Make some space in the medicine cabinet—biosimilars are coming.
The U.S. Food and Drug Administration (FDA) approved the first biosimilar in early March. Three others are undergoing the agency’s review, which is just the tip of the iceberg, as more biologics reach their patent cliff and manufacturers look to develop alternatives in the form of these effective and less expensive medications.
A biologic medicine is a large molecule, typically made from living cells and used in the treatment, diagnosis, or prevention of disease. These medicines generally reduce inflammation and include therapeutic proteins, DNA vaccines, monoclonal antibodies, and fusion proteins.
Physicians prescribe biologics for a wide variety of diseases and conditions, including multiple sclerosis; rheumatoid arthritis; psoriasis; autoimmune illnesses; cancer; and many bone, skin, and joint conditions. Therefore, health care professionals in long term and post-acute care settings will certainly encounter patients using these medications.
Highly complex structures, biologics are often 200 to 1,000 times the molecular size of widely used small molecule drugs—statins (Crestor, Lipitor), antidepressants (Abilify, Cymbalta), and cancer drugs (Gleevec)—and they are highly sensitive, making them more difficult to produce.
The Promise Of Biosimilars
Biologics are very costly, sometimes adding up to thousands of dollars a month—insurance companies typically require patients to pay a percentage of the treatment’s total cost rather than a fixed co-pay. Biosimilars, already a billion-dollar industry, represent a new class of medicines that, in some ways, will mirror the generic drug market, but in many serious ways, will not.
Biosimilars will dramatically alter the treatment options available to physicians and patients. They may represent a shift to a greater number of treatment options, or far fewer, depending on how they are implemented.
By definition and scientifically, biosimilars are not the same as their parent compound because they cannot be copied exactly, like a generic medication. In contrast, generic drugs have the same active ingredient as the brand-name drug and are the same as those brand-name drugs in dosage form, safety, strength, administration route, quality, performance characteristics, and intended use.
Biosimilars are highly similar to the reference product they are compared with, but have allowable differences because they are made from living organisms, such as yeast, bacteria, and animal and human matter. However, biosimilars have no clinically meaningful differences in terms of safety, purity, and potency from the reference product.
The live cells and proprietary process of the original medication cannot be completely replicated. That being said, with expanding demand for good-quality health care, forecasters predict that the safe and regulated introduction of biosimilars into the market will reduce costs and thereby improve access to much-needed medicines.
Biosimilars tend to sell for 20 to 30 percent less than the original biologic, which typically costs about $1,000 to $3,000 a month; even with health insurance, out-of-pocket costs can range to the hundreds or thousands of dollars.
Further, by the simple fact that biosimilars are not exactly the same as their parent compound, they actually represent a new treatment option for some chronic disease patients, such those with multiple sclerosis, HIV, hepatitis C, and rheumatoid arthritis.
Making Biosimilars A Reality
In March 2010, a U.S. biosimilar pathway was signed into law as part of the Affordable Care Act (ACA). The law, known as the Biologics Price Competition and Innovation Act, says that a biological product may be demonstrated to be “biosimilar” if data show that, among other things, the product is “highly similar” and interchangeable with an FDA-licensed product.
In February 2012, FDA issued three draft guidance documents on biosimilar product development to assist the industry in developing them. In 2014, the agency started its review of the first four submitted applications, leading to the approval of the first biosimilar, Zarxio (filgrastim-sndz), a biosimilar of the cancer drug Neupogen (filgrastim). Neupogen is designed to increase white blood cell counts and lower infection rates, mostly in patients getting chemotherapy and other treatments.
Despite access expansion and cost-saving potential, patient safety remains the top priority in health care. A double-edged sword exists with these medicines—while they reduce inflammation, they also suppress the immune system, possibly placing its users at increased risk of infections, cancers such as lymphoma and skin cancer, liver failure, and turberculosis.
Again, biosimilars do not exactly mimic their reference products; therefore, as they become available, health care professionals and patients will have to closely monitor their usage to be alert for adverse reactions and treatment effectiveness.
