Biosimilar: Coming to a pharmacy near you

After brisk sales through specialty pharmacy, biosimilars are moving toward community pharmacy. Basaglar (insulin glargine injection; Lilly, Boehringer Ingelheim), the first FDA-approved follow-on recombinant insulin, could hit pharmacy shelves in December.

Manufacturers have been prepping for years. About half of the states have enacted statutory or regulatory frameworks for biosimilar substitution. Nearly all were written and sponsored by industry, with little or no input from pharmacy.

Pharmacy benefit managers and payers have been positioning biologics, such as Lantus (insulin glargine injection, Sanofi-Aventis), Neupogen (filgrastim, Amgen), and Remicade (infliximab, Johnson & Johnson), to take advantage of biosimilar competition from Basaglar, Zarxio (filgrastim-sndz, Novartis), and Inflectra (infliximab-dyyb, Celltrion). Industry observers count another 50-plus biosimilars in the FDA approval process.

“Biosimilars are the future of pharmacy,” said Jillanne Schulte, director of federal regulatory affairs for the American Society of Health-System Pharmacists. “We are seeing the forefront of the coming wave of innovation in health care. When biosimilars hit community pharmacy, issues like interchangeability that have been important in specialty settings are going to explode. Biosimilars are the frontier of medicine.”

Biosimilar, not generic

Biosimilars have been a staple in European healthcare for a decade. The European Medicines Agency (EMA) created its biosimilars pathway in 2005 and has approved at least 19 biosimilars in six product categories: epoetins, filgrastims, follitropins, growth hormones, insulins, and monoclonal antibodies.

EMA-approved biosimilars are priced about 30% below the reference product, according to Express Scripts. The PBM projects US savings of nearly $22.7 billion by 2024 from the approval of Zarxio and Inflectra and $250 billion from a basket of 11 biosimilars currently awaiting FDA approval.

The actual savings from biosimilars is anybody’s guess. Zarxio, the first and so far only biosimilar to reach market, is priced about 15% below its reference product Neupogen.

Inflectra has been approved, but marketing has been delayed by legal challenges. A settlement reached earlier this year allows Basaglar to enter the market after December 15, 2016.

Congress gave the FDA the authority to create biosimilar approval pathways in 2010 under the Biologics Price Competition and Innovation Act (BPCIA). BPCIA was rolled into the Affordable Care Act and created two product categories, biosimilars and interchangeables.

Biosimilars are not generic versions of reference biologic products. Generics are chemically identical to the reference brand name drug.

The “FDA Overview of Biosimilar Products” describes biosimilars as highly similar to the reference product and having no clinically meaningful differences in safety and efficacy.

An interchangeable product is a biosimilar that can be expected to produce the same clinical result as the reference biologic in any given patient.

What “interchangeable” means in practice is not clear. Sponsors may have a greater burden of evidence to achieve the interchangeable label, but the FDA has not yet defined interchangeable or a pathway that leads to interchangeability.

“There is still a lack of definitions regarding biosimilars,” said Carmen Catizone, MS, RPh, DPh, National Association of Boards of Pharmacy executive director. “Boards of pharmacy are still waiting for clarification from the FDA and are acting based on what information they have.”

Orange Book to Purple Book

The BPCIA states that an interchangeable biologic may be substituted for the reference product by a pharmacist without the intervention of the prescriber. But substitution and other dispensing practices are governed by the states.

States are enacting industry-crafted legislation that reminds some pharmacists of early generic substitution rules that required two-line signatures or check-off boxes (see Sidebar). None of the state laws passed to date references the Purple Book, the FDA’s new biosimilar compendium.

The Purple Book is intended to do for biosimilars what the Orange Book does for generics, create a comprehensive resource of approved products, their reference products, and interchangeability status.

The Purple Book lists all biologics licensed by the FDA under the Public Health Service Act (PHSA), the pathway by which most biologics have been marketed. But a few protein products, including insulin glargine, have been approved under Section 505 of the Federal Food, Drug, and Cosmetic Act (FFDCA).

Products licensed under the FFDCA are not technically biologics or biosimilars because they were not licensed under biologic or biosimilar pathways.

FDCA 505 protein products, including Lantus and Basaglar, are listed in the Orange Book. That will change on March 23, 2020, when the BPCIA allows the FDA to deem products licensed under FFDCA section 505 as having been licensed under the PHSA. Once those products are deemed to be biologics-licensed, they presumably will move to the Purple Book.

Pharmacy and biosimilars

“We are seeing a huge impact from biosimilars, and it is only going to grow,” said Ali McBride, PharmD, MS, BCPS, BCOP, clinical coordinator of Hematology/Oncology at the University of Arizona Cancer Center. “Pharmacists have a huge role to play regardless of their site of practice.”

Clinical pharmacists who deal with biologics are acutely attuned to the challenge of biosimilars. Payers are pushing biosimilar substitution for Neupogen and talking about future switches as other biosimilars come to market. Community pharmacy can expect a similar push when Basaglar arrives.

“Express Scripts made Lantus our preferred insulin product for all new therapy starts,” said company spokesman David Whitrap. “This positions our clients to maximize potential cost savings due to the forthcoming head-to-head price competition. Basaglar and Lantus are much more similar to each other than any other two insulins on the market. We expect that many payers, physicians, and patients will be willing to switch if one of the products offers a significant price discount to the other.”          

A high stakes game

Pharmacists are in the middle of biosimilars. Just as many prescribers and patients were unclear on the concept of generic substitution and resisted change, many will resist biosimilar substitution. Payers will push just as hard to switch at every opportunity.

“Generics were wild and wooly, and the stakes are even higher with biosimilars,” said Salvatore J. Giorgianni, Jr., PharmD, BSc, CMHE, president and consulting pharmacist, Griffon Consulting Group. “You have to learn the science in a hurry. Managed care is going to mandate interchangeability to save money. If you aren’t knowedgeable about biosimilars, you’re out of luck.”