Cornelius F. Waller, MD: I feel very comfortable using biosimilars. In Europe, we have more than 10 years of experience using biosimilars. Filgrastim was developed in the early years of the new century and was actually approved in Europe in 2006. In 2007, filgrastim came to the market. I feel comfortable because I know how to develop such a drug. This occurs through a very thorough development plan issued by regulatory agencies, such as the FDA or [the European Medicines Agency, EMA]. Some people might argue that there is little data available in comparison to the reference product. In my opinion, this is not the issue with biosimilars. Due to a very extensive preclinical problem and a phase 1 study, you have a phase 3 study—a sensitive disease model. There is also a clear postmarketing plan for pharmacovigilance. Therefore, I consider this to be a safe group of drugs to use.
In many situations, there is no issue. In patients who have a short period of drug exposure—for example, in the adjuvant setting of HER2/neu-positive breast cancer, where you have a year of adjuvant treatment—one could argue that there’s much more data on the originator product, so far. This could be an argument, but in most of the cases, I don’t see an issue when choosing a biosimilar. In Germany, the decision is not based upon the physician alone. The pharmacists and regulatory agencies, on the state and on the national level, are also a part of this decision process.
Biosimilars, in my opinion, are a major advancement not only in the field of cancer treatment but also in rheumatology and gastroenterology, where we have a couple of antibodies that have been used successfully for quite a while. In highly developed countries, as in the United States or in many European countries, you have access to these drugs through your health care plan or insurance coverage. But there are many countries in the world where this isn’t the case. For example, Herceptin, the originator trastuzumab, was not available due to its high cost. I hope that the development of these biosimilars, through recent technology, will enable us to treat more patients worldwide with these complex, expensive compounds.
Extrapolation of indications means that a biosimilar can be used for all indications that the reference product has been used and approved for. However, for biosimilar development, it is usually enough to have 1 sensitive disease model where you show, in a phase III trial, that it’s similar to the reference product. Regulatory agencies have clear-cut conditions when extrapolation can be done. These differ a bit between the FDA requirements and the EMA. One of the issues, for example, is that it is clear that the mode of action of the biosimilar is the same in the different diseases for which the indication is granted for. Therefore, due to the thorough regulatory process, extrapolation, in my opinion, is something that can be done. I don’t have a problem using filgrastim in breast cancer, where most of the studies were performed and led to an approval of biosimilars, or in other diseases where neutropenia is an issue.
In clinical use, filgrastim has been on the market for more than 10 years in Germany. The market share is approximately 75% to 80% of prescriptions, on average, over the whole country, which shows the acceptance of this drug. And, in addition to that, monoclonal antibodies recently became available as biosimilars. For example, we have replaced part of our rituximab administration to patients with biosimilars without seeing any difference in efficacy or side effects. The same was true with filgrastim.
Hope S. Rugo, MD: I wouldn’t have a lot of compunction for switching a patient from a reference biologic to the proposed biosimilar. For people who are on the drug for a very long time, where there’s a cost issue, we might switch. Or, for example, if the university is saying “This is the agent we’re giving,” we would switch. Otherwise, I think it’ll be more of an issue in people who start new on HER2-targeted therapy. In those situations, I would certainly feel comfortable using a biosimilar. In the United States, we’re often driven by what insurers want and what the pricing structure of the university is.