10 Things You Should Know about Biologics and Biosimilars

I have been presenting on biologics and biosimilars for the last year and I have been surprised in the interest in the topic and how little many healthcare professionals know about these important medications. Here are 10 things that all healthcare professionals should know about biologics and biosimilars.

1.      Biologics Transformed Chronic Disease Management

For many conditions, such as rheumatoid arthritis (RA), inflammatory bowel disease, and plaque psoriasis the introduction of TNF-alpha’s and other immunomodulators transformed treatment. These products:

• Reduce disability
• Improve quality of life
• Dramatic change in the health of patients

I was practicing in the pre-biologic era and saw how conditions such as RA led to incredible pain and disability for the vast majority of patients. The introduction of biologics provided patients with such hope that they could control their conditions.

2.      A Biologic is Grown and Not Synthesized

A biologic is not a chemically synthesized drug. It is manufactured from animals, or microorganisms, or through the use of, animals, or microorganisms. It not only includes monoclonal antibodies but also:

• Insulin
• Vaccines
• Cytokines
• Protein hormones
• Gene therapy products

One of the easier ways to envision biologics, is they are closer to growing a crop in a farmer’s field than a reaction by mixing a number of chemicals. Biologics are typically grown, harvested, purified and modified. This is very different from making a drug like Aspirin® which can be done by combining the right chemicals in the lab.

3.      Biologics are Massive Molecules

The molecular weight Aspirin® is 180 Daltons.

The molecular weight of a small biologic like human insulin is 5,808 Daltons. When we look at monoclonal antibodies, they are 150,000 Daltons or almost 100,000 times the molecular weight of Aspirin®.  An easy an analogy is that the complexity of Aspirin® is like a skateboard, where a monoclonal antibody is like a jumbo airliner.

4.      Biologics are a Major Drug Cost Driver

From strictly a cost per day perspective, biologic therapies are costly compared to traditional medications. They significantly alter the course of many disease states and could lead to lower costs such as additional physician visits, hospitalization and complication management. It is important that we look at healthcare as a big pie and not the silos for drug, hospita, and professional services.

We also have to remember that the drugs have a major impact on the quality of life of individuals which is tough to attach a dollar figure to.

5.      The Biologic Market is Growing

The first biologic agents were just for a few conditions. Immunotherapy is a rapidly growing in the management of many conditions and is starting to be used much more frequently in oncology to target specific markers for various cancer types.³

We are going to see an ever-increasing number of specialty drugs that will be marketed for a handful of your patients.

6.      Biosimilars are Here to Stay

Several biosimilars have been launched in Canada. A biosimilar is defined by Health Canada as:

• “A biologic drug that obtains market authorization subsequent to a version previously authorized in Canada, and with demonstrated similarity to a reference biologic drug. A biosimilar relies in part on prior information regarding safety, efficacy and effectiveness that is deemed relevant due to the demonstration of similarity to the reference biologic drug and which influences the amount and type of original data required. Biosimilar biologic drugs were previously referred to as Subsequent Entry Biologics.”

Some key things from this definition:

1. They are similar but not identical to the refence biologic
2. They rely on some of the safety and efficacy data from the reference biologic

7.      Biosimilars have a Different Approval Process than Generic Drugs

When a medication loses its patent protection another company is allowed to develop this medication. The approval of generic medications and biosimilars in Canada are very different.

For standard generics, there is no efficacy or safety trials required for approval. Typically, one strength of the generic drug is pharmacologically tested in small group of healthy volunteers. The max blood level (Cmax), time to maximum blood level (Tmax) and area under the concentration curve (AUC) must fall within a Health Canada specified range. If these parameters are within this range, the drug is approved for all of the indications of the reference drug.

Biosimilars are similar but NOT identical to the reference biologic. Health Canada requires the biosimilar company to test the efficacy of the biosimilar versus the reference biologic in patient groups that would be likely treated by the drug.  It is a trial that assesses for similar efficacy and safety as the originator.  If this occurs, the biosimilar may be approved for some or all of the indications of the reference biologic.

8.      Biosimilars are NOT Generic Biologics and NOT substitutable

As I have presented on the topic, many pharmacists are under the belief that when a biosimilar comes to market that all patients can be changed from the reference biologic to the biosimilar. This is not the case. Health Canada, the FDA and the EU do not endorse non-medical substitution.

Currently if a patient is on the reference biologic they should not be automatically changed the biosimilar.  The reverse is also true, and you should not go from the biosimilar to the reference biologic or another biosimilar.

9.      Extrapolation of Indication

One of the biggest issues with biosimilars for some clinicians is the extrapolation of indications. For example, the initial trials to approve one of the biosimilar infliximab were tested in patients with rheumatoid arthritis. This demonstrated a similar response and safety to the reference biologic.

The biosimilar was not tested in inflammatory bowel disease, but was given the indication even though they did not have trials to support its use in these populations.

That being said, the current data has not demonstrated an issue in using the biosimilar infliximab with these other indications.

10. Immunology with Biologics versus Biosimilars

Another concern that is raised with biosimilars is the potential increase in immunogenicity. The body can develop antibodies to biologics. When significant amount of antibodies form, treatment failure normally follows. There are concerns that the differences in the structure of the biosimilar can lead to an increase in immunogenicity. More information on this possible concern will become available as an increasing number of biosimilars come to market.