by Steve Rudner, MS, PharmD
Director Pharmacy Network Contracting
Long before the business of commercially available pharmaceuticals was globalized, mankind utilized naturally occurring products to improve health and alleviate symptoms. For example, the use of honey as an anti-infective agent or the chewing of willow bark to relieve pain and fever can be ascribed to as early pharmacotherapy. In essence, the philosophy of using an outside agent to augment patient treatment has not changed over hundreds or thousands of years. What has changed is the use of modern technologies and modalities for not only manufacturing new drug therapies but recognizing their unique mechanisms of action and the potential for the mitigation of disease states once thought untouchable.
One of the more recent advancements with respect to pharmaceuticals has been truly transformative to the management of disease is the discovery and utilization of “monoclonal antibodies” (mAb). This is an innovative and unique type of pharmacotherapy that differs from conventional drug therapy in many aspects; including the mechanism of action, drug nomenclature, disease state foci, and even the logistical and operational challenges associated with this type of treatment. The impact of mAbs cannot be overstated. Currently, of the top five drugs in terms of spend sold in the U.S., three are mAbs. mAbs are also playing critical roles, in addition to vaccines, in the fight against COVID-19.
These mAbs are man-made proteins from B-cells that are targeted toward specific antigens. Different monoclonal antibodies can be synthesized from numerous sources, but every unique monoclonal antibody originates from a single parent cell to produce a homogenous antibody (i.e. a consistent biologic drug). This homogeneity facilitates the targeted therapy of the specific monoclonal antibody because all of these synthesized molecules “attack” the same specific section on its target. The significant point here is that mAb therapy is directed at a specific type of antigen targeted, as opposed to more standard antibody therapy, such as that which occurs through plasma donation. Naturally occurring antibodies can target all types of antigens. mAbs are precise in their actions, which improves their efficacy and helps minimize adverse events.
After attaching to the antigen, there are multiple immune system modifications that may be facilitated by the mAbs. Some mechanisms of action that mitigate disease states include (but are not limited to) the identification of malignant cells that result in a more robust immune system response, the obstruction of disease cell growth , direct attack on the disease cells themselves and even the transport and piggybacking of radiation or chemotherapeutic treatment to cancer cells while minimizing the exposure to healthy, non-affected cells.
As with many pharmaceuticals, the names of mAbs seem excessively complicated and hard to comprehend or pronounce. However, the nomenclature for mAbs is very deliberately structured and conveys a lot about the molecule. Although all mAbs end with the suffix “mab” in the name, the substem(s) that precede this suffix (or stem) (-mab) will identify the body subsystem that is being treated and identified the source of the protein synthesis (before 2017). For example, rituximab indicates action on a “tumor” (tu) and a chimeric (xi) source, chimeric meaning the mAb contains components from two different specific (e.g. mouse and human). The prefix (rit) is individualized in the case of not only rituximab, but the other approved and authorized mAbs. After 2017, the second substem identifying the source of the protein was eliminated from the nomenclature guidelines.
There is no “typical” disease state or ailment that these agents treat; and those that are treated can be classified as illnesses that are serious and many times, life threatening. Multiple cancers (solid tumor as well as blood borne) and autoimmune diseases (rheumatoid arthritis, multiple sclerosis, psoriasis) are several of the most well known categories of maladies that are treated by mAbs. These drugs can also treat cardiovascular ailments, gastrointestinal diseases (ulcerative colitis, Crohn’s) and several more diseases including viral conditions.
Recently, there have been multiple mAbs that have earned an Emergency Use Authorization (EUA) in the treatment against COVID-19. As a reminder, an EUA is issued when the Secretary of HHS authorizes an unapproved product OR an unapproved use of an approved product to diagnose, treat or prevent a serious disease. In late 2020 and early 2021, mAbs from Eli Lilly and Company as well as Regeneron were granted an EUA for the treatment of mild to moderate COVID-19. Lilly’s two mAbs are bamlanivimab and etesevimab and the Regeneron agents are casirivimab and imdevimab. All of these mAbs neutralize the “spike protein” of the SARS-CoV-2 virus by binding to it. This prevents the spike proteins from binding to the receptors that trigger an infection, the ACE2 (angiotensin converting enzyme 2) receptors. Learn more about expedited drug reviews in the time of COVID on Vizient’s VerifiedRX podcast.
Logistically, there are several challenges stakeholders must consider when considering appropriate treatment with mAbs. The drugs are given are almost exclusively by injection or infusion; therefore, the site of care must be chosen carefully and be appropriate for not only the infusion itself, but pre and post infusion care. mAbs are most frequently dispensed from either the health care site itself (i.e. hospital or ambulatory site) or what is known as a “specialty pharmacy” for delivery direct to the patient with administration by a health care professional. Lastly, because of the high cost of the majority of these agents, the patient and their provider must evaluate the method of payment, which will most likely always include a third-party payer, to understand if the treatment will be covered.
In summary, mAb therapy is another evolution of pharmaceutical therapy that continues to improve upon previous iterations of drug choice and treatment. This therapy is a very targeted treatment of specific life threatening and deleterious disease states. Monoclonal antibody therapy continues to develop as research determines that additional disease states can be mitigated by the innovative type of treatment. It’s quickly becoming a MAb, MAb, MAb, MAb world.
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