The Antibody Therapeutic Market
In the last decade, monoclonal antibody therapies (mAbs) have burst onto the field of biopharmaceuticals as the strongest new category of therapeutic. As of November 2020, 88 monoclonal antibody therapies had been approved for clinical use by the FDA; approximately 100 mAb therapies have been approved by a regulatory body globally. In 2018, global sales of antibody therapeutics have topped $122 billion.
Consumer spending on antibody therapies has increased proportionally to sales. The sales of biologic products, the broader category that mAbs fit into, account for 93% of the increase in drug spending by American consumers from 2014–2017. Monoclonal antibody therapeutics themselves are the fastest growing category within biologics — sales grew 90% from 2008–2013. The increase in consumer spending on antibody therapeutics has not gone unnoticed in policy circles. The Biologics Price Competition and Innovation Act was passed in 2010 as a component of the Affordable Care Act in an effort to promote competition and reduce the cost of therapy. It allows for the sale of products that are “biosimilar” to existing therapies; much like the sale of generic versions of the traditional small-molecule therapies.
Monoclonal antibody therapies are made of antibodies, or fragments of antibodies, that interact with a particular protein in a patient’s body to cure or reduce the impact of a given disease. If you would like a primer on antibodies, one of our earliest blog posts is a good summary. Antibody therapies can work in a variety of ways, from directly interfering with protein interactions that contribute to the disease, to recruiting cells from the patient’s immune system to attack diseased or cancerous cells, as well as others.
Traditional drugs are also known as small-molecule drugs, named so because the drug molecules are only tens of atoms large, as opposed to biologics, which are many thousands of atoms large. One reason for the recent explosion of biologics is their ability to interact with protein targets that are typically challenging for small-molecule therapeutics. These include protein-protein interfaces: targets that are featureless and hard to target in the context of small-molecule drugs, but become far more accessible with the use of monoclonal antibodies. In addition, biologics are often far more specific than small-molecules and consequently have fewer off-target interactions that can result in serious side effects. This is born out in practice, with biologics being twice as likely to make it through clinical trials as traditional drugs.
The best selling monoclonal antibody therapy in the market is adalimumab, better known by the brand name Humira, sold by AbbVie. In 2018, Humira generated $19.9 billion in revenue for AbbVie, leading all biopharmaceutical drugs in sales. Humira is an immunosuppressant antibody that is used in the treatment of arthritis, psoriasis, and Crohn’s disease, among others. Of the next nine top selling monoclonal antibody therapies, eight are either immunosuppressants or cancer therapies. Pre-rebate list prices for these therapies are far steeper than for many other drugs, with monthly costs ranging from $2,633 for infliximab all the way to $40,500 for eculizumab, a therapeutic treating a rare disease inflicting only 5,000 patients in the US.
The high cost of antibody therapeutics stems from a number of complex sources. Many mAb therapeutics target diseases with no known cure or therapy and require more research than well-established diseases. Additionally, biologics are more complex to manufacture, transport, and store than small-molecule drugs. As proteins, mAbs are made using living cells such as bacteria, yeast, or mammalian cells, and must be kept in a carefully controlled environment in order to prevent degradation. Antibody therapies that are used for diseases with short treatment durations or with a very small patient population are often priced steeply in order to recoup research and development costs.
However, the pricing of mAb therapies has drawn some scrutiny from organizations such as the Institute for Clinical and Economic Review (ICER). The ICER Annual Report details pricing increases of biopharmaceuticals that are not supported by evidence demonstrating additional benefits for a drug. Monoclonal antibodies have been featured in this report before, including Humira (adalimumab) and Rituxan (rituximab). The pricing of monoclonal antibodies for cancer is under question as well, considering that the cost of treating cancer has doubled in the last decade; monoclonal antibodies used in treating cancer were found to be priced significantly higher than monoclonal antibodies used elsewhere. This can be partly attributed to the implementation of health insurance policy; Medicare Part D plans and private insurance plans in some states must include all cancer therapeutics in their coverage. Since these insurance plans must cover cancer medications at any cost of treatment, there is less market pressure on the therapeutic manufacturers to reduce prices.
Also expected to impact the mAb therapy market was the introduction of biosimilars: molecules that are biologically similar to existing therapies. Intended to provide a cheaper alternative to brand name therapies after the expiration of a patent (similarly to generics for traditional drugs), biosimilars were intended to have a simplified approval process compared to a completely novel biologic. However, due to increased industry representation in the approval process for the Biologics Price Competition and Innovation Act (BPCIA), there are larger roadblocks for the approval of biosimilars than for generics. Biosimilars require additional clinical trials that are not required for generics, which can be challenging to populate because patients already have a treatment option available for their indication. There is a far more complex patent litigation process for biosimilars as opposed to generics, and biologics are protected by large numbers of patents where traditional drugs are primarily protected by a “composition of matter” patent.
The impact of policy details on the adoption of biosimilars can be seen with the drugs Remicade (infliximab) and Humira (adalimumab). The patent for infliximab expired in 2018, and two biosimilars appeared on the market: Inflectra and Renflexis. By the end of the year, biosimilars had captured 10% of the market for infliximab prescriptions, and prices had dropped by 17%. Even though the retail price was lower for the biosimilar Inflectra than the brand name Remicade, intricacies in Medicare reimbursement led to the biosimilar being more expensive for third party payers. In another example, the patent for adalimumab expired in 2016, and although several Humira biosimilars have been approved by the FDA in that time, none are scheduled to appear in the market until 2023. This is in part due to a dense network of patents that surround the original Humira patent that AbbVie has used to increase the uncertainty surrounding patent litigation for potential biosimilars.
Monoclonal antibody therapies serve an important role in the new era of biopharmaceuticals and have the potential to revolutionize therapies for countless diseases. Like with many other facets of healthcare policy, the market for mAb therapies is complex and is subject to a number of intersecting policies. A key priority of all stakeholders should be to allow patients to have affordable access to the astonishing innovations promised by this remarkable class of therapeutics
