Lauren Santye, Assistant Editor, Specialty Pharmacy Times

*This article was originally published by the 

Amgen has released the fourth edition of its 

, which addresses key challenges that need to be overcome for the widespread uptake of biosimilars in the US market.  

“As the biosimilar market grows in the US, all stakeholders will assess this new category of medicines with a focus on driving value-based healthcare, which includes delivering quality of care, effectively managing cost and achieving intended patient outcomes,” the authors of the report wrote. Most surprisingly, for Medicare patients who are still in the coverage gap, a biosimilar product could cost the patient more out-of-pocket than the originator drug. This is because biosimilars are lumped together with generics in Medicare reimbursement policy.  

Other challenges facing biosimilars include disputes about the interpretation of certain provisions of the Biologics Price Competition and Innovation Act (BPCIA). Litigation has become a common occurrence for many biosimilar applicants. In fact, a single infringement lawsuit by the reference product could delay a product launch, or a biosimilar applicant may decide to launch at-risk, according to the report.  

At-risk launches mean that patent ownership issues remain unresolved, even as the products are being dispensed. These launches may result in the withdrawal of a product from the market and/or royalties for the reference product sponsor at the end of the lawsuit. Three of the 4 FDA-approved biosimilars are currently involved in lawsuits as of January 2017. Two of the biosimilars on the US market were launched at risk, according to the report.  

Six more products have active fillings with the FDA that are expected to be acted on in 2017.  Issues that payers and other formulary decision-makers should take into consideration when evaluating a biosimilar are product considerations, manufacturer considerations, and operational considerations. Product considerations include extrapolation; curative treatment versus supportive care; product dosing; delivery device, formulation, and handling; and distribution channels. Manufacturer considerations are supply chain reliability and patient support programs. Lastly, operational considerations include pharmacovigilance, pricing and contracting, reimbursement, and information technology.  

Both patients and physicians have expressed unfamiliarity in whether a biosimilar can be used in all the same indications as the reference product. A 2016 survey by the Biosimilars Forum found that only 12% of respondents reported being completely comfortable with the concept of extrapolation. Post-marketing surveillance and data from observational studies may help address concerns around extrapolation, according to the report. In the United States, the first 4 approved biosimilars received approval for all available indications; however, some indications may be initially excluded from an approved biosimilar’s label because of established exclusivity periods by the FDA.  

The use of biosimilars in certain clinical settings is also important to consider. In oncology, utilization of biosimilars may depend on whether the drug is administered for supportive use or with curative intent.   Biosimilars could be available in several forms, and physicians, pharmacists, nurses, patients, and caregivers need to be aware of differences in indications, corresponding doses, and dosage forms between the branded reference product and the biosimilar.

 “Longer-term, what happens as more biosimilars for the same reference product become available?” the authors wrote. “What if each one has its own particular packaging that differs from that of the reference product? The question then becomes more complex: how may differences can a market accommodate and how many ‘highly similar’ products will have nonclinical differences that need to be noted and tracked in electronic systems?”  

How a manufacturer chooses to employ delivery methods is also a challenge. The manufacturer’s choice of delivery device for a biologic drug can make a difference in the patient’s compliance and adherence. Some manufacturers have already chosen to use delivery devices that differ from the biosimilar’s reference product. Patients and healthcare professionals will require adequate education regarding the different devices and their proper use and handling, according to the report.  

Formulation is another potentially important point of differentiation, the report noted. Distributors and health care professionals who administer biosimilars need to know of and take precaution when dealing with differences between biosimilar storage, handling, and route of administration with the reference product. 

For biologics launched in recent years, specialty distribution has been used more frequently. The specialty channel could enhance the efficacy of biologics distribution, with respect to issues such as product storage, cost and delivery, product dating, and inventory management. Supply chain reliability is an important manufacturer consideration. Disruptions to drug supply is becoming a common occurrence, especially for oncology drugs, the authors noted. To avoid treatment delays, the report said it’s important to consider the robustness of the manufacturer’s supply chain when evaluating biosimilars. The manufacturer’s history of shortages and recalls related to quality concerns should also be considered, and an evaluation of their ability to maintain adequate production and stock to support the demand.  

