Similar, Not the Same; The Road Ahead for Biosimilars
History-making approvals of medicines usually introduce brand new treatment pathways or novel therapeutic approaches. That all changed in March of last year, when the U.S. Food and Drug Administration (FDA) marked a new type of regulatory milestone: the approval of the first biosimilar in the United States.
At Genentech, we have long-supported the FDA’s efforts to implement a science-based pathway for the approval of biosimilars. Patients’ interests have always been front-and-center for us, and we believe having more treatment options is a good thing for patients. Still, we must not forget that there are a number of unknowns when it comes to biosimilars and their use in clinical practice. By embracing transparency and a scientific approach to the assessment, approval, and use of biosimilars, we can together forge the path that best supports doctor and patient choice.
"By embracing transparency and a scientific approach to the assessment, approval, and use of biosimilars, we can together forge the path that best supports doctor and patient choice."
To understand some of the unknowns around biosimilars, it’s important to first understand the difference between biologic medicines and small molecule medicines. A biologic medicine is made from living cells and is a complex large molecule like a therapeutic antibody. A small molecule medicine is made by chemical reactions and is a much simpler molecule, like a statin or aspirin.2 These medicines are different from biologics – think of it as the difference in complexity between building a fixed gear bicycle versus a jet.
It’s possible to make near exact copies of small molecule medicines, because they have a defined chemical structure and “recipe.”2 These copies are called generic medicines. However, even with the most advanced technologies, scientists can’t make exact copies of biologics.3 That’s why they’re called biosimilars – they are very similar, but not identical, to the original medicines.
When I joined Roche more than a decade ago, biosimilars were still a relatively new concept. The first biosimilar, Omnitrope, was approved in Europe in 2006. In the United States, however, Congress didn’t pave the way for the FDA to approve them until 2010 as part of the Affordable Care Act.7,10 The complexity of biologics made them much more challenging to copy than medicines in pill form, and they required a different pathway to regulatory approval than generics.
Fast-forward to today, and the landscape has changed significantly. There are two FDA-approved biosimilars in the United States, including a monoclonal antibody—a particularly complex type of medicine based on the biology of our immune system.1 The FDA has also provided initial guidance on how biosimilars should be named and what information should appear in their prescribing information, or “labels.” These are important developments for doctors and patients, but a lot of uncharted territory remains.
BY THE NUMBERS
to date in the United States4
submitted to the FDA to date4
approved in the United States5
biosimilar approved in the United States1
Given that biosimilars follow an abbreviated regulatory pathway in the United States, they usually receive approval based on less comprehensive data sets compared to the original medicines. As a result, it will be important to closely monitor biosimilar experience in clinical practice in the years ahead to ensure optimal patient safety and benefit. There are also a few areas, in particular, that I believe require more clarity.
Different medicines need different names
One of the challenges surrounding biosimilars is the most foundational: how should they be named? Doctors, pharmacists, and insurers rely on names (either brand names or so-called “nonproprietary names”) of medicines to help verify that the correct medicine is being administered and, most importantly, to report unintended effects observed with a given medicine. For the same reasons it is also important for patients to know exactly what medicines they are receiving.
Having distinct names for non-identical medicines, even if they are very similar, is important to help ensure that patients, doctors, and pharmacists can differentiate among medicines. We were pleased the FDA released its draft guidance for industry6 on naming in 2015, which proposed distinct names for biosimilars compared to the original medicines. Distinct names are essential to avoid unintended substitution, and allow for appropriate tracking of adverse events reported with either the biosimilar or the original medicine. This also helps us to monitor and detect unexpected differences in safety or efficacy between them.
High standards should be non-negotiable
Interchangeability is another concept with important implications for patients. For the FDA to approve a biosimilar as “interchangeable” its similarity to the original biologic medicine has to be so close that, for example, a pharmacist could give it to a patient even if the patient’s doctor prescribed the original “branded” medicine. This is called “substitution” and is a widely accepted practice for generic medicines in many states, based on pharmacy state law.8
But biologics and biosimilars are more complex than generics. And because biosimilars are not exact copies of the original medicine, I believe patients and their doctors have a right to know exactly what medicine the patient is receiving. I also believe substitution of a biosimilar in place of an original biologic medicine should only occur if the biosimilar is deemed interchangeable by the FDA. Guidance from the FDA will provide us much needed detail about the clinical standards required for interchangeability, and will hopefully specify how those standards will be reflected in biosimilars’ labels.
"Even with the most advanced technologies, scientists can’t make exact copies of biologics. That’s why they’re called biosimilars."
