An Evolving Market: A Look at Biosimilars

Published on 06 March 2017

Brand-name biologics have been extensively used for the past decade without competition. Biologic medications have opened the door to new possibilities for personalized, targeted medicine, but as patents end and biosimilars begin to enter the market, new therapeutic possibilities are emerging.

Projected to save billions of dollars in U.S. health care costs, biosimilars are a highly anticipated alternative to some of the most expensive medications on the market. However, from ongoing patent litigation and legislation to complex development processes, pharmacists and the U.S. prescription drug industry are left to hang on the cusp of a revolution. The destination may not be clear, but a look at the development, recent legislation, and anticipated effects of biosimilars on the market and the profession is enough to make one fasten their seatbelt.

Produced by living organisms, biologics have a more complex structure than standard, chemically based medications composed of small molecules. The active components in biosimilars are large, complex protein and polypeptide macromolecules. Leah Christl, Ph.D., associate director for therapeutic biologics at the U.S. Food and Drug Administration (FDA), elaborated in the April 2016 issue of the FDA Consumer Health Information publication.

“Biologics are different from conventional medications,” Christl said. “Conventional medications are generally made from chemicals, or chemically synthesized, and therefore their structure can be relatively easily defined. Because biologics come from living organisms that are variable in nature, they are generally more complex and not as easy to define and characterize.”

Terry Seaton, Pharm.D., FCCP, BCPS, professor of pharmacy practice at St. Louis College of Pharmacy, explains that with biologics, it is not only the end product that is complicated, it is the creation process as well. Medications produced by living organisms are not revolutionary, but in the case of biologics, the organism’s genetic information is altered to stimulate production of the medication.

“With many small-molecule medications, like aspirin, the manufacturing process is relatively simple and not proprietary,” Seaton explained. “But with biologics, the process of making them is extremely complex, and it is also proprietary. Manufacturers start with a line of cells and insert new genetic information into their DNA. Then, they culture those cells and grow them, and those cells secrete the medication. The process is time consuming and very controlled, and no one but the company really knows the exact details.”

While many European countries have already reaped the benefits of a strong biosimilar market, the first FDA-approved biosimilar did not hit the U.S. market until the 2015 introduction of Zarxio, a product of Sandoz Inc., the generics arm of Novartis AG. Unlike generics, biosimilars are not copies of a brand-name medication. They are “highly similar” to a reference product (the original, brand-name medication) and produce the same biological effects as the reference product.

As is often the case with advances in drug development, the advent of biosimilars came with some initial hesitation. Differences in the immunogenicity of reference products and biosimilars created some concerns that patients successfully receiving biologic treatments may experience adverse immune responses to biosimilar substitutes. Concerns also have been raised about discrepancies between the pharmacokinetic and pharmacodynamic profiles of innovator reference products and biosimilars, which could translate to differences in efficacy and side effects.

While, in theory, these questions may have merit, the review and approval process for biosimilars has alleviated most concerns. Before a biosimilar is approved, FDA experts verify that the biosimilar functions the same way as the reference product and is of the same strength and dosage form.

“Patients can rest assured that they’ll be able to rely upon the safety and effectiveness of an FDA-approved biosimilar, just as they can rely on the reference product that the biosimilar was compared to,” Christl said.

Seaton added, “I’m confident that the U.S. regulation of biosimilars is good. It’s solid. Biosimilars didn’t catch them [the FDA] off guard. They learned from the European experience. They have patients’ best interests in mind, and they are smart people. They are not going to approve products that are not good for patients.”

Fostering Innovation With Legislation

Even though many drug companies began developing biosimilars in tandem with their reference product, only three biosimilars have been approved by the FDA — Zarxio (a biosimilar version of filgrastim), Inflectra (a biosimilar version of infliximab), and Erelzi (a biosimilar version of etanercept). Despite the low number of biosimilars on the market, key legislation has already been passed in anticipation of market growth. To introduce more price competition and encourage innovation in the biologics market, President Barack Obama signed the Patient Protection and Affordable Care Act (PPAC Act) into law on March 23, 2010. This law provides an abbreviated approval pathway for biosimilars.

