Patients Save Big with Generic Medications. Can Cancer Patients Do the Same With "Biosimilar" Drugs?

The Ever-Increasing Cost of Cancer Care and a Quest for Solutions

A lot of patients ask us, “can I be on a biologic drug, instead of the name brand?” Doctors say the answer is sometimes, but definitely not always.

The cost of cancer care can be staggering for many people. While drugs provide a huge amount of value to patients, overall they make up less than 20% of the entire cost of healthcare in the country. Still, the cost of drugs gets a lot of attention. Popular immunotherapy medications used to treat a variety of cancers can cost almost $175,000 per year per patient. The manufacturers argue that they take the risk of development, investing for years, and most of their bets fail. The argument is that drug prices reflect this reality. Regardless, some physicians and advocates believe there is a very real need for medications that may be just as efficacious as formally approved drugs, without the hefty price tag. Biosimilar drugs could be part of the solution, especially for drugs that have gone off patent and can lawfully be copied.

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Biologic Drugs and their Sources

Biologic medications are derived from living organisms or their products, such as blood and proteins. There is no one structure to a biologic drug, but they can be composed of any combination of proteins, sugars, DNA, and even intact cells. Due to this complexity, their exact structure may not even be fully known. The donor organisms from these drugs can be human beings, animals, and microorganisms, like bacteria.

"A biologic is anything that is produced by a cell. Cytokines, interleukins, monoclonal antibodies… are all examples of biologic therapies," says Dr. Jennifer Johnson, a medical oncologist, and an associate professor at the Sidney Kimmel Cancer Center at Thomas Jefferson University. Cytokines and interleukins are small molecules that cells use to communicate with each other. Antibodies are produced by the immune system to fight infections.

The process to produce biologic drugs can be as complex as their structures. This is distinct from routine pharmaceutical drugs that can be easily and precisely mass-produced by pharmaceutical companies. A biologic drug may only be produced by its parent organism under very specific circumstances, such as a narrow range of temperature, pressure, humidity, et cetera. Once produced, the process of purifying it could be very tedious as well. Any changes to this manufacturing process can result in a drug that does not have the intended therapeutic value.

All in all, biosimilar drugs are hard to produce, and even harder for other pharmaceutical companies to replicate.

Biosimilar Drugs: It's in the Name

Biosimilar and Interchangeable Products

The key to understanding biosimilar drugs is to decipher their name. These drugs are like known biologic drugs, called reference products, but are not exact duplicates of them. Clinically, both reference and biosimilar drugs are similarly effective, safe, and pure.

"Due to the nature and complexity of biologics, it’s really difficult to manufacture exact reproductions (like oral generics), so biosimilars were developed," says Dr. Rose DiMarco, Clinical pharmacy specialist for oncology at the Sidney Kimmel Cancer Center at Thomas Jefferson University.

In the words of the FDA, "A biosimilar is a biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product."

Manufacturers of biosimilar products must demonstrate that their products are "highly similar" to the reference drugs. This includes comprehensively analyzing the structure, function, and effectiveness of the intended reference and biosimilar drugs. The clinically active components of both the reference and the biosimilar must be identical. However, clinically inactive components of the two drugs can have minor differences. Thus, the biologic needs to be highly similar to the reference drug but not identical.

Biosimilar Development, Review, and Approval

In addition to establishing structural similarity, manufacturers need to additionally demonstrate that their biosimilar and reference drugs are not clinically meaningfully different. The FDA elaborates, "A manufacturer must also demonstrate that its proposed biosimilar product has no clinically meaningful differences from the reference product in terms of safety, purity, and potency (safety and effectiveness). This is generally demonstrated through human pharmacokinetic (exposure) and pharmacodynamic (response) studies, an assessment of clinical immunogenicity, and, if needed, additional clinical studies."

Biosimilars & Generic Drugs: Similar Yet Different

Biosimilar drugs have been understandably but erroneously compared to generic drugs. While there are certain similarities between the two, there are many important differences as well.

