The next 12–18 months could be a critical time for biosimilars in the United States (1). This product class has grown rapidly since passage of the Biosimilars Price Competition and Innovation Act (BPCIA) of 2010. That landmark legislation allowed for biosimilar market approvals based on previously approved “reference products,” creating an expedited pathway that reduces biosimilar development costs and speeds regulatory review so patients get faster access to essential medicines. Increased competition from biosimilars could save the US healthcare system billions of dollars. Both regulators and the judiciary are now revisiting important aspects of BPCIA, and their decisions will help determine the full market potential of this product class.

Regulatory Questions
In March 2015, the US Food and Drug Administration (FDA) approved its first biosimilar product, more applications have been filed, and companies are investing heavily in development. Against this backdrop, the FDA is considering several key questions regarding implementation of the BPCIA.

Interchangeability: One key issue is how to determine whether a biosimilar is “interchangeable” with its reference product. Under the BPCIA, the FDA deems a biologic to be biosimilar if it is demonstrated to be highly similar to (without meaningful clinical differences from) a reference product. A biosimilar also can be deemed “interchangeable” with the reference product if (among other things) it produces the same clinical effect. Interchangeable biosimilars would be covered under state automatic-substitution laws, under which pharmacies would be required to fill reference-product prescriptions with less-expensive biosimilars, dramatically increasing patient access to critically needed medicines while lowering healthcare costs.

The FDA is developing regulatory criteria for proving interchangeability (e.g., whether the proof must include data from expensive clinical trials). Many stakeholders have argued that this process is moving too slowly, thereby impeding development of a robust biosimilars market. The agency says that it must get the science right at this early stage in biosimilar regulatory history. Final guidelines will help determine the developer’s cost of obtaining an interchangeability designation — and thus the real economic incentives for companies to develop biosimilars.

Nomenclature: Another key issue is whether biosimilars should have the same international nonproprietary name (INN) as their reference products. The BPCIA’s silence on this issue has led to much debate. Supporters of unique INNs (e.g., the branded biologics industry) argue that biosimilars should have different names because they are similar but not identical to reference products. Different names thus would ensure proper pharmacovigilance. Advocates for the same INNs (including the biosimilars industry and pharmacists) argue that differential naming would quash competition and cause confusion among prescribers, patients, and pharmacists — potentially compromising safety. Given other available tools, supporters of same INNs say, effective drug-safety monitoring wouldn’t be compromised.

The FDA has proposed adding distinguishing suffixes to the INNs of both originals and biosimilars. Interchangeable products would share the same suffix. The agency believes that “shared nonproprietary names are not appropriate for all biological products.” It sees a need to clearly identify different biologic products for pharmacovigilance and to differentiate among noninterchangeable products.

The proposed rule has received much comment and criticism, including from the Federal Trade Commission, which cautions that prescribers may be reluctant to prescribe biosimilars with unique INNs because of misperceptions that different names imply clinically meaningful differences between the biosimilar and reference product, thereby hampering competition. It remains to be seen whether/when the FDA will issue a final naming rule or guidance — or whether that will be challenged in court.

the Patent Dance The courts are already interpreting other aspects of the BPCIA, such as whether certain steps in the statute’s patent-dispute resolution procedures are mandatory or voluntary and what remedies are available to parties that do not take certain steps under those procedures. One such “patent-dance” step requires a biosimilar applicant to give 180 days of advance warning that it intends to commercially market a biosimilar. Last year, the US Court of Appeals for the Federal Circuit held that such notice could be given only after FDA approval of a biosimilar and that notice could be compelled by the reference product’s sponsor through an automatic injunction.

Sandoz, the biosimilar manufacturer in that case, has asked the US Supreme Court to review the decision. It argues that Congress did not intend for the notice provision to cause a sixmonth delay in patient access and that an automatic injunction conflicts with remedies Congress did intend. (I have filed amicus briefs in support of Sandoz’s position on behalf of biosimilar trade associations.) Whether the Supreme Court reviews the Federal Circuit’s decision — and if so, whether it reverses the decision — will shape the biosimilars landscape for years to come.

Reference
1 Angulo C. Biosimilars Market Is at a Critical Turning Point. National Law J. 21 March 2016.

Carlos Angulo is a partner at Zuckerman Spaeder LLP, 1800 M Street NW, Suite 1000, Washington, DC 20036-5807; 1-202-778-1800; www.zuckerman.com. This piece is adapted from the longer article referenced above.