Biologic products are drugs that have regulation by the United States Food and Drug Administration. They have utility to diagnose, prevent, treat and cure medical diseases and conditions. They are usually large and complex molecules and are harder to characterize than small molecule drugs. Common and familiar biologics include etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), etc.

Biosimilars are products which are highly similar to and have no clinically meaningful differences from an existing FDA- approved reference biologic. All biosimilars are prescription drugs which means you cannot get them without an appropriate health care providers prescription.

How does a Biosimilar Function?

Approved biosimilars are made of biologic materials and are highly similar to a drug that is already approved, widely tested and prescribed. To gain approval, biosimilars must go through an extensive array of tests and clinical studies for assessment of safety, purity and potency. This is typically derived from data including:

• Analytical studies demonstrating that the biological product is highly similar to its reference product;

• Animal studies, including assessment of toxicity; and

• A clinical study or enough studies to demonstrate safety, purity, and potency of the proposed biosimilar product in one or more of the indications for which the reference product is licensed. This typically includes assessing immunogenicity, pharmacokinetics (PK), and, in some cases, pharmacodynamics (PD) and may also include a comparative clinical study.

Although Biosimilars undergo an abbreviated track to FDA approval, the drug undergoes rigorous testing before approval and entering the market. When reviewing the licensure for a biosimilar, the FDA will review the data and information as a whole. It should be noted that if a biosimilar is approved for one indication of its brand name biologic, then all the indications of the brand name are approved for the biosimilar as well.

How are Biosimilars Named?

Biosimilars are given names that are able to tell you what its reference drug is. The drug name is followed by a four-letter suffix (or tag) that tells dictates the version of the drug. For example, infliximab (Remicade®) has two biosimilars on the market, Inflectra ® (infliximab-dyyb) and Renflexis ® (infliximab-abda). The ending tag allows doctors and pharmacists to identify which biosimilar is being used.

Are Biosimilars the same as Generic Drugs?

Biosimilars and generic drugs are similar in many ways. They are both versions of existing brand name drugs that are more affordable and therefore more available to patients. Additionally, they both are approved through a process that avoids conducting costly clinical trials.

However, there are slight differences between biosimilars and generic drugs. Generic drugs have the same active ingredients as their respective brand name drug. Also, generic drugs must be deemed bioequivalent to the brand name drug by the manufacturer.

On the other hand, biosimilars are required to be highly similar, but not identical to their reference products. Manufacturers of biosimilars must be able to demonstrate that there are no meaningful clinical differences between the biosimilar and its reference biologic. This is particularly important in regard to safety and effectiveness.

What Biosimilars Exist in the Market?

As of December 2020, there are 29 biologics approved for use in the United States and only 21 of those are available for use in the market currently. The therapeutic areas that biosimilars are focused in include oncology, immunology, hematology, metabolic disorders and musculoskeletal disorders. Leading companies profiled in the U.S Biosimilars Market are:

• Novartis

• Mylan N.V.

• Coherus BioSciences, Inc.

• AbbVie Inc.

• Pfizer Inc.

• F. Hoffmann-La Roche Ltd.

• Eli Lilly and Company

• Teva Pharmaceutical Industries Ltd.

• Celltrion Inc.

• Amgen Inc

The “Purple Book” is available as a searchable, online database. It contains information about all FDA-licensed biological products regulated by the Center for Drug Evaluation and Research (CDER). This includes biosimilar and interchangeable biological products as well as all FDA-licensed biological products regulated by the Center for Biologics Evaluation.

The Lasting Impact on the Healthcare Landscape

Biosimilars are drugs that are made to be copies of existing biologics. Many existing biologics are meant for patients that are suffering from life-threatening and chronic diseases. This means that patients not only need their medication, but that it may be the only medication that currently exists in the market to treat their condition.

The problem is that biologics are expensive. A single dose may cost $10,000 or more. Although insurance policies will cover most of the cost, the patient must overcome the hurdles of utilization management and prior authorization.

Certainly, there is a large impact on overall health care costs when taking biologics. Therefore, manufacturers of biosimilars have made their drug prices lower than its reference biologic. The use of biosimilar products enables patients to access more affordable treatments, as they cost up to 30% less than their reference products. Thus, this allows healthcare systems to make significant cost savings. In theory, this should mean that the patient will save money taking a biosimilar over its reference product. However, this is not seen in practice because insurance companies and pharmacy benefit managers have not yet passed on these savings to the patient.

Additionally, biosimilar products undergo utilization management despite the cost savings. Prior authorizations and step therapy requirements are in full effect. In some cases, require failure of the biologic reference product prior to treatment with the biosimilar.

The Future of Specialized Medicines

Biosimilars are currently the fastest-growing class of therapeutic products in the United States. As reported in The Economist, biologics and their respective biosimilars could encompass over 30% of total big pharma sales by 2023. Because the existing patents for almost 20 biologics will expire, it opens the market to more biosimilar products.

The pipeline from 2021 to 2025 contains at least 5 approved biosimilars to adalimumab and potentially 4 others all of which could launch in 2023. Additionally, there are 14 other potential products with other reference products. According to the United Nations, by 2030 the proportion of global deaths due to chronic diseases is expected to increase to 70% of total deaths. The rising prevalence of chronic disease such as arthritis, asthma and cancer is a major driver of the specialized product market.

Educating providers, pharmacists, patient groups and health plans about the possibilities and opportunities that exist in the biosimilar landscape is crucial to increased access of these products. Increased uptake is necessary for more biosimilars to make way into the market. Widespread adoption would improve the health of the American public.

The assistance of Ashley Varghese, PharmD candidate 2021 is gratefully acknowledged in the preparation of this article.