Ben Locwin, Healthcare Science Advisors06.02.15
Some great products and services have been done a disservice by being named something that either didn’t conjure a sufficiently-vivid mental picture of what they were or did, or they had mostly accurate lexical names that didn’t have a sticky quality to them, and the market didn’t respond. Unfortunately, the moniker ‘biosimilar’ is somewhere along the spectrum where those in the industry have a concept of what it means, but in practice it has very little meaning to the general public.
With direct-to-consumer marketing of prescription drugs worth billions of dollars per year in the U.S., most people understand that ‘generic’ refers to a cheaper version of ‘expensive’ drugs; the two names are almost synonymous. When I asked a sample of 12 people—who passed a qualifying test of correctly answering what a generic drug meant—what a biosimilar was, 0 respondents (0%) had a correct understanding, and 3 respondents (25%) hedged a guess that it was something that had a similar effect in different people. This is, from a public health perspective, an interesting take; though biosimilar refers to the similarity of the resultant molecule compared with the original product, this should give a similar effect in vivo. This however is a non sequitur logical fallacy: From Latin “it does not follow” that a similar molecule will necessarily have similar function or efficacy, with similarity (i.e., non-identicality) becoming more possible with larger and more complex molecules. A common example of this is ethyl alcohol that we drink compared with ethylene glycol, which is very toxic. Without knowing much about the molecular conformations, these two molecules look very similar.
This has become the difficult philosophical regulatory question: therapeutic molecules are produced similarly, how similar is enough? It was once conventional wisdom that biosimilars couldn’t even be produced. It was thought the molecular complexity was just too high that it wasn’t a viable option to pursue. But production and analytical technologies have advanced dramatically in just the past two decades. Interestingly though, while generic drugs have to be chemically identical and show bioequivalence, biosimilars need to have a high degree of similarity to the innovator product and are considered to be biologically and clinically comparable. This leaves many large sources of error variance in our ability to do like-for-like comparisons within the market.
How Will We Measure?
In order to bring less-expensive therapies to those in need, the ethical response should include biosimilars in its toolkit; it doesn’t solve every problem, but it should certainly not be eliminated from consideration. However, if we look at side effect profiles between the innovator product and its biosimilar, what do we do when (not if) we detect differences? What if, over hundreds or thousands of patient-years of exposure, the number-needed-to-treat (NNT) or number-needed-to-harm (NNH) are different between the platform therapy and its biosimilar? These data will manifest soon, and being able to respond intelligently to the questions is simply prudent, smart business, and good pragmatic science. How different does different have to be before we send alert signals?
Regulatory Track Record: It Has to Start Somewhere
We have just entered a disruptive era in medicines regulation—the first FDA-approved biosimilar, Zarxio (Novartis), received clearance on March 5. This is a biosimilar of Amgen’s Neupogen. Much of the industry is waiting for this regulatory track record to be built-up so that further approvals can come more quickly. This is the same sort of regulatory paradigm as that facing plant-based antibody production, where therapeutic antibodies are produced within plant cells. The first plant-based recombinant therapeutic protein, Elelyso, was approved in 2012. The lack of a prior regulatory track record, in a market dominated by a long line of successes in mammalian cells, has kept funding capital and prospective therapies from plant cells relatively modest.
Biosimilars are currently an average of about one-third less expensive than their platform biologics where they are already available. Similar with the pricing structure of generics relative to brand-name drugs, this ratio could become something more like 90%+ less expensive in coming years.
So as it is with biosimilars being, well, “similar”, the strategic posture will need to be one of deciding how much signal is different enough to do something about or leave alone. Additionally, there’s a great deal of value in revisiting the ethical gray space of monitoring safety and adverse events, but doing it in the context of being able to reach a broader population of patients potentially in need of lower-cost therapies.
