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Facts about biosimilar biologics

Biologic medications have been a treatment option for patients with inflammatory arthritis for over the past 21 years. Today, there are biosimilar biologic ("biosimilars") versions of originator biologic ("originator") medicines that have lost patent protection. To receive Health Canada's authorization, a biosimilar must demonstrate that it is highly similar and has no clinically meaningful differences in safety and efficacy compared to the originator.[1]

A biosimilar is typically prescribed to patients by a rheumatologist. For example:

  • adalimumab (Amgevita®), adalimumab (Hulio®), adalimumab (Hyrimoz®) and adalimumab (Idacio®) are biosimilar versions of the originator adalimumab (Humira®);
  • etanercept (Brenzys®) and etanercept (Erelzi®) are biosimilar versions of the originator etanercept (Enbrel®);
  • infliximab (Inflectra®), infliximab (Renflexis®) and infliximab (Avsola®) are biosimilar versions of the originator infliximab (Remicade®);
  • rituximab (Ruxience®), rituximab (Riximyo®) and rituximab (Truxima®) are biosimilar versions of the originator rituximab (Rituxan®)

Biosimilars are not generics of their originators
Biosimilars are similar, but not the same, as their originators

Due to the size, complexity and natural variability of biologic medications, and because biologic medications are made in living cells rather than with chemicals, a biosimilar and its originator can be shown to be similar, but not identical.

For example, the way that biologics are manufactured makes it impossible to produce an exact copy of the molecule. This differs from other pill-form medications you may have taken before. Medications like methotrexate and ibuprofen are made of small chemical molecules, not proteins. When patents expire on small molecule medications and generic versions are authorized for manufacture, exact copies can be made.

Biosimilars have been approved for use in Canada since 2009, and for use in inflammatory arthritis since 2014. There are currently 33 biosimilars approved by Health Canada. The European Union approved the first biosimilar in 2006, and in inflammatory arthritis in 2013, and today totals 72 approved biosimilars.

Based on this scientific evidence and real-world data, rheumatologists across Canada are now regularly prescribing biosimilars for inflammatory arthritis patients newly initiated on adalimumab, infliximab, etanercept and rituximab; and in full consultation with their patients, beginning to transition them from their originator to its biosimilar.

Why have biosimilar biologics been developed and approved?

Biologics are treatments that can help patients with serious diseases such as inflammatory arthritis, cancer, diabetes, inflammatory bowel disease and psoriasis. However, they are complex medications and can be very expensive and time consuming to develop. This can limit patients’ access to these medicines, and can make it difficult for the healthcare system to afford them. What does this mean for provincial drug plans? According to data from the Canadian Institute for Health Information, public drug programs spent $14.5 billion in 2018, which accounted for 43.4% of prescribed drug spending in Canada.[2] In 2018, biologics used to treat diseases like rheumatoid arthritis and Crohn’s disease accounted for the highest proportion of public drug spending for the seventh consecutive year.[3]

Like legislated generic drug savings in Canada, biosimilars have the potential to improve patient access to biologics and save public and private healthcare systems billions of dollars now and over the coming years. A study commissioned by the Canadian Government’s Patented Medicine Prices Review Board (PMPRB) has estimated that private and public drug plans across Canada could save from $332 million CDN to $1.81 billion CDN in the third year following biosimilar entry across a portfolio of products.[4]

Why are biosimilar biologics less costly than originator biologics?

A manufacturer of biologics must spend many years studying a new biologic medicine before it can be approved in Canada. The company then holds a patent on the medicine that prevents other companies from selling that product. This allows the originator manufacturer to earn back the money it spent on bringing the medicine to market. When the patent of an originator expires, other manufacturers are allowed to make a biosimilar version of the medicine. Manufacturers that make biosimilars of other originator medicines do not have the same costs to bring the medicine to market and can therefore offer it at a lower price.[5]

What benefits do biosimilar biologics provide patients and our healthcare system?

Biosimilars create three main benefits to patients, the healthcare system, and society:

  1. Savings from biosimilars use can modernize “special access criteria”. Currently, patients must try and fail treatment on older, less expensive medications. Because biosimilars are significantly less expensive, public and private drug formularies can remove the need for patients to fail on these older therapies before approving reimbursement for them;

  2. Savings from biosimilars use can be reinvested into public and private drug formulary budgets making it possible to improve the sustainability of their drug plans by adding new medication listings and boosting existing medicine coverage for patients; and,

  3. Savings from biosimilars can be invested into non-medication elements of care that patients need, such as specialized nursing, counselling as well as, physio- and occupational therapy.

