The first biosimilar product in the United States has been approved, and the time is now for specialty pharmacists to become familiar with the use and regulation of these drugs.


On March 6, 2015, after much anticipation, the FDA approved Zarxio (filgrastim-sndz), the first biosimilar product to get the green light in the United States. Zarxio is not an interchangeable product, however. A biological product approved as interchangeable may be substituted for the reference product without health care provider intervention.

According to the FDA, “A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action, route(s) of administration, dosage form(s) and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the innovator product.”

A layman might consider Zarxio as a “generic” to Neupogen (filgrastim). Biopharmaceuticals (or biotech products), however, are large, protein-based molecules. These “bio-manufactured” products are often made from bacteria and other living cell organisms. As one can imagine, separating the necessary material from the balance of the living organism requires great expertise. With any living material, there may be great variability. That variability makes the process of creating biopharmaceuticals different from the small-molecule process, which is pretty much basic chemistry. To be clear, Zarxio is not a “generic” version of Neupogen and, as such, is not a chemically identical (ie, bioequivalent) copy.

Since Zarxio is not considered by the FDA to be interchangeable with Neupogen, pharmacies cannot, as a matter of practice, substitute Zarxio for Neupogen without receiving approval from the prescribing physician or operating under a collaborative practice agreement or treatment protocol providing such authority to make the change.

PURPLE: THE NEW GOLD STANDARD
The FDA first published Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations, known as the “Purple Book,” on September 9, 2014. It lists “biological products, including any biosimilar and interchangeable biological products licensed by the FDA under the Public Health Service Act (PHS Act).” The book includes the date a biological product was licensed under 351(a) of the PHS Act, whether the FDA evaluated the biological product for reference product exclusivity under section 351(k)(7), and whether the FDA has determined a product to be biosimilar or interchangeable with an already licensed FDA-referenced biological product. The biosimilar and interchangeable products are listed under their reference product. This resource will be the “gold” standard for how biosimilars may be substituted.

WHY THE PUSH FOR BIOSIMILARS?
With the impending patent expiration of a number of biotech products, the global markets have been looking forward to biosimilars. The goal of these “like” products is to provide a lower cost alternative to the brand-name drugs, as generics do, while providing the same safety and efficacy of the innovator. As we know, specialty products can cost $1000-plus per dose. The sales innovator specialty products are in the billions of dollars and, thus, efforts to obtain approvals on lower-cost alternatives are very important. Yet, as stated, biosimilars are expensive to make and ultimately cannot be freely substituted, so they will likely never show up on the $4-per-30-day-supply list.

In the retail setting, the numbers for generic drug dispensing are astounding: according to the FDA, about 85% of all retail prescriptions are currently filled for generic drugs. There are few therapeutic classes of long-term-use products for which a generic is not available. Generic drug use has changed the market dynamics of our industry. Pharmacy regulations and statutes have been very pro-generic and, in many states, a pharmacist is required to provide the patient with the lower-cost alternative. Payer agreements with pharmacies will, in most cases, only pay for the price of a generic when available at a maximum allowable ingredient cost.

I believe that after 3 decades, the typical patient and his or her physician are over the equivalency hump. It is the individual state boards of pharmacy, however, that govern the substitution laws in the United States. As a result of pending approvals in the biosimilar space, many states have begun to address and amend their regulations to make them applicable to biologics.

In the last couple of years, more than 20 states have reviewed their laws and regulations regarding substitution with a biosimilar. According to the National Conference of State Legislatures, commonly seen provisions require that:
  • A biological product being considered for substitution must first be approved as interchangeable by the FDA
  • The prescriber can prevent substitution by specifying “dispense as written” or “brand medically necessary”
  • The physician is informed of any substitution made at the pharmacy
  • The patient is informed that the original prescription was changed and a biosimilar was dispensed
  • The patient consents to the substitution
  • The pharmacist and physician retain records of any biological medication substitution.
SPECIALTY PHARMACY: THE TAILOR-MADE SOLUTION
Specialty pharmacy has been at the forefront in tailoring therapies for patients, working closely with all stakeholders while focusing on improving outcomes. Specialty pharmacy continues to provide holistic patient care with an emphasis on services that include:
  • Integrated health care provider services
  • Coordination of benefits across multiple tiers
  • Expanded drug therapy management counseling and patient education
  • In-depth patient education about adverse reactions
  • Clinical monitoring and dosage adjustments
  • Patient adherence and persistency programs
Formulary management has long been a process where decisions made at a payer or pharmacy benefit manager (PBM) level are enforced at the pharmacy. Today, more than 50% of specialty products are filled by payer-owned specialty pharmacies, such as Accredo, CVS/caremark, Optum, Catamaran, Prime Therapeutics, and others. In these specialty pharmacies, the payer’s drug benefit policy is fully enforced and can be a great catalyst in driving dispensing toward biosimilars.

My crystal ball tells me that payers will have significant influence on which biosimilar manufacturers will ultimately be used and for which branded biotech branded products, regardless of the degree of savings. In the world of hepatitis C, we have already seen that PBMs can be very successful in determining which brands are used and in securing lower prices. We should anticipate that we’ll see the same trends in biosimilars.

Prescribers will be encouraged and likely incentivized (directly or via lower co-pays) to prescribe biosimilars, depending on state pharmacy laws that allow pharmacists to substitute for the brand name drug or instead of competing preferred biosimilar manufacturers. With e-prescribing, this process can even occur at the point of prescribing so that a “clean” script lands at the specialty pharmacy.

CLOSE IS GOOD ENOUGH
Let’s look at Zarxio as the test case for biosimilars in the United States. In the controlled and closed ecosystem of specialty pharmacy and with the significant price points of biotech products, the future is bright for these new products. In our free market system, competition will drive utilization if all else is equal. In this case, close is good enough. SPT

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About the Author
Dan Steiber, RPh, is a principal of D2 Pharma Consulting LLC (d2rx.com) and is responsible for commercial operations, trade-supply chain strategy development including 3PL selection, regulatory oversight, and “operationalizing” organizations. He has served in several senior positions in pharmacy, distribution, and industry over the course of his 40-year career. Mr Steiber is a licensed pharmacist in Texas, Washington, California, and Pennsylvania. He is affiliated with several professional associations and publications and is a frequent speaker on behalf of many professional organizations. He graduated from Washington State University College of Pharmacy and has participated in a variety of postgraduate programs in law and business development/marketing at Harvard University and Northwestern University. Dan currently resides in Highland Village, Texas.