By Fran Gregory, PharmD, MBA, vice president of emerging therapies
It’s no exaggeration to say that biosimilars have the potential to reshape the future of U.S. healthcare. That’s why I find my role at Cardinal Health so rewarding: I lead a team that works with stakeholders across the healthcare continuum as they navigate the evolving biosimilars landscape. We work with manufacturers to gain regulatory approval, distribute biosimilars to providers and pharmacies, and gather and share insights about biosimilars.
Here, I provide a brief overview of biosimilars and update on biosimilars for Humira® (adalmumab), which could dramatically increase access; outline some challenges to widespread adoption; and highlight some of the work my team and I are doing to address those challenges.
Biosimilars are medications that are highly similar to U.S. Food and Drug Administration (FDA)-approved reference biologics – the fastest-growing class of drugs in the U.S., bringing innovative, life-changing treatments to patients with cancer and chronic diseases. Biologics are made from living organisms like animal cells, bacteria and yeast. Because they’re expensive to make, may require temperature-sensitive storage and are typically administered via injection or infusion, biologics are among the most expensive pharmaceutical treatments available. In fact, biologics account for nearly 40% of U.S. drug spending, despite comprising less than 3% of prescriptions, according to the nonprofit Biosimilars Forum.
However, because biosimilars provide the same treatment benefits as their original biologics – called reference products – they are bringing more competition to the market, helping to lower costs and increase patient access to treatment.
Thanks to new biosimilars for Humira, the world’s top-selling biologic drug with annual sales topping $20 billion, we are anticipating a significant change in the biosimilars market. Humira is an injectable immunosuppressive drug used to treat several autoimmune conditions, including rheumatoid arthritis, Crohn's disease and ulcerative colitis. The first adalimumab biosimilar entered the market in January, and several others have launched since. It is expected that over 10 Humira biosimilar variations will be on the market by the end of 2023.
A pharmaceutical industry milestone for biosimilars
Groups representing insurers, patients and employers are eager for biosimilars to usher in more competition to Humira and the potential for savings is huge. Of the $38.4 billion in projected healthcare savings during 2021-2025 due to new biosimilar competition, more than half are expected to come from Humira biosimilars entering the market in 2023. How quickly these projected savings are realized depends on multiple factors, including pharmacy benefit manager and payer pricing tactics, formulary coverage criteria, biosimilar product pricing and, significantly, providers’ willingness to prescribe these therapies.
Changing provider perceptions
The willingness of providers to prescribe biosimilars may vary by specialty and by condition, according to the Cardinal Health 2023 Biosimilars Report. Humira is clinically important to gastroenterologists, dermatologists and rheumatologists, so these specialists must be familiar with and willing to prescribe the new biosimilars. Among rheumatologists surveyed for the report, 76% stated that they are very familiar with biosimilars, but only 62% said that they would be very comfortable with prescribing a biosimilar. Though there is strong evidence that the availability of biosimilars will have a positive impact on patients, only 54% of rheumatologists agreed or strongly agreed that biosimilars would positively impact care.
Among gastroenterologists, 93% of the physicians surveyed indicated they are at least somewhat comfortable prescribing a Humira biosimilar once it becomes available. Among dermatologists surveyed by Cardinal Health, 48% were concerned about the efficacy of biosimilars, and nearly 50% said the economics of biosimilars are not favorable enough to switch.
At Cardinal Health, we are committed to changing these perceptions. By providing education to prescribers, partnering with payers to optimize acceptance, working to educate broadly through webinars and continuing education for healthcare professionals, and engaging in initiatives to keep the provider community aware of the pipeline, we continue to make progress in biosimilar awareness and confidence.
The importance of interchangeability
Like generic drugs, biosimilars are expected to produce the same clinical result as a reference product at lower cost. However, unlike generics, which are the same as their brand-name products, biosimilars must match their reference product by strict FDA criteria and evidence. This is an important distinction: A pharmacist can substitute a generic for a brand-name product prescribed by a provider but can NOT substitute a biosimilar for its biologic reference product unless that biosimilar has been given an “interchangeability” designation from the FDA. Very few biosimilars have yet to earn this designation.
Obtaining an interchangeability designation requires that biosimilar manufacturers make additional investments in their data set submitted to the FDA. This additional step includes testing to prove that switching back and forth between an interchangeable biosimilar and the reference product has no additional risk or reduced effectiveness. This testing is time-consuming, costly and many manufacturers choose not to pursue it. In addition, any additional costs incurred by the manufacturer will ultimately contribute to the cost of the biosimilar.