 

[1] Health Canada Biosimilars Fact Sheet

https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/fact-sheet-biosimilars.html

[2] Canadian Institute for Health Information - Prescribed Drug Spending in Canada, 2019, page 7

https://www.cihi.ca/sites/default/files/document/pdex-report-2019-en-web.pdf

[3] Canadian Institute for Health Information - Prescribed Drug Spending in Canada, 2019, page 9

https://www.dropbox.com/s/8axt6loywl9t65r/Screenshot%202020-02-21%2014.51.24.png?dl=0

[4] The Patented Medicines Prices Review Board, Government of Canada. Potential Savings from Biosimilar in Canada poster.

[5] Canadian Agency for Drugs and Technologies in Health (CADTH): Biosimilar Drugs: Your Questions Answered

https://www.cadth.ca/sites/default/files/pdf/biosimilar_drugs_patient_en.pdf

 

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Biosimilar Biologics FAQs

  What is a biologic?

Today in North America, Europe, and Asia, there are more biologics – originators and biosimilars – in use to treat inflammatory arthritis than in any other disease.

Over the past 20 years, biologics have become a life-saving treatment option for inflammatory arthritis patients whose disease does not respond to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) such as hydroxychloroquine or sulfasalazine. 

Biologics are made from living organisms, such as living cells that have been modified using biotechnology. This allows these living organisms or cells to produce the active substance of the biological medicine. This active substance is then harvested from the cells. The active substance is commonly called a “protein.” Biologics made up of proteins are much larger and more complex in nature than conventional, small molecule medicines such as over-the-counter ibuprofen (e.g. Advil) or by-prescription methotrexate. Biologics are administered in two ways; by self-injection under the skin or into muscle, or by intravenous (IV) infusion into a vein in the hand, wrist or arm.

 

  What is a biosimilar biologic?

As patents and data protection expire for originators, other manufacturers may produce new versions of the biologic medicines called biosimilars. To receive Health Canada approval, a biosimilar must demonstrate that it has similar effectiveness, safety, immunogenicity profile and quality, and delivers the same therapeutic benefits to patients as its originator.[1]

Biosimilars have been approved for use in Canada since 2009 and for use in inflammatory arthritis since 2014. Thirty-three biosimilars are currently approved by Health Canada.

  What is an originator biologic?

An originator biologic is a medicine that has been approved for sale by Health Canada. It is also called a “reference” biologic because it is the medicine to which a biosimilar is compared by Health Canada during the approval process for a biosimilar.

  Are biosimilar biologics generic biologic?

Generic medications are copies of brand-name medications, have the same active ingredient, and are the same as those brand name medications in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use.

If they meet Health Canada's safety and efficacy requirements, biosimilars are allowed to enter the marketplace when the patent of the originator expires. Biosimilars, like generic medications, are lower priced versions of brand name drugs and are approved through abbreviated pathways that avoid duplicating costly clinical trials. But biosimilars are not the same as generic medicines because unlike non-biological medicines, biologics cannot be exactly copied. Biosimilars and their originators can be shown to be highly similar, but not identical. This is because biologics (biosimilars and originators) are often large and complex and are made from living cells rather than with chemicals and so are naturally variable.

  What is immunogenicity?

The immune system has evolved to recognize foreign proteins in the body. Biologics are usually injected into the body and the immune system often reacts to them. This reaction is referred to as the immunogenicity of the product. Sometimes immunogenicity can only be detected using sophisticated laboratory tests and has no impact on the patient. In other cases, immunogenicity can impact patient safety or how well the medication works. For these reasons, studies showing that there are no clinically meaningful differences in immunogenicity between the biosimilar and originator are required for authorization of a biosimilar. In addition, biosimilar manufacturers are responsible to monitor the immunogenicity potential of the biosimilar after it is used in Canada.[1]

  What is interchangeability?

