Franksja, I have the article since first published, since then I have been quoting it.
First check the editorial that follows immediately the article in the next page, if not available ask xoma to provide it, if not I will find it later, in the meantime just know the editorial says :it did not work.
The use of antibiotics is almost generalized, and this does not mean infection, most is preventive. xoma's goal was to prevent or heal beyond the use of antibiotics which are known safe, effective, and CHEAP drugs. xoma is asking to add $3,000 to $8,000 to this protocol, and what does a clinician get for it? nothing.
One should read pII infectious complications the more specific way and stratified:
1. bacteremias (proven in blood culture)is a very clearcut finding, but numbers range from 4% to 8% (1 in 20, to 1 in 10) this makes the trial they way is design an almost sure failure (and it did failed in pIII) unless xoma aims for 20,000 patients (way expensive)
If xoma could screen (lps is xoma technology)and tailored to most chances for infection group they could do it with less patients, but more centers and/or more time needed, more expensive too (and too late now).
1ry bacteremias were not prevented, worse neither were 2ry bacteremias and this is OMMINOUS and my biggest worry about bpi future in acute sepsis.
2. Local infections: no difference, and this is a bad (not omminous) finding too.
3. "pneumonia" : this is a big messy area (not xoma creation), How was pneumonia diagnosed? clinical? ten clinicians will not agree in same patient, x-rays? ten radiologists will not agree in same patients, culture? got to get clinicians to agree how to take the sample, biopsy? sure not biopsy, too invasive, is a very difficult subject, pneumonias could be from many causes: trauma, inflammation, local trauma, bacteremias, oxygen damage (like ards), excess fluid, lack of perfusion (hypotension damage) due to blood loss, aerosols from other patients and staff, viruses, drugs (legal and illicit), fracture bones fat, embolisms, clots, dic, even just letting the patient lying back in same position will create atelectasis and dependent edema similar to pneumonia, and yes gram positive bacteria!!!
In a good protocol all this variables will be controlled to minimize confounding, and in Vienna they talked about 50% decrease in certain "events". Well, something as simple as a strict protocol of changing patients position during the ICU stay (more strictly followed under research conditions)
control in the use of oxygen by protocol, and one will get the decrease in "events"
Remember Synergen pIII in septic shock? it was the same claim: placebo events decreased beyond what was expected, the results: From $60 to $0.5 when it was finally takeover.
The pII article did not hype, but xoma did, they pr highly optimistic (george did no like it at the time), got the $25 millions and party to pIII, they clearly talk the "big indication" unrestrained and got the $18 million from Sutro, that is not even my problem, is the life of the market, I could not care less, my job is to gauge the results, for a while it was that shares got to $8.
My doubts started when I saw the full pII and I started to look critically at the numbers, it was clear that going into pIII was an expensive, risky martin research,
my prediction was clear: "hope that DSMB in Sept says its safe keep going" it was safe, but no efficacy, DSMB halted.
xoma is now force to focus bpi in for infections.
bpi IF good for infections will be a great drug, just now I do not have evidence that this is so, I will be in the safe side out of the stock.
xoma could look at the data hard for months, pIII is not design to produce good data for the low event levels (5% bacteremia)then they will find nothing but failure. |
