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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