In Canada, interchangeability often refers to the ability for a patient to be changed from one drug to another equivalent drug by a pharmacist, without the intervention of the doctor who wrote the prescription when it has been deemed interchangeable by a Provincial or Territorial regulatory body. For instance, this is a common practice for drugs that are off patent and have been deemed interchangeable with their generic equivalent.

For example, say a patient self-administers a biologic medication by injection to treat their rheumatoid arthritis. To receive the biosimilar instead of the reference product, the patient needs a prescription from a rheumatologist written specifically for that biosimilar. However, once a product is approved by Health Canada as interchangeable, the patient may be able to take a prescription for the reference product to the pharmacy and, depending on the Province or Territory, the pharmacist could substitute the interchangeable product for the reference product without consulting the rheumatologist. 

At present and as it relates to biosimilars, Health Canada has declared biosimilars not to be interchangeable with their originator. Health Canada's authorization of a biosimilar is independent of provincial, territorial, or private drug plan decisions regarding its formulary listing and reimbursement or any decision as to interchangeability between these drugs. According to the new guidance from Health Canada, interchangeability decisions rest with provincial or territorial governments. They also regulate pharmacy substitution practices.

  What does “transitioning” or “switching” mean?

”Transitioning” or “switching” means a patient is moved from one medication to another. In the case of biologics, there are two types of transitions:

“Medical transition” occurs in the case of a patient not doing well on their current originator biologic or biosimilar biologic who is transitioned to another originator or biosimilar, based on a decision by the patient and their rheumatologist, in order to regain maximum disease control.

“Policy transition” (sometimes referred to as “non-medical switching”) occurs when a public or private drug plan’s reimbursement policy necessitate patients move from their current originator biologic to its biosimilar biologic.

Are patients being transitioned to biosimilar biologics in Canada?

For the past six years, provincial drug plans across Canada have listed biosimilar brands ahead of originators for treatment-naïve patients (patients who have not previously received the originator). Since 2019, some provincial drug plans have also begun implementing biosimilar transition policies that change coverage for specific biologic medicines.[1] Under a transition policy, patients and their prescribers have a certain period to discuss transitioning from an originator brand to a biosimilar brand. Patients unable to transition or who have an adverse response to the biosimilar can seek exceptional “special authority” coverage for the originator.[2]

Prior to switching, both physicians and their patients must be fully informed and have all available information about the biosimilar medicine, such as details about the reimbursement policy, patient support program information, including contact names and phone numbers.

Health Canada’s position on transitioning

In the context of biosimilar use, Health Canada considers “switching between authorized products to refer to a change from routine use of one specific product to routine use of another specific product. Patients and healthcare providers can have confidence that biosimilars are effective and safe for each of their authorized indications. No differences are expected in efficacy and safety following a change in routine use between a biosimilar and its reference biologic drug in an authorized indication.”[3]

What is the NOCEBO effect?

Transitioning patients from originator biologics to biosimilar biologics is associated with the potential for a “nocebo” effect, a phenomenon that occurs when a patient’s negative expectation causes a treatment to have a more negative effect than it otherwise would—essentially, the opposite of the placebo effect.

The way in which rheumatologists and other healthcare providers communicate with patients about transitioning to a biosimilar is key to preventing the nocebo effect. Patients should be informed about the transition well in advance, and the availability of research-based information is important for patient understanding and empowerment. Finally, an appointment with a rheumatologist to discuss biosimilar transitioning should ideally allow enough time with the patient to understand the concept of biosimilars and transitioning and to address any concerns properly.

  What is extrapolation?

Because of the way biosimilars are developed, it is not always necessary to carry out clinical studies with the biosimilar in all the diseases for which the originator has been shown to work. Instead, it may be possible to extend safety and efficacy data from studies in one disease to cover others. This is known as extrapolation or extension of indications. An indication is a term that means the use of a medicine to treat a specific disease. Many biologic medicines are authorized for more than one indication.

Because a biosimilar is very similar in structure and function to an originator with proven safety and efficacy, clinical studies do not need to be repeated for each indication.

Patients and physicians can have confidence in the use of a biosimilar in each indication approved by Health Canada. 

Questions about biosimilars research? Let us find the answers for you.

As biosimilars research data continues to be published and policies regulating them evolve, ACE continues to provide information for the arthritis community. As part of that commitment, we encourage you to send us questions. We will provide answers to you and add that content to our website. That’s what the Biosim•Exchange is all about.