical characteristics relative to the originator product, albeit supplemented with clinical evaluation.

Biosimilars are not granted patent exclusivity – several biosimilar versions of the same reference product may be available to purchase. For example, there are six FDA-approved biosimilars of trastuzumab. As more of these products enter the market, there will be increasing need for healthcare providers to gain trust in their efficacy and safety. With ever-rising healthcare costs and biologics occupying the most expensive drug category, the advent of high-value biosimilars may serve as a release valve to otherwise unsustainable markets. Healthcare professionals need to stay committed to evaluating biosimilar evidence to make these treatment options available.

Key takeaway

Biosimilars are not granted exclusivity on approval and there may be several biosimilars for a single biologic. Healthcare providers need to gain trust in the efficacy and safety of each biosimilar that is marketed; although greater numbers of high-value biosimilars will help reduce overall healthcare costs.

Biosimilar trastuzumab cuts an expensive obstacle to effective treatment for many women with HER2+ breast cancer

The extensive preclinical and clinical testing program for CT-P6 demonstrates this biosimilar is as safe and effective as reference trastuzumab, and its clinical use could considerably reduce financial toxicity without compromising care.

The development of trastuzumab monoclonal antibody in the 1990s was a milestone in targeted therapy that has dramatically improved progression-free and overall survival rate in patients with breast cancer overexpressing the HER2 receptor (which account for 15% of all breast cancer diagnoses).

The success of trastuzumab opened the floodgates for a new generation of targeted therapies for both early-stage and metastatic breast cancer and other solid tumours – although at a huge financial burden. Biosimilars were developed in response to this problem. CT-P6 (trastuzumab-pkrb, Herzuma) is a trastuzumab biosimilar currently approved in the EU, Japan, South Korea, Australia, and USA. Like all biosimilars, CT-P6 underwent rigorous testing during pre-approval stage. In head-to-head comparisons CT-P6 demonstrated equivalent pharmacokinetics parameters, adverse events profile, immunogenicity level and anti-cancer efficacy compared with reference trastuzumab. Clinical trials have been conducted in women with stage I–IIIa operable HER2-positive breast cancer. These trials revealed that neoadjuvant CT-P6 added to chemotherapy does not elicit a significantly different pathologic complete response rate to the same treatment approach using the reference, trastuzumab.

In all, the totality of evidence for CT-P6 supports its biosimilarity to the reference, trastuzumab. CT-P6 can be safely used in patients with HER2-positive breast cancer and other malignancies where indicated. Rapid integration of economically favourable biosimilars such as CT-P6 promises to improve access to essential medicines and help alleviate overburdened healthcare systems.

Key takeaway

The development of the trastuzumab biologic dramatically improved outcomes for a large proportion of HER2-overexpression breast-cancer patients, although the financial burden has been high. The trastuzumab biosimilar, CT-P6, shows comparable pharmacokinetic parameters and anti-cancer efficacy compared to the reference biologic, and with lower associated costs, makes it economically favourable to healthcare providers.

Houston comprehensive cancer centre develops a standardised approach to evaluate and implement biosimilar products

Abstract published: August 2021
Development of a standardised approach for evaluating and assimilating biosimilars should improve efficiency of their integration into existing workflows. A comprehensive cancer centre shares some practical considerations to serve as a guide to other institutions as they navigate the biosimilars landscape and support the transition to biosimilars in practice.

Biosimilars – biological products that are highly similar to reference products with no clinically meaningful differences – were allowed to enter the US market following ratification of the Biologics Price Competition and Innovation Act. Access to these potentially cheaper drugs was anticipated to reduce total pharmaceutical expenditures in the USA ranging between $24 and $150 billion within a 10-year period, with a corresponding reduction in total spending on biologics of approximately 3%. However, biosimilars still comprise less than one third of the total biologics use.

For cancer patients, providers seem more amenable to use biosimilars in the settings of palliation and supportive care than for curative purposes. Barriers to more widespread use of oncology biosimilars may include prescribers’ concerns over safety and efficacy, pricing and contract issues, and laws and regulations for substitution and interchangeability. These barriers may be effectively overcome by better prescriber education on switching studies, clear FDA guidance on substitution, and reform of formulary policies. And from a practical standpoint, willingness to provide temporal and financial investment to operationalize transition to biosimilars is required.

