Generics, Biosimilar, Interchangeable OH MY!

Generics, biosimilar, interchangeable OH MY!

With the introduction to lower-cost insulin options on the market, the message on what we’re actually using is unclear. 

One of the most common questions that diabetes clinicians get is “My insurance changed its preferred brand from X to Y, should I make the change? What’s the difference?” With more manufacturers getting in on the insulin production game, and even long-time players producing cheaper insulin products, the market is becoming more diverse, so let’s take a moment to look at the different terminology in use and what it means for us as insulin users specifically.

What Does Generic Mean?

Most of us are familiar with the pharmaceutical industry terminology of brand and generic. A generic name is the scientific name given to a specific chemical compound. These names are assigned by the US adopted names council and the World Health Organization so that a single chemical compound is known by the same name around the globe. (In the diabetes world let’s take glimepride for example) This name often tells us something about the drug in use, for example the ending ide is common to sulfonylurea medications. You’ve probably seen -sone on the end of a lot of steroidal medications or -olol on beta blockers for hypertension. Not all generic drug names follow these kinds of naming rules, but the generic names help healthcare systems and chemists keep chemical compounds straight.

When a pharmaceutical company initially creates a new compound they submit for a drug patent. Patents give that company exclusive rights to produce and sell that chemical compound for a specific amount of time. This is the time they have the opportunity to maximize profits. At this point they will “Brand” the medication. They give it a catchy, memorable or stand out name. (So our chemical compound glimepride becomes brand name Amaryl) This name has nothing to do with what the medication does. In fact the company can change the brand name along the way (6 years ago a medication used to treat depression changed its brand name because it sounded similar to another medication that had a massive safety issue. The company wanted to avoid bad PR for their drug).

Since the drug patent is on the very specific chemical make up of a single drug companies jockey for position. The tweak the molecule and chemical make up of compounds trying to get the best result or the lowest side effect profile or even just similar results with a compound just different enough to let them get their own patent for that drug. Therefore we end up with lots of pharma companies with essentially the same drug with slightly different generic names but very different brand names.

Generic medications must prove that their production and product is 100% the same as the established drug profile. So brand name glimepride must be the same whether it is called glimepride or Amaryl on the label. In most states, and for most medications a pharmacist can substitute a generic for a brand drug without physician approval. The physician must indicate on the prescription order that they brand written must be used and can not be substituted for generic to guarantee the specific brand.

Now let’s shift form compounds to biologics. Biologic is a specific name given to pharmaceuticals that are derived from living organisms rather than chemical compounds. These are typically proteins, hormones, vaccines etc. Insulin is a biologic medication. Because the drug patent is not only given to the product but the organism from which it is derived, we can not make absolutely 100% identical versions of biologics. (The organic process is simply too expansive to be exactly replicated all of the time) by definition we can’t have “generic”  biologics.

So the FDA uses the term “biosimilar” biosimilar drugs must proven to have:

• the same clinical effects on the body
• be given by the same route (oral, injection etc)
• be the same potency at the same dosage
• have the same side effect profile

These biosimilar drugs cannot be substituted without doctor approval. However, this does not stop insurance companies form contracting these for preferred brands or even on the “generic” tier of coverage. (This is why the media often uses the language “Generic insulin” though strictly speaking there is no truly generic insulin, just those covered at the same tier as generic drugs on insurance formularies) This is an enormous cost-benefit for people with diabetes, but we are often left feeling victimized. We had no choice in this medication change, and this rattles our trust. Does this medication really work like what I’ve been using? Will this disrupt my management?

In a recent meta analysis of over 6000 patients using biosimilar insulin products there was found to be no statistical difference in efficacy, immunogenicity (immune response to the insulin), or safety. This was true across all types of diabetes, durations of time with diabetes as well as durations of insulin action. This is an importance piece because timing of insulin is important. Because generic and interchangeable medications have proven equal efficacy, dosage, etc we should expect to be able to switch to interchangeable insulins with no change in dosage. This has been an important piece to consider in making a medication switch between insulins. We advise trying an interchangeable and simply remain aware of differences in timing or response to different buffering agents or suspensions. These differences would be quite rare, but possible.

There is a higher tier of biosimilar approval called biologic interchangeable. These medications must meet all the approvals of a biosimilar medication with the additional proof of:

• Safety and efficacy of switching between “brand” and interchangeable medication.
• Only non-active elements of structure may differ (such as suspension or buffers)
• Must show no difference in clinical impact from “brand”

If a medication can prove all of these then it can be approved for a substitution by the pharmacist without prescriber as a generic would.

Last year we saw the FDA approval of the first Interchangeable insulin, Semgee (Insulin glargine yfgn) which can be swapped with Lantus (Insulin glargine). 

When we live life with diabetes new medications are going to come along. We will always be trying new things, and sometimes it is because we want to, and sometimes it is because we are pressured to by insurances or finances. We should balance the worth of the fight for our rights and preferences with the benefit to our clinical and mental wellness. The bottom line is we don’t know if it will work for us until we try it. It may have no impact at all but save a lot of money and a ton of time. It may even be better, and we’d never have known if the change had not been thrust upon us. And if it does have a negative impact, we remain vigilant, and then fight for what is best for us at that time. We can work with our prescribers to get what is called an “appeal by failure”. If insurance wants us to change to a generic or biosimilar/interchangeable medication, we can try it and if it shows that it has a negative clinical impact or unwanted side effects our doctors can record that and send that information to insurance companies to get the original agent approved.  Communicating with our prescribers and remaining open to change are important skills in diabetes management.  I also remind patients to be aware of our own biases. If we go into a switch to a biosimilar or interchangeable medication feeling negatively (We often are angry about being dominated by our insurance companies, or blindsided with an unexpected change in medication) we will tend to go in with a negative bias toward the medication. With this bias every issue will seem larger and our reaction to it will be amplified. So try to go in with an open mind, and then work with your clinician to assess your data and let the evidence and the numbers show the difference and make adjustments based on that. You never know when a change can be a great positive that you never saw coming.