Necessity is the mother of invention, so the saying goes.
Sometimes it is also the father.
The father in this case is Dr. Tony Reid, previously the Primary Investigator (PI) on the first-in-human (FIH) clinical trial for nibrozetone (RRx-001) (see blog post entitled EpicentRx Word of the Week: Nibrozetone [RRx-001]) and now EpicentRx CEO. In that FIH trial, back in 2011, well before Tony joined EpicentRx, when he was the PI at University of California at San Diego (UCSD), close to 100% of nibrozetone-treated patients developed a very tough-to-tolerate infusion phlebitis (IP) even at the lowest doses administered. The definition of infusion phlebitis is pain in the vein, or, more precisely, acute inflammation of a vein into which a needle has been inserted for the delivery of medication, in this case nibrozetone (RRx-001). Signs and/or symptoms of IP include pain—one of Dr. Reid’s patients memorably compared the sensation of nibrozetone (RRx-001) infusion to “hot sauce in my arm” and another to “rocket fuel”, which is oh-so-apropos because nibrozetone derives from a component of rocket fuel—and superficial clotting or thrombosis. Superficial thrombosis carries the risk of progression to deep venous thromboembolism, which, in turn, is associated with decreased blood flow to the extremities and possible infection.
Here Dr. Reid, a medical MacGyver, who invented the much-used Reid Sleeve, a foam-based compression device for the treatment of chronic lymphedema that arises from blockage of the lymphatics, saw a problem in need of a solution. And so, as he is wont to do, Dr. Reid improvised or “MacGyvered” a method to make nibrozetone (RRx-001) more tolerable based on his in-depth understanding of the mechanism of action—coinfusion with a small sample of the patient’s own blood or autologous blood. This autologous blood-based method of delivery worked because it sequestered the main mediator or substance that was responsible for the infusion phlebitis.
And so, with the help of EpicentRx team members like Scott Caroen, was born the hermetically sealed, patent-protected device called the eLOOP—not necessarily out of thin air but out of thin tubing, which is still a form of magic. The “e” stands for both EpicentRx and erythrocyte or red cell, and the “LOOP” for the semi-circular tubing with a 3-way stopcock into which less than one tablespoon’s worth of the patient’s blood is collected, mixed with nibrozetone (RRx-001) and injected back through the veins over a timeframe of 10-15 minutes. The proprietary device is small, simple, easy-to-use, and portable, having been used at the bedside by literally hundreds of oncology nurses to deliver nibrozetone (RRx-001) to almost 300 patients across 75+ clinical sites in the United States and China. The eLOOP is also customizable for the delivery of several other hard-to-take therapies. More on that in a subsequent blog post.
Meanwhile, for more background on the eLOOP, if that’s something of interest, click on the following links to the published peer-reviewed manuscripts by EpicentRx authors Scott Caroen et al. entitled, Superficial Venous-Associated Inflammation from Direct IV Administration of RRx-001 in Rats and Rationale and necessity for delivery of RRx-001, a Myc and CD47 antagonist, by intravenous blood mix.