Rheum360: Focus on Biosimilars

Biosimilars Q and A

Leonard H. Calabrese, DO

What was the stimulus for biosimilars to become available in the United States?

Biologic agents have been available in the United States for more than 2 decades. The patent length on biologics exceeds that of nonbiologic therapeutics. However, the end of patent exclusivity is now a reality for several of the early-introduced agents, including infliximab, adalimumab, and rituximab. With the prospects of these expensive drugs going off patent, there was great interest in developing agents, which we now refer to as biosimilars, to compete in the marketplace at reduced prices.

The affordability health care legislation passed under the Obama Administration explicitly carved out a pathway for the approval of biosimilars. This process is based on an inverted pyramid of research that emphasizes demonstrating a high degree of similarity in the pharmacokinetics, pharmacodynamics, immune effects and immunogenicity, as well as other characteristics of the biosimilars, creating a portfolio of evidence that leads to US Food and Drug Administration approval.

The clinical development programs for traditional biologic agents are long, complex, and extremely expensive. The development of biosimilars has been shortened. Biosimilars can be approved with relatively small pivotal trials in a single disease. Then, by extrapolation, these data and other supporting evidence provided by the biosimilar manufacturer can be used as the approval basis for all the other indications for the specific originator biologic.

The greatest impetus for the development of biosimilars has been financial. These drugs, which are now approved throughout the world, have led to tremendous cost savings, particularly in countries with single-payer systems that can leverage their buying power to out-compete the originator drugs. In the United States marketplace, these cost savings have not yet reached the dramatic levels seen abroad. However, with increasing numbers of biosimilars, there is hope that progressive cost savings will be experienced.

How do you think the reception has been for biosimilars from both a patient and provider standpoint?

A tremendous effort was undertaken to educate patients and providers about the scientific basis of biosimilars. Patient advocacy groups have asked for explicit information regarding their efficacy and safety, and numerous forums and organizations have been created to disseminate this information. Providers have also been exposed to a variety of educational initiatives at the local, regional, and national levels. My experience in this area suggests that most providers are comfortable with the efficacy and safety of biosimilars—at least when they are used initially—and not as substitutions for existing originator biologics.

At the same time, much of the decision-making regarding the use of biosimilars is not under the control of either the patient or the provider. It is more under the control of third party payers as well as hospital and health care system pharmacy and therapeutics (P&T) committees.

What are some of the barriers that physicians face in obtaining biosimilars for their patients and how can they be overcome?

For most physicians, who typically are not in solo practice, decisions around the use of biosimilars are out of their individual control. In large health care institutions, P&T committees decide which agents to use and how they will be administered.

Many patients have asked whether biosimilars would be appropriate for them and whether they would save money by switching to or initiating a biosimilar agent. Unfortunately, providers cannot answer these questions readily because each third-party payer has different policies and price structures. Currently, intense negotiation is ongoing among health care systems that buy biologic agents in bulk and the companies that make the originator biologic, as well as companies that make biosimilars of those agents. Time will tell what final price structure will evolve. Unfortunately, currently in the United States, the cost savings have been only a fraction of that reported in foreign countries with single-party payer health care systems.

How do you see biosimilars altering the field of rheumatology in the near future?

In my large group practice setting, we have not felt the impact of biosimilars at all. Our institution has not adopted a biosimilar that affects the practice of rheumatology; thus, I have been buffered from this. In talking with my colleagues, the landscape differs from institution to institution and from city to city. I am hopeful that multiple biosimilars arriving in the marketplace will drive down cost and give patients and providers more options. I personally am comfortable with the science of biosimilars and do not see current evidence suggesting that a risk is associated with their use.

A final point is that of pharmacy-based substitution. One potential drawback of biosimilar use is the removal of control over whether a patient is given an originator compound or a biosimilar coming from a third party, such as a pharmacist or third-party payer system. Theoretically, a pharmacist could substitute 1 or more biosimilars without the physician’s approval. Legislation has passed and is pending in numerous states that would prohibit this interchangeability, which I believe is a useful and important regulation that needs to be formalized.

Are there any investigations of biosimilars you believe will have an impact on the rheumatology field?

Currently, there are biosimilars for many of the biologics that were among the first to be approved nearly 20 years ago. I think that having several versions of a biosimilar for a given originator biologic will greatly enhance the competition in this space and drive down costs. There is nothing in terms of scientific or technical obstacles that cannot be overcome to produce a biosimilar of virtually any biologic agent. The greatest protection that large biotech pharmaceutical companies have is in the courtroom, with robust patent protection.

Finally, I do not expect a major frame shift in biologics and practice patterns until patents expire for the new small-molecule agents, such as the kinase inhibitors that have been approved to treat rheumatoid arthritis, psoriatic arthritis, and other diseases. Although, by definition, new products based on these targeted synthetic agents will not really be biosimilars—they will offer the potential for a truly low-cost competitive drug in the same space where we are now using originator biologic therapeutics. However, that prospect is still many years away.