To integrate biosimilars into clinical practice, physicians must understand variation in reference products, data, naming, labeling, interchangeability, substitution and overall drug safety.
In the last 20 years, large-molecule biological medicines, such as Enbrel and Humira, changed the way doctors treat inflammatory diseases, such as rheumatoid arthritis, psoriasis and Crohn’s disease.
These medications are complex isoforms made from living organisms and developed to target certain cells and systems in the body. Unlike a standard chemically derived drug, biologics are created using recumbent DNA technology, advanced bimolecular know-how, and rigorous safety protocols.
But now, as the patent time runs out on biologics, regulatory agencies are buzzing about the use of biosimilars. The medicines, which are biologically and molecularly similar to the original biological reference products, are starting to be approved for use in rheumatology patients, and pharmaceutical insiders predict these drugs will be a game changer when they hit clinics in the coming years.
“Americans should see biosimilars in clinic in the next year or two,” said Stephen Feldman, MD. Feldman, a dermatologist at Wake Forest University in North Carolina, uses biological medicine to treat psoriasis. He says biologics are useful in any disease where an over-active inflammatory response fuels symptoms.
To date, the European Medicines Agency (EMA) has approved 19 biosimilars for use in European markets, and the FDA has approved one, Zarxio, in March. Zarxio will primarily used in cancer treatment.
In June, Feldman published a paper in Seminars in Arthritis and Rheumatism that addressed issues of selection, prescribing and monitoring of biosimilars. “To successfully and confidently integrate biosimilars into clinical practice, physicians must understand factors such as variation in innovator/reference products, extrapolation of data, naming and labeling, interchangeability and automatic substitution and pharmacovigilance,” he wrote.
Writing in the Sept. 16 issue of RMD OPEN, Diana Skingle, on behalf of the EULAR Standing Committee of People with Arthritis/Rheumatism in Europe (SCPARE), said that as is “common with the introduction of all new medicines, biosimilars have raised a number of questions and concerns in the minds of patients, ranging from the approval process to safety and risk.” Patients with rheumatic and musculoskeletal diseases must understand the complexities associated with any new medication they take, she wrote. But, “urgently needed are clear codes of practice, written in lay language and drawn up with the involvement of patients,” Skingle wrote.
Both papers say that physicians must be well-versed in the differences between biologics and biosimilars as they help their patients navigate the use of these medicines.
Biosimilars not so novel
While biosimilars are described as the second generation of biologics, Feldman said that’s an inaccurate depiction of the medicines. In fact, people have been taking biosimilars for years.
“People have been using biosimilars for the last 10 years but didn't know it. Biologicals are so complicated they cannot be duplicated, so the branded drug is not the same today as it was even a year ago,” Feldman said.
Cost and safety of biosimilars
If cost savings is your goal, Feldman says a switch to biosimilars could take off 20 percent of your monthly prescription. That may not be enough when some biological medicines can cost upwards of $20,000.00 per year.
“The price will come down because of competition when biosimilars are introduced, but it may not be enough to dramatically improve access to the drugs,” Feldman said.
In Europe, where biosimilars are already being used regularly, some patients and prescribers have seen as much as a 30 percent reduction of cost. Because of this cost reduction, EULAR states that many patients fear their doctors will switch their biologics for a cheaper biosimilar. There are no current guidelines for switching a biologic for a biosimilar, so EULAR stresses that each patient be aware of what’s being prescribed.
As for safety, Feldman said he considered biosimilars to be as safe as their reference products.
“Most people have very few side effects,” said Feldman. “There will continue to be a Black Box warning on the medicines because they can reactivate Tuberculosis if you have it in your system, but we can easily test for TB before initiating treatment.”
Safety and labeling
While assumed to be safe, patient and consumer safety groups, like the Patients for Biologics Safety and Access (PBSA), warn that the use of biosimilars should prompt extensive safety surveillance and vigilance among providers.
In a recent letter sent the Senate Committee on Health, Education, Labor and Pensions (HELP) wrote that “…biosimilars are not generic copies of biologic medicines.”
Larry LaMotte, vice president of Immune Deficiency Foundation (IDF) and co-author of the letter said biosimilars, “… (have the) potential for huge impact. People need to recognize that there are no generic biologics, these medicines are not identical copies.”
While LaMotte said he would like to see biosimilars in clinical practice, he wants to make sure the FDA considers safety and a patient’s perspective.
In late August, the FDA released a draft guidance outlining the FDA’s proposed guidelines for naming biologics and biosimilars. A distinctive naming convention was needed to clearly identify biological products to improve drug safety and clearly differentiate biological products that are not interchangeable. (The FDA is expected to rule on the draft guidance by Nov. 11.)
The guidance suggests that reference products and biosimilars adopt an FDA-designated suffix unique to each product. For example, the FDA nonproprietary name of a reference product could be “replicamab-cznm,” and a biosimilar to that product could be “replicamab-hixf.”
But for interchangeable biological products that are switched between the reference product and biosimilar, the FDA will decide whether the nonproprietary name for such a product should include a distinct suffix, or whether it should share the same suffix as its reference product (e.g., the nonproprietary name of both the reference product and the interchangeable product could be replicamab-cznm).
Steven R. Feldman. Inflammatory diseases: Integrating biosimilars into clinical practice.Seminars in Arthritis and Rheumatism. 2015 Jun;44(6 Suppl):S16-21. doi: 10.1016/j.semarthrit.2015.04.003. Epub 2015 Apr 9.
Diane Skingle. Biosimilars: what do patients need to consider?RMD Open 2015. September 2015. doi:10.1136/rmdopen-2015- 000141