Biosimilars and Complex Generics Uptake Not as Expected – Why is that a Surprise?

Many articles had decried the fact that biosimilar uptake is not what FDA or the drug industry anticipated.  Look, I have been around in this industry in one form or another (pharmacist, regulator, and consultant) for 46 years and have seen a lot in my day.  They say history repeats itself – no I am not planning to go back to FDA – but the same concepts and forces are in play today as they were when Hatch-Waxman (H-W) was first passed.  What concepts and forces you may ask? The concept and force of fear and the unknown.  Let me explain.

When the push for new post-62 generics became a shove after H-W became law, the brand name industry undertook an all-out PR campaign against generic products.  There is no way the generic could be as good as the brand name product, there may be a problem with the generic because this product should have a brain-wave-study to establish bioequivalence.  Extended-release products are so different than immediate release products.  There are numerous other study points, metrics and considerations that must be taken into account – just to name a few of the arguments raised by innovators in the early days of H-W.

In addition, there was an entire generation of physicians that lived through the digoxin and potassium chloride or other marketed, unapproved drug products that had mortality and morbidity issues associated from these very old generic products that, by the way, were manufactured under less than optimal quality conditions.  Also, patients were very skeptical of the quality and “sameness” of generics and wanted to continue to take their brand name drugs.  People associated generics with a lesser quality (for instance who wanted to use a “generic” toilet paper?)

It took a long time for the generic program to build the public’s confidence in the approval and quality of generic versions of brand name drugs.  But even today there are skeptics.  Why would one think that for complex generic and biosimilars that the medical community and patients would not have the same skepticism?  When complex drugs like enoxaparin and copaxone hit the market, generic uptake was much lower than expected (it certainly did not come close to the 90% uptake for many simpler generics.  It takes time for the comfort level to rise to a point of confidence in the approval process for such products.

I was once told by a respected FDAer, who will remain anonymous, that before trying a newly approved NDA drug for hypercholesterolemia that I should wait at least 5 years until we see what side effect emerge once the drug is available in the general population.  These attitudes are hard to change, and any failure or problem with an approved generic product causes a seed of doubt to grow in the health care community or general patient population.  Just imagine how the latest valsartan impurity issue will impact the confidence of those patients in the FDA and the generic drug review process.  One step forward and two steps back!

So, in my opinion, it should come as no surprise that the uptake of complex generics and/or biosimilar drugs will increase at a much slower rate than might be expected for other types of “generic” products.  The proof will be in the long run – remember at the time of passage of Hatch-Waxman generic substation was 19%, now it is at 90%.  Healthcare providers and patients are being cautious.  What else would you expect with something new and very complex.  I believe it will improve, but only after physicians see sufficient experience that bears out that the biosimilars are as safe and effective as their brand name counter parts (and don’t forget that there have been no biosimilars that have been approved as interchangeable yet).  Same thing with complex generics, as experience and confidence gains so will the market share of those products.