Biosimilars May Change the Treatment Landscape for Inflammatory Diseases

BIOSIMILARS HAVE SIGNIFICANT potential to lower escalating drug spending in the United States, but their adoption into practice in this country has been sluggish; however, this trend may soon change. Merck recently announced the launch of Renflexis (infliximab-abda), the second biosimilar version of the blockbuster drug, Remicade (infliximab). The first Remicade biosimilar, Inflectra (infliximab-dyyb) from Pfizer, launched in late 2016.

During the recent Peer Exchange®, “Clinician and Managed Care Insights on Biosimilars for Inflammatory Diseases” hosted by The Center for Biosimilars™, an expert panel provided an overview of biosimilars, clinician and patient understanding of the biologics landscape, and access considerations with a focus on inflammatory conditions. The panel included moderator Peter L. Salgo, MD, along with experts Allan Gibofsky, MD; Gary R. Lichtenstein, MD; Vibeke Strand, MD; and Cole Wilson, PharmD.

Although biologics account for less than 1% of all prescriptions dispensed in the United States, they represent one-fourth of all US prescription spending, according to Dr. Salgo. The high cost of drugs is an increasing concern, and biosimilars offer hope as a less costly alternative for patients treated with specialty medications. Despite this potential, the adoption of biosimilars has been slow, due in part to knowledge gaps regarding biosimilars among health care professionals, according to the panel.

“I think (biosimilars) have the real potential for lowering costs to the system and possibly increasing resources for patients and increasing their access,” Dr. Gibofsky said. “I think we still need some of that evidence to accrue before we’re fully comfortable, but I do think that the ability to use these drugs more widely will be a significant advantage in the treatment of the chronic inflammatory diseases we’ve been talking about.”

Although different representative organizations have launched programs to increase awareness, such as the American College of Rheumatology’s new Biosimilars Awareness Education Program, education overall is still lacking. Dr. Gibofsky believes the gap lies between the time that the FDA takes regulatory action and when the drug finally becomes available—–which can be at least 6 months, maybe longer. “The knowledge base is building out there, but there are still some misunderstandings that have to be corrected,” he said.

Biosimilars contain living organisms and are designed to be highly similar to the reference product, but not identical. They are manufactured based on knowledge of the primary structure of the reference product—ultimately reverse engineering them. The primary structure, which is the sequencing of amino acids, needs to be the same for a biosimilar and its bio-originator, Dr. Gibofsky said.

“There can be difference in the molecule between a biosimilar and a bio-originator (the reference molecule), but they can’t be clinically meaningful,” Dr. Gibofsky said. “They can’t affect the safety. They can’t affect the efficacy. They can’t affect the purity or the potency of the molecule that we’re dealing with.”

The repurposing of drugs is gaining attention in the research world, in which biologic drugs indicated for a specific disease are being used to treat other diseases. Within the framework of biosimilar development, the FDA has allowed interchangeability for specific areas initially approved for the originator product.

“I think one of the concerns is that the FDA has made it very clear that the label for a biosimilar is identical to the label for the reference product,” Dr. Strand said. “That’s going to make it very hard for people to try to figure out how to report pharmacovigilance.” For biosimilars, 28 states currently allow interchangeability. According to Dr. Wilson, the standard for generic products that have been on the market is not the same standard for biosimilars.

Biosimilars are designed with a goal to decrease drug costs and ultimately increase patient access. This decrease in cost is associated with how well the manufacturer of the biosimilar can negotiate compared with the negotiation skills of the manufacturer of the reference product.

“You can anticipate that you’re not going to see the bio-originator manufacturer stand still while someone else comes in and tries to eat their lunch,” Dr. Gibofsky said. “So, I’m not surprised to hear that there may be systems in which the bio-originator is priced even lower than the biosimilar, which was promised to be the reduced price.”

It is difficult to determine which drug will be cheaper, and by how much, due to the role pharmacy benefit managers play in making the decisions and the discount portfolios, according to the panelists. With the portfolios, there may be discounts for uses of various products—and there is no way of knowing what those discounts are.

Dr. Gibofsky spoke about his personal comfort level of biosimilar use by dividing patients into 3 categories: new starts, stable, and sleeping baby. For new-start patients, it is difficult to argue against putting them on a biosimilar. For patients who are stable and achieved that state relatively easily, it would not be that difficult to switch them to a biosimilar. But challenges arise in patients who have struggled to get to the point of low disease activity and remission. This type of patient is referred to as a “sleeping baby” because you don’t want anything done to disturb them. It would be difficult to switch the patient, and they would have more difficulty accepting the switch to a biosimilar, according to Dr. Gibofsky.

Two European switch clinical trials funded by the Norwegian and Danish governments examined the effects of switching from a bio-originator drug to its biosimilar. The results showed noninferiority when comparing the 2 products, according to the panel. Although there is promise when switching products to formulary or considering the use of biosimilars, the question remains whether the European studies are translatable to the United States and how this will that affect formularies, Dr. Salgo noted.

As far as costs in the rheumatology space, biosimilars typically start off slightly less expensive, but their threat is causing a cost reduction across the market. The current challenges with insurance companies and bio-originators will largely be the same with biosimilars. Dr. Gibofsky believes the prior authorization requirements and hurdles will be the same for biosimilars. “I think we are going to see insurance companies selecting favorite agents based on factors unrelated to their clinical applicability,” he said.

