In 2006, the European Medicines Agency granted its first approval of a biosimilar drug, the human growth hormone, Omnitrope™ (Sandoz), and opened the doors of opportunity for this emerging field of medicine. In 2010, President Obama signed into law the Biosimilars Act, and on March 6, 2015, the FDA formally approved its first biosimilar drug, Zarxio™, which is used, among other things, to stimulate the growth of infection-fighting white blood cells in cancer patients. Over the course of just a decade, biosimilar drugs have gained global momentum, driven by the promise to help populations around the world; biosimilars are projected to become a $390 billion market by 2020.
Biosimilars are biological drugs that are highly similar to biotherapeutics, also known as biologics. These complex drugs are made from, or expressed by, a living system, such as a microorganism, animal, plant, or human. They work with the body to address the underlying disease, rather than just the symptoms of the condition. As such, biologics are less toxic than chemically synthesized medicines and hold the great potential to treat many unmet medical needs.
Biologics work in one of three ways:
- Increase the cellular response to a molecule stimulus, known as upregulation (Example: Erythropoietin, a drug that treats anemia)
- Decrease the number of cellular components that responds to an external variable by a process called downregulation (Example: Infliximab, which treats rheumatoid arthritis, among other illnesses)
- Augment the body’s natural defense mechanisms (Example: Factor VIII, which is used to stimulate clotting)
How Biosimilars are Made
A biosimilar drug is made by copying an approved biologic drug — a process similar to the way generic drugs are made after approved small molecule drugs. With generics, small molecule drugs are synthesized by chemical reactions to create a chemical entity. A different company can make this entity in a different facility using the same synthesis methods. Think of this as one-to-one matching.
Although the process to create biosimilars is comparable to generics, it’s important to remember that because biosimilars are made from living hosts, one company’s drug will be inherently different than another company’s drug. This is because small, transient changes that occur in the host cell, or happen during manufacturing, will cause changes in the final product, which is referred to as post-translational modifications. You can find examples of these changes in glycosylation patterns (the way in which a carbohydrate is attached to a hydroxyl or other group), or the different ways that proteins will fold. As such, it’s impossible to make biosimilars identical because there will always be some degree of variance.
Steps to Creating a Marketable Biosimilar
To create a biosimilar, an existing drug is selected as a target and then its chemistry, manufacturing, and controls are replicated. Once the biologic patent is expired or deemed invalidated, the biosimilar can be tested to demonstrate its equivalency to the biotherapeutic drug. This includes any number of in-vitro (in a laboratory bench-top setting) or in-vivo (in live animals) tests where the biosimilar product and the innovator biologic are examined side by side and the results are compared against one another. At the final stages, the two products (the biosimilar and the innovator biologic) may be tested in one or more studies in human subjects, often using patients suffering from a disease to evaluate the therapeutic effect of the biosimilar.
If everything proceeds as planned, the final step is to register the biosimilar for sale in the market. While these steps may appear expeditious to some, each one is complex, costly and time-consuming. Adding to the complexity is the fact that drug approvals and regulations from product to product and from country to country are not standardized — and as such, process efficiencies are certainly lacking.
The Potential of Biosimilars for Health and Business
However, the excitement about biosimilars is building globally because of their power to increase access to life-saving drugs for people around the world — by increasing supply and lowering costs. And because there is no shortage of living hosts, biosimilars will reduce the possibility of drug shortages for necessary medications.
While the cost to produce biosimilars is higher than with generics, and the process for creation much more difficult, these drugs offer greater returns because the tepid competitive environment allows for higher profit margins. As a large number of biologic drugs are going off-patent in the next few years, including Enbrel™ and Humira™, there will be billions of dollars at stake. According to IMS Health, by 2020, biologics are expected to account for 28 percent of the global pharmaceutical market spending, and the biosimilar market will grow to $390 billion. But that’s not the grandest prize.
While biosimilars is a large, high-growth market with increasing worldwide acceptance and infinite opportunity, the potential to increase patient quality of life and promote longevity its real value.
For more on this topic, download the full report, “Biosimilars: An Emerging New Opportunity.”