While one of Humira's biosimilar competitors — Cyltezo® — has gotten an FDA designation for interchangeability that allows for automatic switching, others have not.
In prescribing a biosimilar, a provider must designate which biosimilar they would like dispensed. When there is more than one biosimilar for a single reference product, it’s particularly challenging, because the provider may not know which biosimilar is preferred by the payer or PBM covering the patient. The provider may not recall all the individual names of each biosimilar. Then, when the prescription reaches the dispensing pharmacist, that pharmacist can’t substitute a biosimilar for an original reference biologic competitor without the provider’s instructions.
Whether due to the additional administrative hurdle or concerns about safety or efficacy, over 60% of providers we surveyed said they would only feel comfortable prescribing Humira (adalimumab) biosimilars that have interchangeability designations.
There have been many studies to evaluate the safety of switching to a biosimilar from a reference biologic. To date, none have found differences in safety, efficacy or the likelihood a drug will trigger an unwanted immune response. The same holds true for studies focused specifically on Humira and its alternatives. In fact, Frontiers in Pharmacology published a 2022 review of 21 studies involving nearly 3,000 patients that found no difference in safety or effectiveness when switching from Humira to eight different biosimilars.
Cardinal Health will continue to help educate providers by sharing peer-reviewed literature supporting the safety, efficacy and cost-effectiveness of biosimilars.
Impact of product attributes on interchangeability and adoption
Further complicating the process to gaining an interchangeability designation, biologics can be manufactured with different attributes. For example, biologics can have different concentrations, meaning a difference in strength or potency of the biologic. Some biologics may also have additives that increase the shelf life of the product or make it easier to deliver to patients. The delivery of a biologic may differ as well. Some biologics can be delivered with injectable pens, while others require delivery with a syringe. Different product attributes are designed to make it easier to get treatment to patients in the most effective way possible. For example, a biologic with additives and a longer shelf life could improve patient access and availability as that treatment is viable for a longer amount of time.
Humira is available with both a high-concentration and a low-concentration formulation. Likewise, many Humira biosimilars will be available with a high- and/or a low-concentration formulation. (More than 85% of current Humira patients are treated with high-concentration formulation.)
Another variation in Humira reference products is the presence or absence of citrate, a buffer that keeps the medicine stable. It is commonly found in many injectable medications, but it may cause a burning sensation at the injection site for some patients. Citrate-free Humira contains a different buffer that doesn’t cause the same burning and pain commonly reported by patients.
More than 80% of Humira patients now utilize the citrate-free version. Biosimilar manufacturers paid close attention, with most seeking approval for a citrate-free formulation of their Humira alternatives from the outset. The majority of FDA-approved Humira biosimilars are citrate-free. This is one less barrier to adoption.
Finally, more than 90% of Humira patients utilize an auto-injector pen which provides an easier injection method than prefilled syringes. Not all currently approved Humira biosimilars offer an auto-injection device. Patient ease and preference matter, and it is possible that patients will only switch to alternatives that offer a delivery method they are comfortable and familiar with.
Biosimilar manufacturers are continuously working to best match the reference products characteristics, and even develop better options for patients where that is possible and permitted by FDA regulators. These efforts will continue to help payors, providers and patients as they evaluate the options that biosimilars will bring.
The future impact of biosimilars
Ultimately, as their adoption increases, biosimilars have the potential to increase patient access to what is currently considered the best standard of care for many chronic, complex and life-threatening conditions. Biosimilars offer providers additional options and reduce U.S. healthcare costs by mitigating prescription drug spending. However, fully realizing these benefits will require stakeholders throughout the healthcare ecosystem to recognize and work to remove barriers to adoption. The recent wave of Humira biosimilars presents an opportunity to create effective adoption strategies that help patients to achieve better outcomes at lower cost.
These are exciting times in the biosimilars space. As more biosimilars become available for even more life-threatening conditions, it’s easy to see a world where there will be more access to these medications at more affordable prices. When I think of the work that Cardinal Health is doing in this space, I only see positive change and growth as we continue to collaborate and accelerate the adoption of biosimilars and help improve the lives of patients.
Fran Gregory is vice president of emerging therapies at Cardinal Health, where she leads the teams that help biopharma pioneers bring cell & gene therapies and biosimilars to the patients who need them. She has vast experience innovating in healthcare, with a continued focus on high-cost and high-impact complex therapies. She has a passion for navigating through complexity to optimize medication outcomes for patients and for creating cost-effective solutions for the healthcare system.