For rheumatologists, prior authorizations are one of the biggest expenses in terms of time and money. Many brand biologics cost hundreds of thousands of dollars, even with discounts, which causes financial toxicity that can be just as harmful as any adverse event, according to Dr. Wilson.

From the perspective of the federal government, opening access may be less expensive per patient, but the more patients who come in, the higher the total bill gets—in other words, an aggregate bill. To reduce the financial burden of biologics, manufacturers offer discount programs, such as co-pay assistance; however, these services have yet to be put in place for biosimilars. It is also important to consider that there is little assistance available for generic-type products, which means biosimilars could follow the same trend.

When deciding which drug to prescribe, health care providers typically review efficacy, safety, adherence, tolerability, and cost, in addition to individual patient characteristics, according to Dr. Gibofsky. The interesting thing about biosimilars is that although they cannot compete with the reference product in the way physicians traditionally review drugs, they can offer a lower cost for the same clinical outcomes.

While cost may be a major reason that physicians choose to prescribe a biosimilar, some may be concerned that switching patients from a reference product may not achieve the same disease control, despite data suggesting otherwise. Physicians may also be hesitant to prescribe biosimilars if the reduced price does not necessarily translate into patient savings. In some cases, a patient’s co-pay may be the same, with savings only being seen by the health care system, according to the panel.

Biosimilars typically offer a cost reduction ranging from 15% to 30% of the cost of the reference product compared with an approximately 85% reduction from standard generic drugs. As such, the cost concessions from biosimilars may not be enough to change the prescribing habits of physicians, according to the panel. Dr. Strand said that contracting will play a significant role in how much biosimilars will be discounted.

The manufacturing and approval processes are costly for biologic drugs, which may be another reason why the initial discounts for biosimilars are not more remarkable.

The panel also noted that the reference product has already generated revenue, causing manufacturers to have the financial ability to provide larger discounts. Therefore, it may not be a question of why biosimilars are less costly, but why reference products are not discounted more, according to the panel.

In Europe, a majority of biosimilars offer a 30% discount, which is at the higher end of what is expected in the United States. Dr. Gibofsky said that these countries are largely single-payer systems, which opens the door to price negotiations due to the expansive size of the contracts, as opposed to the health care system United States. Additionally, since biosimilars were introduced in Europe so long ago, physicians tend to be more comfortable prescribing the drugs, which may lead to higher manufacturer discounts.

Ensuring that a biosimilar is covered by payers is crucial because it likely will not be prescribed without reimbursement. Taking cost out of the conversation, payers must consider numerous factors, including clinical efficacy, appropriateness, and comparisons to the reference product. While the goal is to secure access for patients, limited networks may provide a challenge for continual care. For example, Dr. Wilson said that patients may have access to the drug through an acute setting, but could lose coverage when transitioned to an outpatient setting. These are considerations payers must account for to ensure that they are being fiscally responsible and are lowering health care costs.

This issue may be further complicated by state-by-state approvals of biosimilars. Even if the FDA approves a biosimilar as interchangeable, many states have passed legislation that dictates whether the reference product can be substituted for the biosimilar without involvement from the prescriber. However, Dr. Lichtenstein believes that it might be more appropriate for the federal government to make a country-wide regulation regarding interchangeability. In some cases, state legislators may not have all of the necessary information to make the decisions, whereas federal legislators have access to nonpublic information and clinical trials.

Both physicians and patients are entering a new world with the introduction of biosimilars. For newly diagnosed patients, physicians can embark on the standard discussion about treatment and initially prescribe a biosimilar, but switching patients off a reference product may be more challenging. Patients who are not responding well to a biologic drug, however, may be more willing to switch to a biosimilar. Patients may also be less likely to switch treatments if they have the same co-pay.

Prescribers also are tasked with educating patients and reassuring them that they will achieve the same results on a biosimilar as they did on a biologic. The experts suggest that if patients are concerned over the small changes in biosimilars, prescribers should assure them that the drugs have been tested in different disease states and data suggest the change will not be harmful. Dr. Strand noted that more high-level details about biosimilars are known compared with the reference product. The panel emphasized that physicians need education regarding biosimilars to become more comfortable with prescribing the drugs, which may result in larger uptake.

Since there are more than 50 biosimilars under review by the FDA, it is clear this new class of drugs is here to stay, according to the panel. This requires physicians to plan their course of action when talking to patients about treatment. Manufacturers have to do a great deal of planning, from creation of the biosimilar to its approval. They also must conduct extensive studies to determine how switching treatments will affect patients. Although the biosimilar industry is developing slowly, the experts agreed that the drugs will likely change the way diseases are managed for numerous conditions.

Dr. Wilson concluded that when generic drugs emerged, conversations took place that were similar to the current issues surrounding biosimilars, which he said may turn out to be as important to the industry as generics.

“The opportunities with biosimilars are great. They’re great for patient choice, they’re great for provider choice, and they can have a lot of cost savings and opportunities,” Dr. Wilson said. “I think the future will tell a lot of the litigations and the limitations. The access channels of some of these (that first come to market) will really pave the way for the future of biosimilars and how we use them in our practice.”