Sunil Verma, MD, shares his insight on the approval of MYL-1401O, as well as his excitement for the future development of biosimilars across oncology.
Sunil Verma, MD
ABP-215 (bevacizumab-awwb; Mvasi), a biosimilar for bevacizumab (Avastin), was approved by the FDA In September 2017 for the treatment of adult patients with colorectal, lung, brain, kidney, and cervical cancers. This was the first approval of a biosimilar in the United States for the treatment of patients with cancer.
ABP-215 was followed by the approval of MYL-1401O (Ogivri; trastuzumab-dkst), a biosimilar for trastuzumab (Herceptin), in December 2017.
MYL-1401O is approved for the treatment of HER2-positive patients with breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma. It is currently approved for the same indications as trastuzumab; however, Genentech, the manufacturer of trastuzumab, holds an exclusive license for the metastatic gastric cancer indication. Therefore, the companies cannot market MYL-1401O for that purpose until the exclusive license expires.
In September 2017, the FDA accepted a biologics license application for the rituximab biosimilar Rixathon (GP2013), which is manufactured by Sandoz (Novartis). If approved, this biosimilar would be indicated for follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia.
Although biosimilars are just emerging in the United States, the European Medicines Agency (EMA) has been recommending and approving biosimilars for more than a decade. Biosimilars for rituximab, trastuzumab, and bevacizumab are currently approved for use in the European Union.
In an interview with OncLive, Sunil Verma, MD, professor and head of the Department of Oncology at the University of Calgary, medical director of the Tom Baker Cancer Centre, shared his insight on the approval of MYL-1401O, as well as his excitement for the future development of biosimilars across oncology.Verma: We are in a very interesting framework in breast cancer and in oncology at large. We must ensure that we are able to provide effective therapies, but the costs associated with these treatments are substantial. In order for us to incorporate innovation and new therapies, we need to make sure that we also transition some of our old biologics and incorporate biosimilars.
The European bodies have done this tremendously well since 2006 through the EMA’s recommendations and European Union approvals for biosimilars. In many ways, the FDA and Health Canada are now looking at this through the same lens, just at a later date. We need biosimilars to drive down the cost of biologics, and in breast cancer, trastuzumab is one of our key costs associated with treatment for breast cancer. Hence, there is a reason to look at biosimilars for trastuzumab.
It is very important to acknowledge that biosimilars are not generics. These are biological entities that require a very complex mechanism of manufacturing, and a very complex framework for us to assess whether they truly are "biosimilar" or similar in biological principles. Our healthcare regulatory bodies have a different assessment looking at different quality attributes, in order to assess whether there is biosimilarity from a manufacturing or product perspective.
From a clinical and research perspective, the endpoints when we evaluate biosimilars are different than when we evaluate novel agents. When evaluating biosimilars, there is an interest to look at different endpoints, such as response rate in the metastatic setting and pathologic complete response (pCR) in the neoadjuvant setting.
There are at least 7 new biosimilars that are currently being investigated. In Europe, there was a recent approval of a biosimilar from Samsung Bioepis based on a neoadjuvant study. The FDA recently approved a biosimilar from Mylan based on the HERiTAge study that was presented by Hope S. Rugo, MD, of the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, a few years ago. I was the discussant for that trial.
Biosimilars are approved based on the indication of the originator drug. The approval of the trastuzumab biosimilar was based on data for early-stage breast cancer, but was also extrapolated to the gastric cancer setting, as well. Clinicians need to understand the implications of the biosimilar framework for regulatory agencies, and also understand how to incorporate them into practice. There are issues such as interchangeability, automatic substitution, and extrapolation that we need to familiarize ourselves with when we incorporate these therapies in routine clinical practice.In discussions with clinicians about the use of biosimilars, the question that arises is, “How much of this decision is driven by regulatory agencies or insurance providers, as opposed to the clinician?” While the studies have been done and the regulatory decisions have been handed down, there are certain nuances that will be challenging.
For example, let’s look at a combination strategy such as trastuzumab and pertuzumab (Perjeta); could we use a biosimilar there? We don't know. In most of the trials that have been done, the interim endpoints have been pCR, response rate, or progression-free survival, so we do not have long-term data.
It is critical to have strong pharmacovigilance programs and strong-naming programs so that if there are toxicities, in lieu of not having long-term data, we can measure that prospectively in routine and clinical practice. These are conundrums that we need to be prepared for as we incorporate biosimilars into clinical practice.Trastuzumab has been the mainstay and will remain the mainstay for HER2-positive patients. Clearly, as we look at combination strategies and dual-targeted approaches, trastuzumab is the foundation that we build on. Should we incorporate biosimilars into those dual-targeted strategies instead of replacing trastuzumab? That is a challenge we face. While it is unlikely that we are going to have large randomized trials, we need data such as pharmacokinetic data with these biosimilars to justify using them partnered with the dual-targeted approach. Those data are not available yet.Yes. In oncology, there is an approved biosimilar for bevacizumab and trastuzumab, and then we are looking at a rituximab biosimilar. There are also biosimilars for checkpoint inhibitors being evaluated. Therefore, in the future there will be an opportunity to combine biosimilars with biosimilars, which will be very interesting. That is where our partnerships with regulatory agencies will be important, because we as physicians will be able to provide a clinical voice in interpreting the results and even designing some of these trials. Although the manufacturing and quality attributes are assessed by regulatory agencies, there should be a clinical perspective on the evaluation of these therapies. The key ones in breast cancer is definitely filgrastim and G-CSF products that we have, as well as trastuzumab, and the countries in which bevacizumab is approved. Bevacizumab [biosimilars] are also being investigated.Biologics are complex drugs to develop, and there is now a regulatory pathway for agencies to evaluate them. I would encourage clinicians to review their regulatory framework that exist for approving this, and to understand that it is not the same clinical assessment framework that we use when we assess innovative products. This framework is driven more by the regulatory agencies identifying the manufacturing and clinical quality attribute assessment. Clinical trial information is not the key driver like it is for the originator agent.