Written by Omar L. Gallaga

Complex, biologically derived drugs meant to cost less face skepticism and growing interest.

To understand why there has been so much interest and questioning in the medical industry on the subject of biosimilars in recent years, one needs only to look at the fight against multiple sclerosis. In the 1990s, after the first generation of disease-modifying therapies emerged, the costs of treating the disease began to skyrocket, from around $8,000 to $11,000 per year at the time to $80,000 per year today.

Biosimilars — which are designed to accomplish the same therapeutic goal as a drug that uses living organisms, but at a much lower cost — have been pursued globally as a way of keeping MS treatment costs down.

Victor Rivera

Victor M. Rivera, M.D., distinguished emeritus professor of neurology at Baylor College of Medicine, wrote about the cases for and against biosimilars in a published study about MS biosimilars, concluding that it’s still too early to determine if they are the answer.

Unlike generic medications, which are molecular-level copies of existing drugs, biosimilars face a much harder road toward approval and acceptance, said Dr. Rivera.

“The story for biosimilars is totally different. There are very large and complex molecules used to treat rheumatological conditions, autoimmune disorders, cancer, and multiple sclerosis, among others. They cannot be precisely copied or reproduced,” said Dr. Rivera.

A lack of head-to-head medical trials or Phase III studies, he says, could cost more than $100 million. “For that reason, biosimilars have not provided efficacy and safety data,” Rivera says.

But the potential for cost savings has kept the pursuit of biosimilars going. One estimate from the Federal Trade Commission suggests that biosimilars could save the U.S. health care system around $250 billion by 2022.

The Food and Drug Administration began gradually approving them in 2015, starting with Zarxio, which is similar to the bone-marrow stimulant Neupogen used for cancer patients. As of this writing, the FDA has approved 26 biosimilars. According to the FDA, approved biosimilars must have no clinically meaningful differences from their reference product in safety, purity and potency. Biosimilars are in development by major drug companies, including Pfizer and Novartis.

The FDA says that its “abbreviated approval pathway” was a response to rising drug costs and the growth of biological treatments. “Biological products are the fastest-growing class of therapeutic products in the United States and account for a substantial and increasing portion of health care costs,” the FDA says on its website. “Congress, through the Biological Price Competition and Innovation Act, created an abbreviated approval pathway to provide the public with greater access to safe and effective biological products. The pathway provides more treatment options, potentially lowering health care costs through competition and increasing access to lifesaving medications.”

Questions Before Usage

Some Texas doctors say that the FDA’s approvals, which have progressed more slowly than in other parts of the world, are only the beginning in determining whether biosimilars can be used in treating patients.

Bincy Abraham

Bincy Abraham, M.D., a gastroenterologist and director of the inflammatory bowel disease program at Houston Methodist Hospital, said, “Even when the FDA approves a biosimilar, it isn’t necessarily available for us to use. Insurance has to approve it for our patients as well,” she said.

Complicating matters, she said, is that a biosimilar and its reference medication can’t be swapped back and forth during a course of treatment, as with generics. Dr. Abraham also stated that state laws can impact whether a patient can refuse an interchangeable biosimilar paid for with government agency funding.

Texas is one of 45 states, plus Puerto Rico, that allows or requires pharmacists to dispense interchangeable biosimilars.

“It’s a hot topic because even though biosimilars were approved a few years ago, it’s now finally taking on momentum in the United States where it may reduce costs to the patient’s insurance, infusion centers or pharmacies,” said Dr. Abraham.

But, she said, “We cannot consider biosimilars in the same way that generics are treated due to the complexity of their molecular structure, how they are produced, and the type of data needed to show similarity in effectiveness and safety.”

She said that for FDA approvals, drug companies only have to show that a biosimilar is an effective treatment for one condition or disease state, not for every way in which the reference drug might be used. “Many physicians have been hesitant to use it,” Dr. Abraham said, “mainly due to lack of experience, prior lack of data, and acceptance from the FDA to allow for extrapolation of data. More recent studies, and clinical trials to evaluate the biosimilar in each indication it is approved for can alleviate our concerns.”

Sheila Ryan

That’s a concern shared by Sheila Ryan, J.D., director of clinical research operations at Memorial Hermann-Texas Medical Center. She said that while biosimilars go through an analytical review, animal studies, assessments of toxicity and clinical trials to establish comparable efficacy, there’s still more work to do.

“Further post-market studies are required to independently establish the safety and effectiveness of the biosimilar as well as to generate real-world data in patient populations,” said Ryan. “Researchers are interested in learning more about the safety profile of biosimilars and whether ‘high similarity’ can translate to ‘similar clinical results.’”

Cost Complications

But the measured skepticism doesn’t mean that groups such as Memorial Hermann’s Pharmacy & Therapeutics Committee aren’t interested in hearing more. Ryan says that biosimilars could benefit oncology, gastroenterology, hepatology and diabetes treatment by offering cost-effective alternatives to current treatments and helping reduce overall expenses on prescription drug prices.

So far, though, those savings haven’t materialized, she said, most likely due to the complexity of manufacturing, the preferences of payers and pharmacy benefit managers, and post-approval research costs.

Dr. Abraham agrees, suggesting that there are more factors at play than just getting the cost of biosimilars down below the cost of the originator medication.

“It might come down to how rebates take place between insurance companies and the company that creates the product,” said Dr. Abraham, “It’s not very straightforward.” A hospital or infusion center, she says, may decide to save costs with a biosimilar, but if a patient’s insurance only approves an originator drug, the hospital may have to go through an appeal process to use the biosimilar. “They may get the biosimilar, but when they get discharged, they have to go back to the original,” she says. “They’re switching back and forth, which is not what the FDA approved, but it’s what happens in real life.”

Dr. Rivera said that some regions of the world that have been fighting higher rates of MS in their populations have been relying on research data from originator medications instead of new data to get the medications on the market. For the medical industry to see real savings from biosimilars that would benefit insurance companies and individuals, they’d have to be at least 30% less expensive, he explained.

Though a few dozen biosimilars have made it to the market, that doesn’t mean the journey is over and that challenges don’t persist, even for the FDA approved treatments.

In addition to being more expensive to develop than generics, biosimilars will need to continue to prove safe even though they are far more complex, Ryan says.

“Even minor changes in the development of the product can affect their safety and/or effectiveness,” she says, “Additionally, because they are derived from living cells, they may be susceptible to even small changes in the environment.”

Most importantly, Ryan added, biosimilars are unique from chemically derived drugs because they have the potential to stimulate an immune response in a patient’s body is seen as a foreign substance. “For those reasons, it is critical to establish post-market monitoring and additional clinical trials for all available biosimilars.”

What are biosimilars?

Biosimilars are drugs modeled after existing medications that use living organisms as ingredients. They are meant to lower costs by providing an alternative treatment to an originator medication.

How are they different from generics?

Generics are exact molecular copies of drugs. Because they are derived from living organisms, biosimilars are larger, more complex kinds of treatments that are considered “highly similar” to the originator drug. They are expected to accomplish the same therapeutic goals.

Are they FDA approved?

Twenty-six biosimilars have been approved since 2015 by the FDA in an abbreviated approval process that does not require head-to-head clinical trials or separate trials for every application of the biosimilar.

What areas of medicine are most likely to benefit from biosimilars?

Post-cancer treatments, immune system disorders and inflammatory diseases are some of the areas in which biosimilars could be used.

Can biosimilars work better than originator drugs?

No, they are meant only to be as effective as the drug they are based on, not to provide additional benefits. Their appeal is primarily that they could be less expensive than an expensive existing treatment.