Biotech Values

[jellybean]

PGS -- NFLD. After a lot of reading and a little thoughts I can answer some of the questions that were raised regarding Polyheme.

Free hemoglobin has the ability to enter the vascular endothelium where it absorbs NO causing vasoconstriction. Hence, the increase in strokes and heart attacks in patients undergoing surgical procedures. Free hemoglobin also causes kidney damage which can be measured by the level of creatine in the blood.

The mfting process for Polyheme has been developed over a long period of time and results in mixture containing about 99% polymerized hemoglobin that still retains enough flexibility to allow the conformational changes associated with oxygen uptake and release http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_...
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_....
http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=2322034

Of course, there is some free hemoglobin which is why, as David Miller pointed out, the amount transfused into a single patient is limited. Large scale manufacturing has not been attempted, so that will be a concern. Isn't that true of many of these small biotech drugs, though? Look at Discovery Labs as an example of a failure, and Insmed as an example of a success in spite of market negativity.

PhII clinical trial results for trauma victims were promising and showed superiority over saline. However, the trial relied on historical data for the control arm and many of those patients never received any transfusion due to religious or ethical reasons. Therefore, the 30-day outcome for the control patient group is not actually a good reflection of the intended use for this product. The current phIII trial only has to show noninferiority to saline solution. Since the trial is taking place in urban settings where trauma rates are highest (ie violence and car accidents), most patients are within a short ambulance ride to the ER which is also not a perfect reflection of the intended use for Polyheme. Patients in the control arm will be receiving a whole blood transfusion asap. A more realistic trial would be on battlefieleds or in rural emergency cases, however, the cost and time of such a trial would be prohibitive.

The question is then, can immediate transfusion with polyheme and follow up treatment during hemorrhaging for 12 hours post trauma prove equal to saline until the patient can be treated in an ER?

Side effects will be the biggest concern, duhh. 3 interim safety reviews were built into the trial and it is a positive sign with respect to safety that the trial has been allow to continue. The increase in strokes/heart attacks has been reported, but patients also show an increase in creatine levels and bilirubin levels for 3 days following polyheme transfusion. Let's hope none of the patients have kidney or liver issues.