Dr. DiMarco elaborates, "In some ways, biosimilar and generic drugs are similar. The FDA approves biosimilars under a special process and allows for small differences that don’t amount to clinically meaningful differences."

What’s the difference? Biosimilar and generic drugs

Generic drugs are produced through chemical processes and are compounded to be identical in their structure to their costlier, branded counterparts. They usually emerge after the patent, which allows a company exclusive right to manufacture and sell their drug under a brand name, expires. Since branded drugs are chemical compounds, it is relatively easy for a competitor to figure out their structure and duplicate it. Thus, the therapeutic effects of the generics are identical to the branded ones, but the former retail for much cheaper prices.

Generic Drug Facts

Biosimilar drugs are "similar" to generics because they mimic the therapeutic effect of the brand-name biologic without the hefty price tag. However, the process of making a biosimilar drug, as detailed above, is complex and does not deliver a product that is identical to its reference drug, in contrast to generics.

Dr. Johnson proclaims, "The amount of research and development that you must put into making a biosimilar drug is far greater than that required for a generic drug. Moreover, the complexities in the manufacturing process are likely far greater for biosimilars too. Unlike generics, you cannot just combine chemical A and chemical B and heat it to a certain temperature and voilà… you have the drug. The methods to creating biosimilars are more complex and nuanced."

Another reason biosimilar drugs differing from biologic ones is that their manufacturers usually do not have access to the same cell lines and are not privy to the fine details of the manufacturing process used to produce the biologic drug. "Such data just isn't publicly available," says Dr. Johnson.

Quality Control for Biosimilar Drugs

The FDA has very exacting requirements for biosimilar drugs before they approve them for clinical use. The burden of proof rests on the manufacturer.

Biosimilar Development, Review, and Approval

They must provide evidence that their product has the same mechanism of action, strength, and dosage as the reference drug. Their route of administration, such as oral or IV, must also be the same as the reference drug. Additionally, they must prove that their product does not meaningfully differ from the original drug. They should also ensure that their manufacturing process is of the highest standard. All of this is done through scientific studies and data, which could come from laboratory, animal, or clinical studies.

The FDA has approved only 39 biosimilars to date, many of which are used for cancer treatment. This includes drugs like rituximab (brand name Rituxan), used to treat blood cancers, and trastuzumab (brand name Herceptin), which is a widely popular treatment for breast cancer.

The FDA also has an interchangeable product designation. This label requires proof beyond that required for highly similar biosimilars. Interchangeable biosimilar drugs must mimic the exact same clinical result as their reference product. Switching or interchanging one product for the other would not change the safety and risks for the patient in any way.

The Difference Between an Interchangeable Biosimilar and One That Isn’t

As of October 2022, only three drugs none of which are cancer medications have been designated interchangeable. This includes an insulin product, a Coherus biosimilar ranibizumab-eqrn (brand name Cimerli) use to treat retinal diseases and Adalimumab-admb (brand name Cyltezo), a monoclonal antibody based on the Humira used to treat inflammatory conditions.

Biosimilars vs. Biologics: Advantages and Concerns

The current state of biosimilars in practice

One major advantage of biosimilar products is that they are less expensive than branded biologics. "Cost is probably one of the biggest incentives for companies to produce such drugs," says Dr. Johnson.

Additionally, since they are modeled after biologic products with benefits demonstrated via clinical trials, they themselves do not need to be tested in time-consuming and costly trials. This means that they can be expedited into day-to-day clinical medicine much faster than the original biologics. It is important to note that they offer no therapeutic advantage over original drugs.

"Another impetus to develop biosimilars is to ensure that there is enough drug supply in the market. There have been many times over the last year that we have had drug shortages, which can be terrifying," notes Dr. Johnson. She continues, "Imagine trying to treat someone with etoposide [a chemotherapy drug often used in lung cancer treatment] and being told that there's no etoposide… this has already happened in my career! It is not far-fetched to see the same thing happen to biologics. Biosimilar drugs can ensure that we have some redundancy or a backup plan in case there is a shortage of biologic drugs. Having more than one company making such drugs could be a good way to combat supply-chain issues."

