As reported in today s Wall Street Journal, an FDA advisory panel has voted unanimously to recommend the approval of a new product from Novartis called Zarxio. Assuming that the FDA follows the panel s advice (they usually do), a bit of pharmaceutical history will be made the ability of companies to develop and market biologic drugs that are similar to those of other companies.
Zarxio is a copy of Amgen s Neupogen, which is a protein used to boost white blood cell production and thus reduce infections, primarily in cancer patients who have depleted white blood cells due to chemotherapy.
Amgen, the original inventor, stands to lose much of its $1.3 billion in annual sales if Zarxio gains approval and is sold at a lower price something that is all but guaranteed.
If this sounds like the generic vs. brand drug issue, it is with one additional factor. Assuming that there are no flaws in the manufacturing process, generic drugs are molecularly identical to the brand drug that they have copied. They are simply made by other companies (and sometimes even by the same company). The situation with biosimilars is rather different.
Biological drugs antibodies, proteins, vaccines, etc are very different from traditional pills which are much simpler. The drugs in pills are often called small molecules. They are taken orally, and get absorbed into the blood, where they perform whatever function they are intended to do. They are much cheaper and easier to manufacture and purify than biologics.
Biologics are very large, complex molecules (mixtures, really) that are produced by living entities, usually bacteria. No two batches of the same biologic will even be identical. This is why generic copies of biological drugs are called biosimilars.
ACSH s Dr. Josh Bloom says, A good analogy involves a cake and sugar. Sugar (sucrose) is a small molecule. Every molecule of pure sugar is identical, regardless of how it is made, or isolated. It is very easy to purify sugar by a process called crystallization. A biologic is more like a cake a recipe of ingredients. Even if the same bakery follows the exact same recipe time after time, no two cakes will ever be identical. If a different bakery tries to bake the same cake, it will probably be even more different.
Thus, the composition of any given biologic is highly dependent on the recipe used to make it. Furthermore, biologics are far more difficult to isolate and purify than small molecule drugs. And even a purified biologic will not be homogenous, rather a mixture of very similar components. This is one reason why biological drugs, such as Enbrel (rheumatoid arthritis), Avastin (colon cancer), and Herceptin (certain breast cancers) are more expensive than pills.
Since biosimilars are similar, not identical, the questions become, How similar?, and Does it make any difference? This is a gray area that is not found in pills.
Dr. Bloom explains, The FDA defines biosimilars as highly similar to the original drug, so there is obviously some subjectivity here. This is determined by imperfect analytical methods and clinical performance (efficacy and side effects). So, this becomes a balancing act. Much lower prices in exchange for something that may or may not be as good. This will have to be determined for every potential biosimilar before it is approved.
Uber Blogger Derek Lowe, the creator of the hugely popular In the Pipeline website, has plenty to say about this: Biosimilars are a new world, for sure. You can never be an exact duplicate of the original - just keeping the original like the original is hard enough work as it is. So people will always wonder about the interchangeability of these agents, which will (I think) make the companies bringing biosimilars forward motivated to run head-to-head trials to prove to physicians that their new therapy really can be prescribed without worries.
And, concerning another challenge, Lowe says, The other problem is that without any sort of biosimilar development pathway, the companies developing biological agents have been able to get market lifetimes for their drugs well in excess of the usual patent expirations on small-molecule therapies. And that isn't the intended result of the patent system, either.
The amount of money here is huge. Biological drugs are a $200 billion business, so discounted prices as much as 80 percent less will have an enormous impact on drug costs.
Dr. Bloom s feelings on this matter are fairly clear. He says, I do not even flinch when I take a generic pill instead of the brand. But in the case of biosimilars, I think I ll take the original drug, at least until it becomes evident that there is no material difference.