Similar, but not the same
Due to differences in the biology of various diseases, the same medicine that is effective to treat one disease may not work in another. This means that even if the way the medicine is assumed to work may be the same in both settings, a minor change to the medicine’s structure could either have no impact or could lead to a different outcome for patients. This is why the concept of “extrapolation”—applying data from one group of patients, such as those with colon cancer, to a different group of patients, such as those with lung cancer—has been a topic of significant discussion with respect to biosimilars.
For medicines that have demonstrated biosimilarity through rigorous analytical and clinical testing, extrapolation may be appropriate. However, there may be cases where it is necessary to conduct additional clinical studies to confirm biosimilarity of a medicine in certain diseases or indications. This may be because the medicine acts via a different mechanism in one disease compared with another, or the safety profile of the original medicine may differ from one disease or indication to another.
Transparency is key
One of the ways doctors make treatment decisions is based on a medicine’s label, or “prescribing information,” which contains important information such as the proper dosage, approved uses, and possible side effects of a medicine. Patients also use labels to learn more about the medicines they are prescribed. When you consider that many biologics are used to treat serious or life-threatening diseases, it’s even more important to provide doctors and patients with relevant information on these medicines so they can make informed treatment decisions.
I believe doctors and patients should know which medicine a patient is receiving. Biosimilar labeling should be transparent and clearly state that the medicine is a biosimilar version of an original medicine.
We are encouraged that the FDA took a step toward greater transparency for doctors and patients earlier this year with its draft guidance9 on labeling, and that the guidance states a biosimilar’s label should indicate that it is a biosimilar. In the future, I’d also like to see a biosimilar’s label describe the clinical studies the FDA used to approve the biosimilar, which indications were extrapolated, and whether the FDA has deemed the biosimilar interchangeable with the original medicine.
"When you consider that many biologics are used to treat serious or life-threatening diseases, it’s even more important to provide doctors and patients with relevant information on these medicines so they can make informed treatment decisions."
What lies ahead?
Biosimilars are sure to be an increasing part of the ongoing conversation about how we ensure that everyone with a serious disease can get the treatment they need. We look forward to participating in that discussion. There’s no doubt that having choices is a good thing when it comes to medicines. With transparent, science-based standards in place, we can empower patients and doctors to understand these new options and make truly informed treatment decisions.
1 Pahon, E. (2016). FDA approves Inflectra, a biosimilar to Remicade. U.S. Food & Drug Administration. Washington DC: Office of the Commissioner. Retrieved from http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm494227.htm
2 Dorey, E. (2014). Forces Driving the Evolution of Biologics into Biosimilars and Biobetters. The Pharmaceutical Journal: Clinical Pharmacist, 6(9). Retrieved from http://www.pharmaceutical-journal.com/news-and-analysis/features/forces-driving-the-evolution-of-biologics-into-biosimilars-and-biobetters/20067091.article
3 Office of the Commissioner. (2015). Biosimilars: More Treatment Options Are on the Way. U.S. Food and Drug Administration’s Consumer Updates. Retrieved from http://1.usa.gov/1CNyPIg
4 Biosimilar Applications Submitted to FDA (2016). Retrieved from https://www.pharmamedtechbi.com/Publications/The-Pink-Sheet/78/10/Pending-Biosimilars?elsca1=custom&elsca2=rss&elsca3=%3ftopic%3dPerformanceTracker%26source%3dThe%2520Pink%2520Sheet
5 Walsh, S. (2015). FDA approves first biosimilar product Zarxio. U.S. Food & Drug Administration. Washington DC: Office of the Commissioner. Retrieved from http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm
6 FDA Draft Guidance for Industry (2015). Nonproprietary Naming of Biological Products. Retrieved from: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm459987.pdf
7 Patient Protection and Affordable Care Act, 42 U.S.C. § 18001 et seq. (2010). Sec. 7001-7003: Biologics Price Competition and Innovation Act of 2009. 111th Congress. Public Law No. 111-148. Pages 804-821. Retrieved from http://1.usa.gov/1ilNsO3
8 Cauchi, R. (2015). State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars. National Conference of State Legislatures (NCSL). Retrieved from http://bit.ly/1lvTIQM
9 FDA Draft Guidance for Industry (2016). Labeling for Biosimilars Products. Retrieved from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM493439.pdf
10 The Committee for Medicinal Products for Human Use (CHMP) (2006). Omnitrope Authorisation Details. European Medicines Agency (EMEA). Retrieved from: http://bit.ly/1bxcfhc