Similarly, in June 2016, Missouri Governor Jay Nixon signed legislation critical for the substitution of interchangeable biologic medicines. Jim Greenwood, Biotechnology Innovation Organization (BIO) president and chief executive officer, commented in a BIO press release published in June 2016.

“By signing Senate Bill 875 into law, Governor Nixon has added Missouri to the list of states that allow retail pharmacies to substitute interchangeable biologic medicines.”

Missouri is one of 20 states with laws allowing pharmacists to substitute an interchangeable biosimilar without a prescribing physician intervening. There are varying opinions about substituting biosimilars for reference products, which in most cases requires a new prescription. For some, this requirement presents an obstacle.

“The challenge, in many cases, is that biosimilars may not be automatically substitutable,” explained Adam Kautzner ’01, Pharm.D., vice president of formulary and drug trend solutions at Express Scripts Inc. “You’ll have to get a new prescription for the biosimilar product.”

For others, the substitution of a biosimilar warrants the involvement of the prescribing physician.

“The prescriber should know when medications are being substituted,” Seaton said. “With biologics and biosimilars, the effect that people get can be more variable, and the diseases that are being treated are more serious. Both the physician and pharmacist need to know what is happening with the patient.”

The Cost of Competition

The high cost of biologic medications is a major issue for many patients. With the introduction of biosimilars into the market, patients are afforded treatment options at a lower cost.

“Inflammatory conditions like rheumatoid arthritis, psoriasis, and Chron’s disease cost more than any other disease state,” said Kautzner. “From an overall payer perspective, more competition in the market will cause the cost to come down, especially if there is a directly competing biosimilar.”

The added bonus of a rise in biosimilars is the innovation that accompanies competition. Encouraging manufacturers to innovate not only increases physician and patient treatment options, but it also increases patient access to these new innovations. More cost-effective biosimilars create a financial opportunity to invest in new treatment options.

Impact on the Profession

In the next few years, biosimilars have the opportunity to create significant health care savings. For the biosimilars market to grow and remain stable, policy makers, manufacturers, physicians, pharmacists, patients and payers will have to work together. Strong competition in the market begins with cooperative legislation both at the national and state levels. Legislation encouraging physicians to prescribe biosimilars, comparable to laws that promote generic prescribing, is a likely approach. Policymakers are also focusing on the pharmacist’s role in substitution, as demonstrated by the Missouri Senate Bill 875.

The components that make for a sustainable biosimilar market are just as complex as the molecular structure of the medications, and pharmacists are sure to play an integral role. The exclusivity of the current biosimilar market has affected pharmacists working in hospital settings the most. Community pharmacists will play a different, but equally important role.

As legislation continues to be passed regarding the interchangeability of biosimilars, community pharmacists will be working with physicians and payers to make decisions regarding what biosimilars should be prescribed. Pharmacists are already the liaison between patients and payers. With the advent of biologics and biosimilars, interactions between pharmacists and payers will become more frequent and complex.

Teaching for the Future

Community pharmacists will also play a critical role in patient education. Despite most biologic medications being administered in a hospital or clinic, community pharmacists are often the most accessible source of health care information. Pharmacists will be required to provide information and education to patients receiving biologic treatments, even though they may not be providing the medication.

“When you become a pharmacist, your learning never ends,” Seaton explained. “Biologics and biosimilars are great examples of how pharmacists have to keep up with drug development. These medications are new, so we have to learn about them to properly educate our patients. The patient may be receiving their biosimilar from a specialty pharmacy, but they are filling the rest of their medications in their regular pharmacy. That pharmacist has to be a resource for the patient.”

The changing landscape of biologics and biosimilars will also inform the way institutions like St. Louis College of Pharmacy educate the next generation of pharmacists.

“We are obligated to teach students for the future,” Seaton said. “The work we do in the classroom may not always seem practical, but we are aiming at a target that is not today. We have to equip students with practical knowledge as well as a framework of understanding that allows them to learn and remain at the forefront of the profession.”

The development, legislative intricacies and implications for the future of biosimilars and pharmacy is a collection of intertwined issues. Pharmacists will continue to be a critical link, ensuring patients receive optimal benefit from these therapies.

This story was first published in the fall 2016 issue of Script. Visit stlcop.edu/script to read more and access previous issues.

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