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By Dr Nigel Umar Beejay MB BChir, MA (Cantab), FACP, CPE, Dip (Med Hyp), Consultant Physician, Gastroenterologist and Hepatologist, Certified Physician Executive, Advanced Center for Daycare Surgery, Abu Dhabi, UAE; Harley Street, London UK
Over the last few years a new phenomenon potentially worth more than $390 billion USD by 2020 has begun to transform the traditional pharmaceutical marketplace with the development of a new form of “designer drug” class called biosimilars. Biosimilars are “near exact” copies of patent protected drugs that effectively offer the same benefits of the original patent-protected drugs in terms of effectiveness and safety. Most importantly, biosimilars are priced significantly lower than the original drug and can be manufactured without the threat of patent infringement. So important is this phenomenon that it has been estimated by QuintilesIMS, a leading healthcare intelligence organisation, that biosimilars will account for up to 28% of the value of the global pharmaceutical market by 2020. Biosimilars will be a huge game changer in the overall cost of drugs now and in the future.
Drivers in the Development of Biosimilars
Healthcare is a costly business and the significant costs associated with drugs have been a major driver in the development of the biosimilar market. According to a recent report issued by the US Centers for Medicare and Medicaid Services' (CMS) Office of the Actuary (OACT), total healthcare spending in the USA for 2016 was $3.4 trillion USD and is currently predicted to rise rapidly by 5.6% annually over 2016-2025. In fact, healthcare spending is predicted to account for up to 19.9% of the US GDP by 2025 with 47% of spending being financed by the US government. Moreover, prescription drug spending has been projected to grow an average of 6.3 percent per year from 2016 to 2025.
What are Biosimilar Drugs?
Biosimilars are drugs which are chemicals which are very similar in structure to original drugs but not exact copies. Many drugs are made up of complex arrangements of chemicals, many of which can adopt a 3-dimensional shape. Even a simple compound such as water (made of 2 hydrogen molecules and 1 oxygen molecule) has a 3-dimensional ‘V’ shape. The shapes of drugs can affect their interactions very specifically in a similar way to how a key fits only one lock. So the shape of the drug can help determine its action(s).
While most drugs are usually small molecules made through bio engineering, biologics drugs have a much more complex shape and structure and are often created by genetically engineered organisms such as yeasts and bacteria.
So a biosimilar drug is a near copy of an original approved biologic drug, the so-called “reference product”. The biosimilar drug often has a three-dimensional shape and other properties that allow it to open the same lock that the original “reference product” drug opens. For example, in the case where there is a drug made of 3000 atoms joined together to make a molecule which does something in the human body like reduce inflammation, a biosimilar drug may be a near exact copy of the original drug with only one atom changed. This new structure, even if it differs by only 1 of the 3000 atoms that made up the original “reference product” drug, is now a completely different drug which is off patent and is not owned by the pharmaceutical company that developed the original “reference product” drug.
What Conditions are Treated by Biosimilars?
The medical diseases treated by biosimilars are numerous and expanding. They include diabetes, anemia, polycystic ovarian syndrome, rheumatoid arthritis, Non-Hodgkin’s lymphoma (NHL), neutropenia, venous thromboembolism and osteoporosis.
The most popular biologic therapy in the world is Humira®, a patented drug used to treat a number of immune mediated diseases, some of which include rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn's disease, amongst others. Global sales estimates for Humira® in 2017 are around $16 billion USD. Recent estimates have suggested that the introduction of Imraldi®, a biosimilar to Humira® in Europe could result in savings of $3.18 billion by 2020 even though Imraldi® was only approved in August 2017.
How are Biosimilars Different from Generic Drugs?
Drug development is a long and very costly enterprise so to protect their return on their investment, pharmaceutical companies patent their new drugs to prevent other companies from copying the drug. The original patent usually lasts 20 years. After a patent expires, other drug manufacturers can make exact copies of the drug and market them without facing the threat of a patent infringement lawsuit. These exact copies are called generic drugs. An example of a previously patented drug is Nexium®, a drug used to control acid production in the stomach and thereby treat acid-related diseases. The generic form of Nexium® is omeprazole and this generic drug was manufactured by many pharmaceutical companies once the patent for Nexium® expired.