Biosimilar drugs do not enjoy universal acceptance in the medical community. Some physicians are concerned about the lack of robust information on the efficacy, safety, and toxicity of these drugs over long periods of time. Such information is important because many of these drugs will be used by patients with chronic conditions. Chronic conditions usually cannot be cured. They must instead be managed with medications over a patient’s lifetime.

Dr. Johnson expresses, "Would I be comfortable substituting a biosimilar for a biologic? It depends upon the context. If we are talking about a biosimilar for adjunctive or supportive care, I will be more comfortable using it. I would be concerned about using a biosimilar as a main monotherapy since that would mean basing the entirety of a patient's care on something that looks mostly like a biologic that worked in the clinical trials… However, this is just my opinion." Adjunctive or supportive medications are those drugs which "support" a patient during their cancer treatment. For example, a supportive drug can be given to increase the blood cell counts of a patient receiving a main chemotherapy drug that depletes the blood.

Dr. DiMarco speaks to the broader provider opinion about biosimilars. "I think provider confidence has grown over the past couple of years,” she says. “Because the biosimilar process was so different from a new drug or generic drug approval, it has taken some time for providers to become aware of and trust biosimilars. The FDA has approved some biosimilars with different indications from the reference in the past which has also caused confusion, ie. bevacizumab biosimilars did not receive approval for ovarian cancer, so it is important to look at the indications. At TJUH, our P&T approved the use of biosimilars for all indications that are approved for the reference product with provider approval, but it’s important to note that oncology biosimilars have not received interchangeable status from the FDA, which is an additional approval process, and allows the use of a biosimilar without physician notification.  The NCCN also states that biosimilars may be used wherever a reference product is indicated."

Will My Insurance Cover Biosimilars?

Wrapped in employer insurance plans, biosimilars can be more expensive

Medical insurance may heavily influence whether you benefit from the lower cost of a biosimilar product. Interestingly, only 14% of insurers preferred biosimilar products. The insurance companies may have contracts with certain manufacturers of reference and biosimilar products, which can heavily dictate which drug a patient can use. This could also mean that if a patient switched insurance providers in the middle of their treatment, they may have to switch their reference and biosimilar product.

"Insurance may require us to use a different product depending on their contracts, so we carry almost all available biosimilars and are very careful when dispensing and compounding due to the similarity between products," notes Dr. DiMarco.

As biosimilar drugs gain traction, insurance policies could change to allow better access to these medications.

Prescribing Biosimilar and Interchangeable Products

Key Takeaways

Biosimilar products are here to stay. More and more pharmaceutical companies are investing resources in manufacturing and developing biosimilars. When considering whether a biosimilar alternative to your current biologic medication may be right for you, you should keep the following in mind:

• Biologics are complex drugs derived from living organisms or their products, such as blood and proteins. Manufacturing them is heavily dependent on the cells used and the conditions used during the process. Many biologics come with a significant price tag.
• Biosimilar drugs are engineered to be similar to the biologics in their therapeutic benefits, safety, and toxicity. Unlike generic drugs, biosimilar drugs are not replicas of their biologic counterparts.
• Almost 40 biosimilar products have been approved by the FDA to date. Many of these are used to treat cancer or chronic medical conditions.
• Biosimilar products may cost less than their biologic counterparts. However, these savings may not necessarily benefit patients as insurance companies dictate which biologic or biosimilar medication they cover. Ironically, an expensive biologic medication may be covered by insurance while a cheaper biosimilar medication may not be. In such a case, a patient would have to shoulder hefty out-of-pocket expenses should they want a biosimilar medication.
• Some physicians are concerned about the long-term efficacy and safety of biosimilar medications. This stems from the fact that these drugs, unlike their branded counterparts, may not have been formally evaluated in human clinical trials. Dr. DiMarco expresses, "There is very little data for switching biosimilars in the same patients since switching data is only required for interchangeability approval, so I would like to see real-world evidence to support this practice."
• If your physician recommends a biologic medication to manage your condition, discuss some biosimilar alternatives thoroughly. Know that the final decision may come down to insurance coverage and out-of-pocket costs.

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