Ben Locwin
Healthcare Science Advisors
Ben Locwin, PhD, MBA, MS writes the Clinically Speaking column for Contract Pharma and is an author of a wide variety of scientific articles for books and magazines, as well as an acclaimed speaker. He also provides advisement to many organizations and boards for a range of healthcare, clinical, and patient concerns.
With direct-to-consumer marketing of prescription drugs worth billions of dollars per year in the U.S., most people understand that ‘generic’ refers to a cheaper version of ‘expensive’ drugs; the two names are almost synonymous. When I asked a sample of 12 people—who passed a qualifying test of correctly answering what a generic drug meant—what a biosimilar was, 0 respondents (0%) had a correct understanding, and 3 respondents (25%) hedged a guess that it was something that had a similar effect in different people. This is, from a public health perspective, an interesting take; though biosimilar refers to the similarity of the resultant molecule compared with the original product, this should give a similar effect in vivo. This however is a non sequitur logical fallacy: From Latin “it does not follow” that a similar molecule will necessarily have similar function or efficacy, with similarity (i.e., non-identicality) becoming more possible with larger and more complex molecules. A common example of this is ethyl alcohol that we drink compared with ethylene glycol, which is very toxic. Without knowing much about the molecular conformations, these two molecules look very similar.
This has become the difficult philosophical regulatory question: therapeutic molecules are produced similarly, how similar is enough? It was once conventional wisdom that biosimilars couldn’t even be produced. It was thought the molecular complexity was just too high that it wasn’t a viable option to pursue. But production and analytical technologies have advanced dramatically in just the past two decades. Interestingly though, while generic drugs have to be chemically identical and show bioequivalence, biosimilars need to have a high degree of similarity to the innovator product and are considered to be biologically and clinically comparable. This leaves many large sources of error variance in our ability to do like-for-like comparisons within the market.
How Will We Measure?
In order to bring less-expensive therapies to those in need, the ethical response should include biosimilars in its toolkit; it doesn’t solve every problem, but it should certainly not be eliminated from consideration. However, if we look at side effect profiles between the innovator product and its biosimilar, what do we do when (not if) we detect differences? What if, over hundreds or thousands of patient-years of exposure, the number-needed-to-treat (NNT) or number-needed-to-harm (NNH) are different between the platform therapy and its biosimilar? These data will manifest soon, and being able to respond intelligently to the questions is simply prudent, smart business, and good pragmatic science. How different does different have to be before we send alert signals?
Regulatory Track Record: It Has to Start Somewhere
We have just entered a disruptive era in medicines regulation—the first FDA-approved biosimilar, Zarxio (Novartis), received clearance on March 5. This is a biosimilar of Amgen’s Neupogen. Much of the industry is waiting for this regulatory track record to be built-up so that further approvals can come more quickly. This is the same sort of regulatory paradigm as that facing plant-based antibody production, where therapeutic antibodies are produced within plant cells. The first plant-based recombinant therapeutic protein, Elelyso, was approved in 2012. The lack of a prior regulatory track record, in a market dominated by a long line of successes in mammalian cells, has kept funding capital and prospective therapies from plant cells relatively modest.
Biosimilars are currently an average of about one-third less expensive than their platform biologics where they are already available. Similar with the pricing structure of generics relative to brand-name drugs, this ratio could become something more like 90%+ less expensive in coming years.
So as it is with biosimilars being, well, “similar”, the strategic posture will need to be one of deciding how much signal is different enough to do something about or leave alone. Additionally, there’s a great deal of value in revisiting the ethical gray space of monitoring safety and adverse events, but doing it in the context of being able to reach a broader population of patients potentially in need of lower-cost therapies.
Ben Locwin
Healthcare Science Advisors
Ben Locwin, PhD, MBA, MS writes the Clinically Speaking column for Contract Pharma and is an author of a wide variety of scientific articles for books and magazines, as well as an acclaimed speaker. He also provides advisement to many organizations and boards for a range of healthcare, clinical, and patient concerns.