Biosimilars are not exact copies of patented drugs while generic drugs are exact copies. By creating “near exact” copies of patented drugs, biosimilars can sidestep patent challenges and bring to market drugs that have essentially the same clinical and safety profile.
There is also a significant difference in the cost of developing a generic drug versus a biosimilar. Generally speaking, it might take three to five years to develop a generic drug at a cost of up to $5 million USD. On the other hand, biosimilar development would take 7-10 years with a projected cost of up to $250 million USD.
The Biosimilars Upside: Same Drug for a Lower Price
The bottom line is price. Biosimilar drugs can be produced by several manufacturers and usually at a more cheaper rate. The company that manufactures the biosimilar drug has essentially taken a drug that may have taken many hundreds of millions of dollars to create, develop, manufacture and test in clinical trials, altered it ever so slightly and then marketed it as a near equivalent product. The bottom line is that the patient gets a drug with similar effect and safety but at a cheaper cost.
What is the Downside to Biosimilars?
First of all, biosimilars are not easy to make. Secondly, because they are the slight variation of an original drug they are still required to undergo extensive testing. As an example, for Zarxio® (filgrastim-sndz)—a biosimilars drug that is used to treat low blood neutrophil levels—to be approved, Sandoz had to show data from 388 people with breast cancer as well as 174 healthy volunteers to show that the drug was broken down in a similar way to the original drug.
In addition, a number of concerns exist about the safety of biosimilars. One concern suggests that biosimilar drugs may not be subject to the same level of scrutiny as the original drugs. In addition, given the relatively new development of biosimilars, concerns exist about their potential long-term safety.
A further concern surrounds the regulation of biosimilar post-marketing surveillance. When a pharmaceutical company invests hundreds of millions of dollars in drug development, they are duty bound to monitor the drug’s safety after it has been launched and is being used by patients. This process is called post-marketing surveillance and is an extremely useful method of detecting potential problems with drugs that might crop up so sporadically that they were not detected during drug development. Biosimilar post-marketing surveillance is still being developed to ensure that the process is robust.
Approval and Regulation of Biosimilars
The process of approval and registration of biosimilars has been much faster in Europe than in the USA and currently the USA lags Europe by up to 10 years in the biosimilar market. While over 36 drugs are currently listed as biosimilars by the European Medicines Agency (EMA) only 7 have been approved by the US Food and Drug Administration (FDA) as of October 2017.
The process of approval and registration is complex and has to go through many steps. It was as late as early 2010 that Biologics Price Competition and Innovation Act (BPCI Act) was signed into US law. It was this regulatory law that allowed the US FDA to begin the process of evaluating this new class of drug.
The first biosimilar authorised in Europe by the EMA in April 2006 was Omnitrope® (somatropin), a biosimilar manufactured by Sandoz GmbH, and designed to help in conditions where there is growth hormone deficiency. The newest authorisation from the EMA was issued as recently as August 2017 for a drug called Imraldi® (adalibumab) manufactured by Samsung Bioepis UK Limited (SBUK). This biosimilar can be used to treat over 11 immune mediated diseases including rheumatoid arthritis, Crohn's disease, ulcerative colitis, plaque psoriasis and polyarticular juvenile idiopathic arthritis.
While the first biosimilars to be approved by the FDA appeared in March 2015, the European EMA had approved the same drug six years before in 2009. This first biosimilar licensed in the USA was a drug called Zarxio® (filgrastim-sndz), produced by Sandoz®. Zarxio® works to help prevent infection by stimulating the growth of neutrophils, a type of white blood cell.
Although the US has got off to a slow start, it is expected that the biosimilar pipeline will ramp up considerably in the next few years. Biosimilars can be fast track approved by the FDA in the USA if it can be demonstrated that the biosimilar is “highly similar” to an already-approved biological product and demonstrates no significant differences from the originally approved reference drug in terms of clinical effectiveness and safety.
More importantly, once a product is deemed a biosimilar, it enables a pharmacist to substitute any biosimilar for the original products without checking with the doctor who prescribed the original drug.
The Future is Rosy for Biosimilars
As human beings live longer and the population demographics change, healthcare costs will inevitably rise. These costs have been a direct driver in the development of the biosimilars. Each year, more biosimilars will be developed to try to curtail ever spiraling health care costs while offering the surety of similar clinical benefits and safety profiles of patented drugs. One thing is certain, biosimilars as a drug class as here to stay and their future looks very promising.