Emerging Trastuzumab Biosimilar May Promote Competition

Elisavet Paplomata, MD

Multiple trastuzumab (Herceptin) biosimilars are currently being developed in the United States. In the wake of the December 2017 approval of MYL-1401O (Ogivri; trastuzumab-dkst), Elisavet Paplomata, MD, believes that ABP 980 may be the next trastuzumab biosimilar to make it through the regulatory process in both the United States and Europe.

The European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion for the marketing authorization of ABP 980 in March 2018 based on data from the phase III LILAC study. This study compared neoadjuvant paclitaxel plus ABP 980 with neoadjuvant paclitaxel plus trastuzumab.

Findings from the LILAC trial showed that in women with HER2-positive early breast cancer, 47.8% of patients in the ABP 980 arm (n = 364) and 41.8% in trastuzumab arm (n = 361) achieved pathologic complete response (pCR), according to central independent review. Risk difference of pCR was 5.8% (90% CI, -0.5 to 12.0) and risk ratio of pCR was 1.14 (90% CI, 0.993-1.312).

Amgen and Allergan, the developers of ABP 980, also submitted a biologics license application for the biosimilar to the FDA in 2017.

The approval of this biosimilar would create competition with both the original biologic and MYL-1401O, which could drive down costs, said Paplomata. Additionally, international approval of this biosimilar could allow low-income countries to access treatment for their patients with HER2-positive breast cancer.

OncLive: There are multiple trastuzumab biosimilars in development, and one is approved in the United States. Can you provide insight on this evolving area?

In an interview with OncLive, Paplomata, assistant professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, discussed ABP 980 and the impact that biosimilars may have on global access to cancer care.Paplomata: Biosimilars are different than generic drugs, which we are all very familiar with. Generic drugs are structurally the same drug as the parent drug. A biosimilar is a biologic product which may have a similar but different structure from the reference product, but has shown in phase III trials to have the same efficacy and safety.

The FDA has a specific process of approving [these types of] drugs. Of course, they are cheaper than the parent drug to develop because they do not require all of the clinical trials that trastuzumab had to go through to be approved for all the indications. If a trial of a biosimilar shows the same efficacy as a reference product, it can be approved for all the same indications.

There are multiple biosimilars in development right now. The biosimilar industry did not start in oncology, but in inflammatory disorders like rheumatoid arthritis. Biosimilars have been used for several years in Europe. Even though we have not used biosimilars as anticancer therapy, we as oncologists have experience with another biosimilar—filgrastim-sndz (Zarxio), which is a biosimilar of filgrastim (Neupogen). That was approved in 2015, and we have used it for about 1 year now.

Some payers favor Zarxio, as it is about 15% cheaper than the parent drug. Many oncologists have encountered this in their practice. In this case, we inform the patient that we will use the specific drug instead based on their insurance coverage and we proceed with this alternative therapy. The efficacy and side effect profile are similar. My understanding is that Zarxio has not really changed the US growth factor market significantly. However, that may be because it is the only biosimilar in the market, thus there is not much competition.

One biosimilar for trastuzumab has already been FDA approved. That was done in December 2017, when I was in the middle of writing the paper for APB 980. MYL-1401O was approved by the FDA but is not out on the market yet. Typically, any drug that is approved by the FDA takes a few months to get out to the market. With biosimilars, it might be even a longer process. I am not sure when these drugs are going to be available to give to these patients. I understand that a biosimilar for bevacizumab (Avastin) was approved several months before MYL-1401O, and it is not out on the market yet. There are several legal issues that I am not familiar with.

In our article, we focused on all the biosimilars to trastuzumab with ABP 980. This is a medication developed with Allergen and Amgen. The LILAC trial compared ABP 980 with trastuzumab, and that was a phase III trial showing that ABP 980 had similar efficacy to trastuzumab. LILAC randomized patients to neoadjuvant ABP 980 with paclitaxel versus trastuzumab and paclitaxel. It is in good standing to possibly be approved in the future by the FDA and Europe, as well. In this area, Europe seems to be a little ahead. Many European countries are invested into lowering healthcare costs. We are trying to limit healthcare costs, and I believe having biosimilars will help limit healthcare costs.

Can you expand on the concept of global access as it relates to biosimilars?

It is understandable why some people are cautious, but then as we get more familiar and use the medications, people might be more comfortable using a biosimilar rather than the more expensive parent drug.Trastuzumab has been shown to improve survival—so we consider it a life-saving medication—but some patients might not be able to afford copays, have insurance, or access to healthcare. Healthcare is very expensive, especially in the United States. For example, 1 year of trastuzumab costs about $50,000 for a patient to be treated. If you use it in combination with pertuzumab (Perjeta), it is more than $100,000 per year. That is a big burden for healthcare costs. In lower-income countries, some patients might not have access to these drugs because of the price.

Finding alternatives that are similar in efficacy but cost 20% to 30% less can improve access to these medications for patients who cannot otherwise afford it. Globally, it could provide developing countries access to these medications, allowing a woman to be treated who would have never been able to get this medication.

What looming questions remain with biosimilars in the United States?

On the other hand, the economy of a big country will benefit by reducing healthcare costs. Will we see a reduction in insurance premiums? I don't know. However, we will definitely save money overall, which is good for public health and the economy.We don't really have any real-life experience with using anticancer biosimilars. There are many questions. For example, what will the cost reduction be? Also, how will you choose between using trastuzumab or a biosimilar? Potentially, we may have multiple biosimilars for the same reference products in the next few years, as well as the reference product. If so, will that drop prices even more? Will the physician be making the choice to use a biosimilar, or will it be the insurance companies? Institutions might even have a preference.

In the end, it may depend on whether a physician is comfortable in using the biosimilar. This is something that will take time, and maybe [lead to] a change in culture. It is not going to change overnight. Oncologists may be more comfortable using a biosimilar in patients who are receiving palliative chemotherapy for stage IV cancer. A patient may ask why they are getting a biosimilar rather than trastuzumab, so that is a discussion that might have to happen with patients before the start of therapy. The oncologist will have to be prepared to have this discussion, show the data, and talk about the options.

These drugs are approved when they have shown to have the same efficacy, so you will not be sacrificing efficacy when using them.

von Minckwitz G, Ponomarova O, Morales S, et al. Efficacy and safety of biosimilar ABP 980 compared with trastuzumab in HER2-positive early breast cancer. In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract 151PD.