One of the most effective methods of controlling drug costs has long been the substitution of generic drugs in the place of more expensive brands. For the vast majority of medicines, where generics and brand-name offerings can be said to be medically identical to one another, such a substitution can be made without worry. Biologics, however, are raising important questions about what it means exactly for two drugs to be interchangeable.

“Decisions about medication are personal and should be between a patient and their health care providers only.”

A lot of drugs on the market are what are known as small-molecule drugs, meaning that they are comparatively simple in chemical structure and can be synthesized identically under laboratory conditions. A small-molecule drug created in one lab is identical on an atomic scale with one created in another lab.

Biologics, on the other hand, are much more complex molecules (in fact, they are proteins) created through biological processes in living cells. The exact chemical structure of the drug is dependent on many manufacturing processes and factors, as well as on the idiosyncrasies of the specific type of cell used to produce them. A manufacturer is not able to reproduce a molecularly identical copy of another company’s biologic in their own laboratories since they are not privy to the exact conditions under which the original molecule was made.

Not generics, but subsequent entry biologics

It is possible, however, for labs to work backwards from the structure of the biologic and develop their own process to create a drug that is substantially similar, and then have that new drug approved as an alternative. These subsequent entry biologics (SEBs) are also known as biosimilars. “Biosimilars are effectively reverse engineered,” explains Joanne Simons, Chief Mission Officer at The Arthritis Society. “It will never be identical. It will be similar, but not the same. Think about two different types of apples. They’re both apples, but one may be a McIntosh while the other is a Granny Smith.”

The question of what exactly a biosimilar is and how it relates to the originator (or innovator) biologic is of particular importance right now to rheumatologists and arthritis patients, because the first two biosimilars that were approved for use in Canada are both treatments for inflammatory arthritis. In the coming years though, we can expect to see many more biosimilars entering the market, and the issues rheumatologists are wrestling with now will become relevant across a wide spectrum of diseases and conditions.

So what do I need to know?

Perhaps the most important thing to understand about biosimilars is that they do go through a rigorous evaluation approval process to show that they are as safe and effective as the original biologic at treating the diseases they are indicated for. “To be approved as a biosimilar, they have to show that the drug has similar efficacy,” says Dr. Michel Zummer, Chief of Rheumatology at Hôpital Maisonneuve-Rosemont in Montreal. “It’s not an identical drug as far as structure is concerned, but because of the approval process, the efficacy and the safety have to be similar.”

Being similarly effective is not the same as being interchangeable. “We don’t know enough about inflammatory arthritis to predict who is going to respond well to which drug or which molecule,” says Dawn Richards, VP of the Canadian Arthritis Patient Alliance. “By switching medications, there is a possibility of causing a change in a person’s condition. If someone is stable on their medication, I don’t think any rheumatologist would suggest changing that person’s medication.”

Dr. Zummer echoes that same sentiment. “Usually, with a generic drug, you can switch back and forth regardless of the manufacturer and it’s no problem,” he says. “But with biologics and biosimilars, we don’t know what the impact of switching is going to be, so there are potential concerns. The data is still forthcoming.”

Concerns over payers treating biosimilars as generics

The biggest concern is that health insurance payers, whether public or private, might seek to switch stable  patients from one drug to the other in order to realize cost savings, despite voices in the medical community expressing concerns about the risks of doing so. This is where the precedent of generic drugs becomes a problem. While the chemical difference between a biologic and its corresponding biosimilar is minimal, it becomes very easy to make the mistake of assuming they are identical.

To help combat this, many are arguing that it is important to ensure that biosimilars are named and labelled in such a way as to make their similar-but-different status clear. “They are not identical molecules,” says Richards. “So, like any other drug out there, they should have their own name.”

Greater choice should lead to informed decisions

It should be emphasized that the concern primarily surrounds the idea of patients being mandated by their insurers to switch from one drug to another for cost reasons against their own wishes and without the advice of their doctors. In other situations, the case for using the biosimilar can be as strong or stronger than that for using the originator biologic. “If you have not yet been on a biologic, it may be perfectly reasonable that you first try the biosimilar,” says Simons. “In the case where your current biologic has stopped working, again, moving to the biosimilar could be a great option.”

When treated as the similar but distinct drugs that they are, biosimilars are unquestionably a positive development for patients. “These are additional options for patients to have,” says Richards. “It’s just a matter of being given the choice to make the switch or at a point where it makes sense in their disease journey, rather than having that imposed on them. Decisions about medication are personal and should be between a patient and their health care providers only.”

It is imperative that Canada, the provinces and the private health care industry take this opportunity to have a long look at biosimilars in order to create policies and practices that take into consideration the unique characteristics of this new class of drugs. Doing so will be vital to preserving access for Canadians to the treatments they and their doctors agree are best.