Peer Review PGE1 | NanoProstin Group

Marcus Gitterle, MD - Scientific Peer Review

PGE1 is a well-characterized biomolecule with powerful vasoactive, and inflammation-modulating characteristics, for which multiple therapeutic uses have been proposed, and for which there are at least two, FDA-approved indications.

PGE1, under the trade name Alprostadil is utilized to treat a number of congenital heart abnormalities, in the neonatal population. Given by continuous infusion via a standard IV pump into a central or peripheral IV, it has allowed many neonates to survive severe heart defects while waiting for a donor heart.

It is also used to treat Erectile Dysfunction, for which use it is administered via self-injection into the penile corpus cavernosum, where its vasogenic properties produce a rapid erection, allowing sexual function in men who might otherwise not be able to produce and sustain an erection, successfully.

The limiting factor in actualizing other uses for PGE1 is largely a function of its short elimination half-life, and the requirement for intravenous administration for most of these use cases.

Data exists showing significant efficacy with intravenous slow infusion of PGE1 in patients with severe peripheral arterial disease (PAD). This is a disease category with essentially no effective, FDA-approved non-mechanical, or surgical treatments. While PAD is a chronic, systemic disease, it is often treated surgically, or via catheter-based "endovascular” interventions at this time, even though such treatments do not fundamentally address the systemic nature of the disease process, and even though such treatments have shown limited, highly variable levels of efficacy, with many such interventions being the equivalent of a clinical “Hail Mary Pass.”

Systemic treatments for PAD that address any of the following needs would be highly desirable, and if proven efficacious would likely receive FDA approval and ready acceptance by clinicians:

Symptoms of PAD, such as claudication (extremity pain due to poor blood flow and lack of oxygen delivery) or pain at rest (a hallmark of severe PAD known as “Rest Pain”)
Arterial or diabetic ulcerations whose non-healing status is largely related to insufficient blood flow
The need for a “temporizing measure,” which prevents amputation while surgical or other options are being evaluated, or while a patient’s surgical fitness is being improved.

The current project proposes to enable additional use cases using alternative delivery methods; most specifically, a transdermal patch, which allows for slow elution of the active over a sustained interval.

What is compelling about the potential for a PGE1 Transdermal product is that it has the potential to provide each of the above-listed benefits, and because there is a venerable history of prior applications, the underlying mechanism is well understood by physicians, likely speeding acceptance of the new indication, and rapid adoption.

What is also compelling is that a significant percentage of PAD patients have no surgical or endovascular options, whether due to the anatomic nature of their disease or due to the fact that their health status renders them unfit to undergo surgery. For such patients, long-term management of their PAD with a PGE1 transdermal product might enable such patients to avert amputation,

find relief from ischemic pain, achieve healing of otherwise non-healing extremity ulcerations, and avoid the sharply curtailed life expectancy associated with amputation.

In addition, I believe that such a product might find application in diabetic ulcer healing. Diabetic Foot Ulcer (DFU) is an expensive, very common complication of diabetes mellitus types 1 and 2. Of the current Type 2 DM population of 30,000,000, approximately 5 million are expected to develop a DFU over their treatment lifetime. On average, these cost approximately 30,000 to treat.

The most severe DFU cases — Wagner Grade III, IV, and V — cost considerably more to treat, and a majority of these cases are associated with at least some degree of peripheral arterial disease. They are often treatment-resistant, and often require a resort to “Advanced Modalities” such as Hyperbaric Oxygen Therapy, and Engineered Dermal Substitutes, which leads to substantially higher costs, yet limited efficacy, and relatively poor and unpredictable outcomes, in spite of the increased costs. Third-party payers have a keen interest in reducing the over-utilization of these “Advanced Modalities,” and with good reason, given their extreme expense, and unclear value proposition.

I believe that it is likely that a transdermal PGE1 product could serve as relatively standard adjunctive therapy in the treatment of DFU, at substantially lower overall treatment cost than currently available “Advanced Modalities,” and that such a treatment could be applied to patients who might otherwise lack access to the specialized facilities required to deliver HBOT and Engineered Skin

Substitutes. Such a product could be simply prescribed by the attending physician, and the patient followed and treated normally, in other respects, with attention to standard wound care, elimination of pressure on the wound, infection control, diabetes management, and nutritional optimization.

Other indications are suggested by the abundance of data available on PGE1 related to modulation of inflammation, indicating that such a product might be ripe for the establishment of additional indications in the area of sepsis, chronic inflammatory diseases, and Adult Respiratory Distress Syndrome, including the acute respiratory syndromes associated with COVID-19 and related diseases.

I feel that an effort to develop a PGE1 product/product family is likely to meet with success in the areas discussed and that existing clinical and basic science data will expedite FDA approval of the new delivery vehicle, and additional indications.