Other questions also arise as biosimilars become available related to how broad their usage will be, their actual labeling, and who will benefit from potential cost savings.
Transparency, Communication Needed
One positive step forward is to advocate that FDA label each new biosimilar with a distinguishable name to improve pharmacovigilance efforts, which depend upon the ability to identify which product a patient received. Because these products are not scientifically the same as the original, they should not share the same name, scientists note. While FDA seems to be leaning toward distinguishable names, as evidenced by the “-sndz” tag attached to Zarxio’s chemical name, which stands for the company that makes the medicine, Sandoz, in Princeton, N.J., the actual policy is not finalized.
With one FDA-approved biosimilar poised to hit the market soon and several others currently under review, FDA regulations are needed.
Second, FDA has a pathway for approving “interchangeable” biosimilars, but the process and clinical requirements for determining how closely a biosimilar matches the original biologic hasn’t been fully tested. In fact, Zarxio was specifically approved as not interchangeable. (In this case, significant data, particularly from Europe, pointed to its safety and efficacy.) If a biosimilar is not interchangeable, then providers (and patients) need to be extra vigilant in monitoring.
Feds Pass Baton To States
That’s why transparency and communication are key. While FDA is in charge of approving new medications, it’s actually up to the states to regulate their access via pharmacy boards and state legislatures. In 2015, 12 states are considering legislation that will establish a framework of regulations under which biosimilars can be introduced to patients.
The key issue is whether pharmacists must notify providers and patients if/or when insurance companies request an automatic substitution of a biologic for a biosimilar. Clearly, a patient-centric policy would require notification to physicians and patients to maintain open lines of communication. As more biosimilars enter the U.S. market, physicians and patients must protect their independence in the decision-making process and monitor the payer landscape for barriers that payers may institute in an effort to reduce cost.
For example, one such barrier is a “fail first” policy where insurance companies encourage a “preferred” (less expensive) first-line medication for patients with a specific diagnosis, which may lead to higher co-pays should patients (and their physicians) want to be maintained on a previously effective medication.
Cases In Point
In Colorado, new legislation (signed into law in April) requires that pharmacists notify providers about a switch within a reasonable period of time.
The Global Healthy Living Foundation, in Upper Nyack, N.Y., an advocacy organization for people with chronic illnesses, worked with a volunteer patient advocate who testified to her legislators about why biosimilars are a welcome option for patients, but only when the decision to use them is made between the patient and the provider. Her testimony and that of other stakeholders led to House Bill 71 being passed.
On the opposite side of the spectrum, in Oregon, legislators have introduced a bill that seeks to require pharmacists to substitute interchangeable biologics without communicating with the physician or making information accessible regarding the product dispensed to the physician. Further, the Oregon bill seeks to repeal existing law that requires pharmacists to inform patients when they are making a substitution of a drug their physician prescribed.
Colorado and Oregon are just two of the states determining health policy for patients. There is a wide variety of language under debate, and outcomes are uncertain.
Patient Safety First
The safe and regulated introduction of biosimilars into the market has been forecasted to increase access while reducing costs, potentially paralleling how generic drugs cost significantly less compared with brand-name drugs when they have been automatically substituted. That’s why some payers will be eager to switch patients to biosimilars as more of them get approved.
However, in the case of biologics and their biosimilar mimics, the situation is different. Even the slightest difference between a biosimilar and the biologic it copies—whether in the manufacturing or even the handling process—could have a significant health impact on patients.
At issue is if physicians are kept in the dark about which medications their patients receive, they can’t treat adverse events or reactions, or even monitor how a patient responds to specific treatments. Further, if patients don’t know that the medication their physicians intended for them has been substituted, they will not be able to accurately report an adverse reaction.
While the projected affordability of biosimilars means that they hold promise for patients who need access to critical treatments, there is a need to put patient safety first.
Jonathan Krant, MD, FACP, is chief medical officer at the Global Healthy Living Foundation, www.GHLF.org, and section chief of rheumatology at Adirondack Health. Krant can be reached at jkrant@ghlf.org.