Biosimilars

Key points

Introduction

The development of biosimilar agents such as tumor necrosis factor (TNF) inhibitors has significant potential to change the standards of psoriasis therapy in forthcoming years. The availability of biologic drugs for the treatment of moderate-to-severe psoriasis has revolutionized psoriasis treatment, and, as the patents for these medications (adalimumab, etanercept, infliximab) are expiring soon, dermatologists can expect increased advocacy for biosimilars.

The development of biosimilars is not the same as developing a generic, in part because biologics are so much more complex than small molecule drugs. Biologics are so complex that no company can duplicate them, not even the originator company. Each batch of an innovator biologic may differ in small ways from other batches. Variation within an innovator product occurs and is acceptable as long as it is not thought to have clinical implications. Similarly, biosimilars are not identical to the innovator product but can be marketed if the differences between the biosimilar and the innovator are sufficiently small that no clinical implications are expected. An extensive array of data is required to demonstrate biosimilarity (more data than are required of batch-to-batch variants in the innovator product).

The Biologics Price Competition and Innovation (BCPI) act was created as a part of the Affordable Care Act in 2010 as an abbreviated licensure pathway for biologic products that were “biosimilar” to, or interchangeable with, the original biologic product. Through the BCPI act, the US Food and Drug Administration (FDA) has defined a biosimilar as a biologic product that is highly similar to the original product notwithstanding minor differences in clinically inactive components. No clinically meaningful differences between the biologic and the biosimilar in terms of safety, purity, and potency can exist. These aspects of the biosimilar drug must be demonstrated through analytical studies, animal studies, and at least 1 clinical study, unless the FDA deems it unnecessary. The biosimilar, however, does not need to demonstrate its independent efficacy and safety for FDA approval, as is typically required for the original biologic off which it is modeled.

The greatest potential for biosimilar agents in the treatment of psoriasis is in association with TNF inhibitors (infliximab, etanercept, and adalimumab); however, many clinical trials investigating these biosimilar agents are currently in the preliminary stages and results have yet to be published. An infliximab biosimilar by the brand name of Inflectra was recently approved in April 2016 by the FDA for the treatment of adult severe plaque psoriasis, adult and pediatric moderately-to-severely active Crohn disease unresponsive to conventional therapy, moderate-to-severe rheumatoid arthritis in combination with methotrexate, active ankylosing spondylitis, and active psoriatic arthritis.

Small molecule generic drugs

In approving a generic drug, the FDA requires pharmaceutical equivalence to the reference drug (identical amounts of same active drug ingredient in the same dosage form and route of administration), bioequivalence to the reference drug, and adequate labeling and manufacturing. Bioequivalence is generally used to establish similarity between a generic drug and reference drug and is defined as the absence of significant differences in the availability of the active ingredient at the site of drug action. Two drugs are bioequivalent if the 90% confidence intervals (CIs) of pharmacokinetic parameters (maximum concentration, area under the curve) of generic-to-reference drug ratios fall within 80% to 125%. This bioequivalence ensures that the rate and extent of absorption of the generic drug does not differ from the reference drug.

Generic drugs approved by the FDA have the same high-quality, strength, purity, and stability as the reference drug. In addition, the generic manufacturing, packaging, and testing sites must pass the same quality standards as those of brand name drugs.