Sunday, January 25, 2015

Biotech Failings, Ear Infections and Generic Drugs from India.

Several news articles caught my attention this past week.  One dealt with the antibody cocktail for the treatment of Ebola (Andy Pollack was an important source of information here).  I note that I have managed to avoid the entire Ebola news cycle since I’m more of an antibiotics person than an epidemiologist or virologist.  But Andy’s article reminded me of something I wrote about in my book five years ago.  Biotechs, with a few notable exceptions, are notoriously bad at thinking about manufacturing their potential products during the early stages of their development.  This oversight can lead to severe problems and long delays later.  That is exactly what appeared to happen to ZMapp and its partners including BARDA (Biomedical Advanced Research and Development Authority – an agency of HHS). ZMapp, if you don’t remember, is a biotech company that had discovered a mixture of antibodies that could cure Ebola in a monkey model of infection.  Their product was actually used to treat a few patients. Whether it works in humans or not is anybody’s guess since no actual trials were ever carried out and patients do recover from Ebola spontaneously in 30-60% or so of cases. But the company’s idea of manufacturing was to use genetically engineered tobacco plants.  This idea is not new – we were talking about this in Wyeth in the 1990s. But so far, no marketed product has ever been manufactured this way since achieving the scale required for commercialization or even decent clinical trials has never yet been achieved.  But this is where ZMapp placed its future.  When BARDA partnered with ZMapp, one of the first things the BARDA scientists did was to explore other modes for manufacture.  All this takes time and it is not even clear that even if they were to use a more traditional method (like CHO cells for e.g.), the resulting antibodies would have the same activity.  Therefore, the new antibodies might have to be tested once again in the monkey model.  How many years of delay is this?  I don’t know, but to me this is another great example of the shortsightedness of biotech when it comes to manufacturing their products. 

On the ear infection front, another placebo-controlled trial was just published in the Journal of the American Medical Association. First, I need to remind you that two such trials were published several years ago looking at the clinical cure, relapse and complication rates of antibiotic vs. placebo treatment of acute middle ear infections.  Both trials definitively showed that antibiotics have a substantial treatment effect to the point where the FDA now allows non-inferiority trials of ear infections once again. The new data published in JAMA were obtained during trials that were carried out before and during the earlier trials.  This is important since it is becoming highly questionable whether it remains ethical to withhold therapy from children with well-documented acute middle ear infections. The trial was carried out in Finland – like one of the earlier trials.  These new data show that the antibiotic-treated children had an impressive rate of resolution of the middle ear fluid that builds up during the infection compared to those that received no antibiotic therapy.  This also may be associated with a lower rate of hearing loss in the treated children according to the authors. While I agree that these new data are of potential value to physicians considering whether to treat children with antibiotics or not, I think that it is long past time to stop initiating placebo-controlled trials of antibiotic treatment of such children.

Finally, Europe has banned a 120-page list of generic drugs manufactured in India by Abbott Laboratories, Actavis, Dr. Reddy's Laboratories, Mylan Pharmaceuticals, Sandoz, Takeda Pharmaceuticals and others.  The reason for this ban is that, according to French inspectors, a contractor called GVK biosciences manipulated the EKG data of subjects during studies to show that the generic drugs were equivalent to the branded products in question. While it is unlikely that this actually would affect the health of patients taking these drugs, it is more evidence that India, as the world’s largest and possibly least expensive manufacturer of drugs, is also the most perilous place to carry out such production.

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