PolyMedix Completes Successful Phase 1B Clinical Study Of Heparin Antagonist PMX-60056

Main Category: Blood / Hematology
Also Included In: Clinical Trials / Drug Trials
Article Date: 29 Oct 2009 - 0:00 PDT

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PolyMedix, Inc. (OTC BB: PYMX), an emerging biotechnology company developing new therapeutic drug products to treat infectious diseases and acute cardiovascular disorders, has completed a second successful clinical study of its anticoagulant reversing agent, PMX-60056. The Phase 1B clinical study was a pilot proof-of-concept study conducted in the U.S. under an Investigational New Drug application (IND) filed with the U.S. Food and Drug Administration (FDA).

Highlights from the Phase 1B clinical study include:

- PMX-60056 completely reversed the anticoagulant effects of heparin and normalized blood clotting time in human subjects in less than 10 minutes.

- No serious adverse events occurred during the study of PMX-60056.

"We are very proud and happy to have completed this major step in the development of PMX-60056," commented Nicholas Landekic, President & Chief Executive Officer of PolyMedix. "PMX-60056 represents a new class of drug, which we call heptagonists, and we believe is the only compound being developed as a reversing agent for heparin and low molecular weight heparins (LMWHs). PMX-60056 may offer important benefits and improvements in treating the potential bleeding complications of heparin, which was targeted in this study, as well as LMWHs which we hope to investigate in future clinical studies. We hope that in the future PMX-60056 will allow physicians to continue to use heparin, the only anticoagulant currently available for open-heart surgery and kidney dialysis, with a new and unique reversing agent, and potentially the first reversing agent for LMWH's."

"I am encouraged by the promising results with PMX-60056. This drug could be an important addition to the medical armamentarium, and may address unmet clinical needs in reversing heparin as well as being potentially the first reversal agent for LMWH," commented Dr. Mark Stafford-Smith, of Duke University Medical Center, a clinical advisor to PolyMedix.

This Phase 1B clinical study evaluated subjects who received heparin followed by PMX-60056 or placebo. Significant additional clinical studies and regulatory submissions, and regulatory approvals from the FDA and other regulatory bodies, will be required before PMX-60056 could be commercially sold as a reversing agent for heparin or for LMWHs. PolyMedix is currently evaluating plans for the continued clinical development of PMX-60056. There can be no assurances that future clinical studies will be successful, that required regulatory approvals will be obtained, or that the company will be able to market and sell any products based on PMX-60056.

Mr. Landekic went on to comment: "This study represents a validation of the capabilities and efficiency of PolyMedix's structure-based drug design approach. In developing PMX-60056, we went from the very beginning of drug design to attaining a clinical efficacy endpoint while spending less than $10 million in direct costs. We attribute this efficiency realized in developing PMX-60056 to our structure-based drug design approach, and the skill of our seasoned research and development leadership."

Study Design

The pilot proof-of-concept study was conducted using a double-blind, placebo-controlled, crossover design, with six healthy human volunteer subjects. This study design and low number of subjects were intended to generate meaningful results for a pilot study at minimal cost. Twenty minutes after administration of a 70 U/kg dose of heparin, which is sufficient to produce anticoagulant activity, each of the subjects was administered, in a blinded manner, either a single dose of 0.3 mg/kg of PMX-60056 or a placebo as a 10-minute intravenous infusion. With the crossover design, each subject was dosed twice, initially with heparin and either PMX-60056 or a placebo and then, two days after the first dose, with heparin and whichever (PMX-60056 or a placebo) he did not receive in the first dose. Each subject thus acted as his own control.

The primary endpoint of the clinical study was safety, specifically whether blood pressure decreases would be mitigated by the presence of heparin, and the secondary endpoint was efficacy, as measured by blood clotting time. The desired outcomes were no clinically significant decrease in blood pressure, and rapid reversal of activated clotting time (ACT), a standard bedside blood clotting measurement, and activated partial thromboplastin time (aPTT), a more accurate laboratory measurement of blood clotting time. These blood clotting times are machine-read to ensure objective measurement.

PMX-60056 Background

Heparin and LMWH are widely used anticoagulant drugs to prevent blood clotting, the use of which has a risk of potentially serious bleeding side effects. There is currently no alternative to heparin for open-heart surgery and kidney dialysis. Protamine, the only drug approved to reverse the action of heparin, is associated with serious potential side effects, and can lead to late-onset bleeding as it disassociates from heparin. There is no approved reversing agent for LMWH. Therefore, we believe there is a substantial medical need, as well as significant market potential, for a viable alternative to protamine and a LMWH reversing agent. Preclinical studies conducted by PolyMedix and its collaborators have suggested that potential advantages of PMX-60056 over protamine may include reduced bleeding complications, reduced risk of allergic reactions, and the ability to neutralize LMWH.

PMX-60056 was designed to bind to the pentasaccharide region found on heparin and LMWH. PMX-60056 is believed to bind to heparin and LMWH through electrostatic and other interactions, to block the action of heparin and LMWH. This molecular combination is believed to persist until removed from circulation by normal processes. In previous studies conducted by PolyMedix and its collaborators, PMX-60056 has been demonstrated to reverse the action of heparin in human plasma, in isolated human whole blood, and in animal studies in rats and dogs.

Safety

No serious adverse events (SAEs) occurred during this Phase 1B clinical study of PMX-60056. No clinically significant blood pressure effects were observed in this study in the presence of heparin. There were several non-serious reports of "warmth" and/or "itching" during and shortly after the infusions, but no such effects were reported significantly beyond the 10-minute infusion time.

Efficacy

In all subjects receiving PMX-60056, there was a rapid and complete reversal of the anticoagulant action of heparin, as measured by ACT and aPTT. Each subject's minimum ACT and aPTT readings after being dosed with PMX-60056 were at or below the subject's ACT and aPTT readings prior to being dosed with heparin. The heparin reversal appeared to occur at or before the end of the 10-minute infusion of PMX-60056, suggesting that the 0.3 mg/kg dose may have been in excess of requirements for 70U/kg heparin. Furthermore, although not shown in the graph below, the reversal was permanent: there was no return of anticoagulation during the hours required for heparin's effects to decline naturally.

PolyMedix plans to host a conference call to discuss these Phase 1B results in the near future. We plan to announce the date and time of the event shortly.

Source
PolyMedix, Inc.