PolyMedix, Inc (OTC BB: PMYX), an emerging biotechnology company focused on developing new therapeutic drugs to treat life-threatening infectious diseases and acute cardiovascular disorders, announced that data from two Phase 1B/2 clinical studies with PMX-60056 were presented today, in oral and poster sessions, at the Annual American Heart Association Scientific Sessions Meeting. PMX-60056 is a synthetic, small-molecule designed to reverse the anti-clotting effects of both heparin and low molecule weight heparin (LMWH).
“Heparin-Antagonist PMX-60056 Rapidly and Completely Reverses Heparin Anticoagulation in Man”
"We are encouraged by the fast, permanent and complete reversal of the anti-clotting effects of heparin and low molecular weight heparin demonstrated by PMX-60056 in these studies," commented Dr. Eric McAllister, Vice President of Clinical Development and Chief Medical Officer at PolyMedix. "PMX-60056 restored blood clotting times to the normal range even before administration of the ten-minute infusion was completed. We look forward to continuing the development of PMX-60056 and advancing into a phase 2 clinical study."
Heparin Reversal Clinical Results
In an oral presentation, "Heparin-Antagonist PMX-60056 Rapidly and Completely Reverses Heparin Anticoagulation in Man," Dr. Eric McAllister reported on results from a Phase 1B/2 double-blind, placebo-controlled crossover clinical trial in six healthy male subjects. On two occasions separated by a 2-day washout period, each of the six subjects received a prophylactic dose of unfractionated heparin as an intravenous bolus, followed 20 minutes later with either PMX-60056 or placebo as a ten-minute intravenous infusion. Coagulation was assessed by two standard measurements of blood clotting time, activated clotting time (ACT) and activated partial thromboplastin time (aPTT).
All (6 of 6) subjects receiving PMX-60056 demonstrated rapid and permanent reversal of the anticoagulation effects of heparin, while none (0 of 6) demonstrated reversal after receiving placebo. The reversal seen in subjects receiving PMX-60056 was complete before the end of the infusion period, which suggests that less than the 0.3 mg/kg dose used may be required to neutralize 70 U/kg of heparin. The restoration of blood clotting seen with administration of PMX-60056 was permanent. For subjects receiving placebo, heparin was eliminated over a 4-hour period, as expected from known pharmacokinetics.
Low Molecular Weight Heparin Reversal Clinical Results
The poster presentation, "Heparin Antagonist PMX-60056 Rapidly Reverses Anti-Xa and aPTT Effects of Tinzaparin in Man" reported on a Phase 1B/2 double-blind, placebo-controlled crossover clinical trial in six healthy male subjects. On two occasions separated by a 2-day washout period, each of the subjects were given a subcutaneous injection of the standard prophylactic dose (175 IU/kg) of the LMWH, tinzaparin. Five hours later, which was the time of the expected maximum anticoagulation, each subject received either 0.3 mg/kg PMX-60056 or placebo as a 10-minute intravenous infusion. Three hours later, the same dose of drug was infused again to neutralize the additional tinzaparin still entering the blood stream from the subcutaneous delivery site.
The results showed that PMX-60056 rapidly reversed prophylactic doses of tinzaparin, demonstrating both reversal of anti-Xa activity and normalization of blood clotting times (measured using both ACT and aPTT). The effect was complete before the end of each ten-minute infusion period.
The degree of reversal was relatively constant at 0.4 anti-Xa units/mL, even though the peak anti-Xa effect of tinzaparin ranged from 0.4 to 1.0 IU/mL in subjects. Despite the resumption of anticoagulation from continued delivery of tinzaparin from the depot administration, PMX-60056 reversed the aPTT to normal by the end of each of the two infusion periods. The study also found mean systolic/diastolic blood-pressure reductions of 21/17 mmHg. These small reductions in blood pressure were almost certainly due to excess PMX-60056 remaining after all available tinzaparin had been matched. No important side effects were observed in the study.
There is no FDA approved reversing agent for LMWHs. PMX-60056 may allow the expanded use of LMWH in thrombogenic medical or surgical procedures that require rapid reversal of anticoagulation afterward, as well as for treatment of bleeding in patients taking long-term LMWHs.
"We believe PMX-60056 offers the potential to advance the management of coagulation in the use of heparin and low molecular weight heparins, both in routine surgical procedures and in cases of bleeding complications," commented Nicholas Landekic, President and CEO of PolyMedix. "Our clinical results may have shown for the first time, an agent's ability to fully normalize blood clotting time after the administration of a low molecular weight heparin. These data represent significant milestones for PolyMedix, and further validation of our rational drug design platform."
FDA announces recall of heart pumps linked to deaths and injuries