What You Should Know About Biosimilars
Less-expensive versions of biologic drugs have hit the U.S. market.
A new generation of arthritis drugs is arriving in the United States, and they could make expensive biologic drugs accessible to more people. Beginning in 2016, the U.S. Food and Drug Administration (FDA) began approving biosimilars – copycat versions of familiar biologic medications – to treat autoimmune forms of arthritis, including as rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis and juvenile arthritis.
Approved medications are:
- Inflectra (infliximab-dyyb), a biosimilar of Remicade (infliximab)
- Erelzi (etanercept-szzs), a biosimilar of Enbrel (etanercept)
- Amjevita (adalimumab-atto), a biosimilar of Humira (adalimumab)
- Renflexis (infliximab-abda), a biosimilar of Remicade (infliximab)
- Cyltezo (adalimumab-adbm), a biosimilar of Humira (adalimumab)
So what exactly are biosimilars? How do they work? And what’s with those crazy names? Here’s what you need to know:
“Biosimilar” is not the same as “generic.”
Generics are exact copies of chemically synthesized medicines. Biosimilars are not-quite-exact copies of biologics – drugs that are impossible to replicate perfectly because they are very large and complex molecules derived from living substances, such as human and animal cells, yeast and bacteria.
Partly because of this, the U.S. Food and Drug Administration (FDA) has a different process for approving biosimilars than for other drugs. When seeking FDA approval, a manufacturer has to show that its biosimilar drug is, among other things, as safe and effective as the original biologic – called the “reference product” – and works in the same way.
“Biosimilars have the same amino acid sequence as biologics, [the same] potency, dosing, route of administration and clinical effects. The ways in which they differ aren’t significant,” explains Jonathan Kay, MD, director of clinical research in rheumatology at University of Massachusetts Memorial Medical Center in Worcester.
Additionally, once a drug has been shown to be biosimilar to a reference product, it can be approved for all the same conditions (or “indications”) as that reference product even if it hasn’t been specifically tested for each and every condition, thanks to a concept called “extrapolation.”
Biosimilars might cost less.
Biologics are expensive. They can cost a patient several thousands of dollars out of pocket each month, depending on the patient’s insurance plan. Biosimilars are predicted to cost less – although ultimately how much less (and whether consumers will see any savings) is anyone’s guess. Additionally, competition from biosimilars may drive down the price of branded biologics, too, though that’s not a given, according to Eric Matteson, MD, (now retired) rheumatologist and professor of medicine at Mayo Clinic in Minnesota.
What’s in a Name?
Biosimilars still face some outstanding issues, such as what non-proprietary name to give the new drugs. These names (which are separate from a drug’s brand name) need to be unique and distinct from the reference biologic for ordering, prescribing, dispensing and record-keeping purposes.
Currently, those approved are following the FDA’s draft guidelines that state that a biosimilar’s name should comprise the core name of the reference product plus a unique four-letter suffix to differentiate it from the reference drug and from any biosimilar of that very same reference drug that might come along in the future.
The “Interchangeability” Issue
Another area of controversy is the designation of so-called “interchangeable” drugs. According to the FDA, “[a]n interchangeable biological product is biosimilar to an FDA-approved reference product and meets additional standards for interchangeability.”
The concern for many patients and doctors is that “interchangeability” opens the door to the pharmacist to substitute a biosimilar for the branded biologic without consulting the prescribing physician or even making a patient aware of the substitution. Many states have passed or are considering laws governing substitutions, although some doctors, including Dr. Matteson, would prefer to see a more uniform, nationwide approach.
The Arthritis Foundation, which has been instrumental in getting the legislation passed in states, maintains that doctors and patients need to be informed in a timely manner if a substitution occurs, and that doctor should to be able to override a substitution in certain cases.
As of now, there is no pathway for a biosimilar to receive an “interchangeable” designation, because the FDA has not yet defined the standards that would need to be met. None of the biosimilars approved for arthritis is deemed interchangeable with its reference product.
Although biosimilars have been available worldwide – including Japan, Canada, Australia and many countries in Europe – patent disputes have delayed their introduction in the U.S. However, some have managed to reach consumers: Pfizer launched Inflectra in November 2016 and Merck launched Renflexis in July 2017.
How all of these factors will play out is still unclear. Nor is it clear how quickly and whole-heartedly patients and doctors will embrace biosimilars.
“As with any new paradigm, there’s some uncertainty,” notes Dr. Kay. “But once these drugs are introduced into clinical practice and patients and physicians see they are just as effective at a lower cost, they will want to use