For the above reasons, a comprehensive cancer centre in Houston, TX reports the strategies, challenges, and lessons learned when they elected to move forward with biosimilars.

The first biosimilar evaluated for formulary addition at the cancer centre was the hematopoietic growth factor filgrastim-sndz. After a failed preliminary assessment, subsequent payer policy change and greater opportunities for cost savings, coinciding with publication of post-marketing safety data, led to re-evaluation and full implementation of the biosimilar alongside formulary deletion of the reference biologic. Formulary review for this process included the following steps – first, cost, coverage, and access were evaluated, followed by formulary preparation for use of the biosimilar with engagement of requesting physician, pharmacy, and therapeutics (P&T) committee, and purchasing personnel.

These experiences allowed the cancer centre to transition to biosimilar implementation within an effective timeline.

Key takeaway

Trastuzumab is the gold standard of treatment for HER2-expressing cancers, although it is associated with an iThere are many barriers to the increased use of oncology biosimilars in treatment: concerns over safety and efficacy, pricing and contract issues, and laws and regulations for substitution and interchangeability. Improved prescriber education on switching studies, clear FDA guidance on substitution, and reform of formulary policies may help to overcome these barriers and start the transition to biosimilar implementation.

Trastuzumab biosimilar ABP 980 is as safe as reference product in terms of cardiac toxicity in patients enrolled in the long-term LILAC study

Abstract published: August 2021
Cardiotoxicity is the most important limitation in the application of trastuzumab, and one of the most important parameters to monitor when assessing the safety of a trastuzumab biosimilar.

Trastuzumab (Herceptin®) is the gold standard of care for people with early and metastatic breast cancers and metastatic gastric cancer overexpressing human epidermal growth factor receptor 2 (HER2). The phase III LILAC trial demonstrated ABP 980 had biosimilarity to trastuzumab reference product (RP) in women with HER2-positive early breast cancer, with no clinically meaningful difference between the two products. Based on the totality of evidence, ABP 980 was approved by the European Medicines Agency (EMA), and subsequently by the FDA, for the same indications as trastuzumab RP.

Cardiac toxicity is a rare but serious concern with trastuzumab; possibly related to HER2 blockade. In the LILAC study, patients were randomized to receive neoadjuvant ABP 980 or trastuzumab RP for 4 cycles prior to surgical resection, and consolidation treatment with either drug given every 3 weeks for up to 1 year thereafter. To monitor cardiac safety, an electrocardiogram and 2-D echocardiogram were performed at all visits.

Overall, no marked decline of left ventricular ejection fraction (LVEF) was observed. In patients who received ABP 980 or trastuzumab RP throughout the study and those who were switched from trastuzumab RP to ABP 980 in the adjuvant (postoperative) phase, LVEF decline (10–50%) was seen in 2.8%, 3.3%, and 3.5% of patients, respectively. There were no meaningful differences between treatment arms. Moreover, incidence of cardiac failure was comparable among the three groups: 2.2%, 0.5%, and 1.2%, respectively. The majority of LVEF decline cases were asymptomatic, and most patients exhibiting LVEF decline during the 1-year study had pre-existing cardiovascular conditions at baseline, including hypertension and arrhythmias. Most cardiac failure reports were grade 1 or 2, although none were classified a serious adverse event.

The LILAC study revealed a low incidence of cardiac toxicity following 1-year treatment with trastuzumab biosimilar ABP 980, with no clinically meaningful difference in the rate of LVEF decline between treatment arms. Cardiotoxicity is the most important limitation in the application of trastuzumab. Hence the acceptable safety and tolerability profile observed in this study suggests ABP 980 may be a useful choice in patients starting treatment or when considering switching from trastuzumab RP.

Key takeaway

Trastuzumab is the gold standard of treatment for HER2-expressing cancers, although it is associated with an increased cardiac toxicity risk. The biosimilar, ABP980, demonstrated biosimilarity to the reference product, suggesting no increased risk from switching to the trastuzumab biosimilar.