In recent years, drug shortages have gained attention as a common occurrence due to their highly-specialized manufacturing process. Furthermore, sterile injectables account for a large percentage of these shortages. Although the number of new shortages have decreased overall since 2011, the number of ongoing shortages remains high. These shortages can cause serious logistical, ethical, and financial issues, and could potentially lead to a variety of other health and safety issues.  

“It’s horrible and incredibly challenging when you experience drug shortages,” a pharmacy director and editorial council member said in the report. “In oncology, for example, if there isn’t an alternative you have to look at intensive treatment versus curative or supportive and determine if any patients can discontinue treatment early.”  

Patient support programs are crucial for patients and can influence the behavior of physicians or serve as a point of differentiation between biosimilars. Biosimilar manufacturers will likely consider providing meaningful patient support services as part of their value proposition to meet the needs of patients and providers.  

Pharmacovigilance—tracking and monitoring of drug safety over time&mdash;is especially important for biologics and biosimilars to detect any emerging safety signals, the authors wrote. To help facilitate pharmacovigilance, the FDA released final guidance on nonproprietary naming of biologics in January of this year. Biologics can be covered under the medical benefit or the pharmacy benefit, according to the report. Self-administered medicines are typically covered under the pharmacy benefit, while injections of infusions that are supervised by a physician are typically paid for as medical benefits.

Key differences between the 2 payment systems, from the payer’s perspective, is that specialty drugs covered under the pharmacy benefit are reimbursed based on their national drug codes (NDCs). The NDC codes enable anyone to analyze the use of that medicine to track utilization and know the drug, manufacturer, strength, and package size.

Under the medical benefit, specialty drugs are commonly tracked and reimbursed using the Healthcare Common Procedure Coding System (HCPCS) codes, which identify the drug’s chemical name, but not the manufacturer, the strength, or package size. Biosimilar products that appear under the same HCPCS codes under Medicare Part B will be issued and assigned modifiers that help identify the manufacturer of the product and distinguish between biosimilar products that are made by different manufacturers. Through the modifiers, CMS will have the ability to track claims payment and develop a better understanding of the use of biosimilars in Medicare Part B.   

The expected trend in biosimilar utilization versus the originator product may be a proxy for biosimilar adoption, according to the report. To create a sustainable biosimilar market, an ongoing commitment to driving competition is required.  

“As 2016 drew to a close, there were 4 approved biosimilars and 6 active filings pending FDA review in 2017,” the authors wrote. “Simultaneously, US regulatory bodies committed necessary resources to support the review of biosimilar applications as they continue to form final guidance around the biosimilar path-to-market.  

“The events that unfold in 2017 may increase experience and understanding of biosimilars, which in turn could increase confidence and utilization of these medicines in the US. Limited exposure to biosimilars in the US has resulted in the cautious uptake of biosimilars and identified knowledge gaps impacting downstream user trust in these products.”  

A 2015 study in Europe, however, found that 40% of surveyed physicians had increased confidence in the use of biosimilars compared with 3 years ago. The study suggests that gains in clinical experience could help reduce hesitation regarding biosimilar use in the United States.  

Discussions carried out among health care professionals, administrators, regulators, manufacturers, and patient groups, regarding the experiences of early adopters could help facilitate acceptance, according to the report. Building confidence in this treatment space will remain a primary goal for the industry in 2017.  

Legalities may also pose a significant challenge for manufacturers who are attempting to bring biosimilars to the market in 2017.  

“Likewise, court decisions on complex issues regarding patent protection and data exclusivity that are review in ongoing litigation between biosimilar manufacturers and reference product manufacturers will likely inform future decisions on applications and launch strategies for biosimilar manufacturers,” the authors wrote.  

Lastly, uncertainty surrounds the future of the Affordable Care Act—–and as a result the BPCIA––under the new administration. But repealing the legislation could have implications for several regulations that affect biosimilars, including the Medicare Part D Coverage Gap Discount Programs, the “deemed to be a license” provision, and the regulation freeze, the report concluded.

Lauren Santye, Assistant Editor, Specialty Pharmacy Times

Multiple Challenges Predicted for Biosimilars in 2017