Dear Todd,
I have not read Paul Kelly's opinion about blood substitutes, but I am aware of his totally negative comments about all blood substitutes,including rHb 1.1 of Somatogen.
(1) His point about short half life is valid to a degree. Free Hemoglobin solution has half life of several hours, rather than days. Any molecule, less than 54000 daltons molecular weight is filtered by the Kidneys. However, this solution is still very useful in emergencies and in operatin rooms.
However, science already has solutions to this problem. Many small molecules are combined with PEG-Poly Ethylene Glycol. The combined molecule is heavy and can't be filtered by the kidneys, prolonging their half life to several days. All Hemoglobin solutions: Baxter, Northfield have same problem.
Fully aware of this problem, Somatogen already has 2 more genetically engineered Hemoglobin molecules of higher molecular weight with half life of several days. rHb 4.11 and rHb 4.14. They will follow rHb 1.1
in clinical studies.
(2) About toxicities, I have studied the data on trial with rHb 1.1 so far and toxicities are clinically insignificant. Since the rHb 1.1 is purified from E. Coli fermentation tanks, there has been minor incidences of reaction, probably to foreign proteins. In phase 2 studies, this issue was taken care of by giving Terbutaline to all patients before they received rHb 1.1 solution. Terbutaline is sympatho mimetic compund like Epinephrine and reduces-eliminates allergic reactions. Such allergic reactions can occur with other products like famous anti cancer drug Taxol, derived originally from bark of Yew tree. All patients who receive Taxol, routinely receive Decadron, Benadryl and Cimetidine before being given Taxol, to prevent allergic reactions. So this should not be a significant problem. Also, by further refinement in the manufacturing process, chances of possible allergic reactions can be further reduced or eliminated.
(3) About costs, I am not an expert. But I do remember Chairman of Somatogen, disputing Mr. Kelly's assertion about costs. It is hard to believe that Mr. Kelly is great expert about manufacturing costs of rHb 1.1. I dont know what is the basis of his statement. It is hard to believe that he is more knowledgable about manufacturing process-cost of rHb 1.1 than Chairman of Somatogen.
I dont know if Mr. Kelly is biased or he has convinced himself negatively about about rHb 1.1 due to some strange logic. As a trained and board certified Hematologist, I can certainly say that his first two assertions are vastly exaggerated and clinically insignificant.
Thanks
(Bharat H. Barai M.D.) |
