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Biosimilars will reshape clinical care and managed care pharmacy but ambiguities in the regulatory landscape and knowledge gaps among clinicians seem likely slow adoption.
Biosimilars are set to reshape specialized managed care pharmacy. But litigation among sponsors of biosimilar and reference biologic products, stakeholders’ pushback against the FDA’s recently-announced biosimilars naming rules, and clinician knowledge gaps and concerns might all slow adoption of biosimilar therapeutics.
That’s according to two analysts at the AMCP Managed Care & Specialty Pharmacy Annual Meeting, in Denver. They spoke at the meeting’s March 30 session, “Keeping Up with Biosimilars: The Latest on Regulation, Utilization, Monitoring, and Pipeline.”
Clinician confidence in biosimilars’ safety “will be crucial” to their acceptance and uptake, noted C. Douglas Monroe, RPh, MS, a drug information consultant based in Mission Viejo, California.
There are “key knowledge gaps” in physicians’ understanding of the regulatory landscape for biosimilars, he cautioned.
Patent disputes and a range of policy issues also need to be resolved, including naming and labeling, interchangeability, and the emergence of state-level biosimilar legislation.
A key court fight between Amgen and Sandoz regarding the biosimilar version of filgrastim is heading to the U.S. Supreme Court, and the ruling “could have huge implications for biosimilars moving forward,” noted Jennifer M. Day, PharmD, pharmacist project manager at Kaiser Permanente’s Drug Information Service in Downey, California.
“So far, it’s keeping a lot of patent attorneys gainfully employed but it is also creating a lot of uncertainty about when these biosimilar products will get to market,” Day said.
The Biologics Price Competition and Innovation Act (BPCIA), signed into law in 2010 as part of the ACA, amended the Public Health Services Act to provide an abbreviated pathway for licensure of biologics proven to be “biosimilar” or “interchangeable” with already FDA-licensed biologics. It states that biosimilar sponsor applicants “shall provide notice” to branded reference biologic product sponsors “not later than 180 days before the date of first commercial marketing” of the biosimilar product.
In Amgen vs. Sandoz, a U.S. District Court ruled in March 2015 that there is no need for biosimilar sponsors to await FDA approval before giving their 180-day notice of commercial marketing, but a federal appeals court reversed that decision, ruling that the sponsor must wait for FDA approval before giving notice. Biosimilar sponsors argue that gives branded biologics’ sponsors an additional half-year patent protection period that was never intended by Congress.
Biosimilarity is defined in the BPCIA as meaning that a product is “highly similar” to its reference product and that “there are no clinically meaningful differences” between the two in terms of safety, purity, or potency. Biosimilars’ regulatory approvals are abbreviated compared to approvals for novel biologics because their biosimilarity is demonstrated for reference products for which efficacy and safety have already been established for the indication in question, Monroe explained.
Pushback against naming guidance
Stakeholders are also already pushing back against the FDA’s January 2017 final guidance for naming biosimilars. The FDA requires that sponsors propose a four distinct and lower-case-letter suffix attached to the product’s generic or “proper” name.
At first glance, that sounds like a simple and reasonable system. It is meant to facilitate pharmacovigilance and easy, accurate identification of biosimilars, and to avoid inappropriate substitutions.
But stakeholders are urging delay, arguing that implementation costs for reprogramming pharmacy databases, wholesaler databases, and electronic health records could run into the billions of dollars.
Physician knowledge gaps
Prescribing physicians’ knowledge gaps and doubts about biosimilars also need to be resolved, Day and Monroe agreed.
Evidence for biosimilarity includes analytical data, animal study data, clinical studies of pharmacokinetics and pharmacodynamics, immunogenicity, safety and effectiveness, he said.
But the FDA also allows for the extrapolation of indications that were not specifically studied.
“Surveys reveal that physicians do not understand extrapolation,” Monroe said.
Only 12% stated that they trust extrapolation and only 45% said they believe biosimilars will be safe and appropriate for use with their patients.
“Overall there was confidence in the FDA approval process but there are definitely some significant knowledge gaps about that process,” Day noted. “As pharmacists, we have the tools and are uniquely positioned to educate our clinicians and patients with the evidence used to gain approval for biosimilars, and we can help with monitoring to provide reassurance to providers.”
The ability of pharmacists to substitute brand biologics with biosimilars is another factor likely to affect biosimilar sales and uptake.
The BPCIA defines interchangeability as a biosimilar product’s being “expected to produce the same clinical result as the reference product in any given patient,” and for which the risk of diminished safety or efficacy with switching does not exceed the risks of using the reference product without switching or alternation, Day explained.
That is a higher bar than biosimilarity.
Under federal law, biosimilars need not demonstrate interchangeability for FDA market approval but demonstrated interchangeability allows pharmacists to discuss substitution with patients, without involving the prescribing clinician.
But state legislatures have started weighing in on biosimilar substitution at the pharmacy, with state laws requiring that pharmacists contact prescribers prior to any substitutions and allowing prescribers to prevent substitutions with “dispense as written” notations. A total of 27 states and Puerto Rico have passed substitution laws, Day said.
Biosimilar manufacturers oppose these statehouse interventions, arguing that by definition, FDA-approved biosimilars have been deemed safe and the state laws create additional barriers, Day said.
As these issues are resolved and the biosimilar space matures it should bring real cost savings to the specialized pharmaceutical market, as small-molecule generics have done.
“When you have one biosimilar, you have some price competition,” Day noted. “But when you get two or three? Then you have real price competition.”