Ampio Pharmaceuticals Inc., a biopharmaceutical company conducting clinical trials on its three lead drugs (Ampion, Optina and Zertane), licensing distribution of these drugs and developing additional new drugs, has received notice of allowance of a patent from the US office of patents and trademarks for its DME drug Optina. Ampio also received a notice of allowance of a similar patent from the Canadian Intellectual Property Office.

These initial patents cover the North American territories and multiple additional patents for using Optina for the treatment of macular edema and diabetic retinopathy are pending worldwide.

According to Michael Macaluso, Ampio's CEO, “Optina is an ultra-low oral (capsule), not commercially available, dose of danazol for the treatment of DME. To our knowledge, no other oral drug to treat this condition exists and there is currently no drug approved by the FDA for this condition. The allowance of these patents in North America is an important step in the development and commercialization of this novel drug as they include multiple claims for the beneficial effects of ultra-low dose Optina™ on vascular hyperpermeability encountered in DME and other vascular leakage syndromes. These patents have an unusually long patent life that expires in 2030. In contrast, most drugs at this stage of development (just before a pivotal trial) have exhausted a large portion of their patent life. These patent claims provide especially strong protection because of the unexpected finding of efficacy only at the very low doses. Ampio is currently in discussions with potential partners to co-develop Optina for DME.”

Dr David Bar-Or, chief scientific officer for Ampio, explained, “The mode of action of Optina involves the remodeling of the actin cytoskeleton (F-actin) of endothelial cells (cells that line the inside of blood vessels, including the retinal blood vessels) so that the adhesion molecules between these cells are tightly bound to the peripheral actin (cortical) resulting in tighter junctions among these cells, hence preventing vascular leakage from the blood compartment into tissue. The basic mechanism of action of Optina is described in a recently published manuscript entitled: "Biphasic effect of danazol on human vascular endothelial cell permeability and f-actin cytoskeleton dynamics" in Biochemical Biophysical Research Communications (BBRC 21 April 2012 http://dx.doi.org/10.1016/j.bbrc.2012.04.066). This is the first in a series of publications describing the biphasic effect of danazol on vascular permeability which is beneficial in reducing permeability (nano molar concentrations) and increasing permeability at the higher concentrations used in other approved indications (micro molar).”

Dr Vaughan Clift, Ampio's Chief Regulatory Officer, noted, “A clinical study of Optina for DME conducted in a double masked, placebo controlled manner at Saint Michael Hospital in Toronto, Canada, confirmed the in vitro findings that the ultra-low dose of danazol is beneficial while the high dose is detrimental. Complete analysis of the Optina™ trial is underway by our CRO and results will be published in the proper venues following a pre-IND meeting with the FDA. Ampio is preparing for a pre-IND meeting with the FDA to discuss plans for a pivotal trial(s) in the US under the 505(b)2 registration.”

Diabetic retinopathy is damage to the retina of the eyes caused by complications of diabetes mellitus and often resulting in loss of visual acuity and blindness. Macular edema of the eyes is often an early form of diabetic retinopathy that causes significant vision loss. Almost all Type 1 diabetics and more than 60 per cent of Type 2 diabetics will develop retinopathy. There is no effective daily drug treatment for diabetic retinopathy other than general measures, such as controlling blood sugar, hypertension, blood lipids, etc. Due to the global diabetes epidemic, diabetic retinopathy is recognized as a high, unmet medical need that would benefit from having oral therapeutic options available. The only treatments available for macular edema now are laser therapy, injection or implantation of drugs into or around the eyeball (not approved in the US or Canada). To our knowledge, Optina is the only proposed oral treatment for this condition.

Optina is an orally administered ultra low dose of danazol, for the treatment of diabetic macular edema (DME). Ampio's Chief Scientific Officer discovered an unexpected activity in his investigation of the mechanism of action of danazol: very low doses reversed inflammation-induced increases in the permeability of blood vessels, thus reducing vascular leakage. Dr Bar-Or subsequently managed in-vitro studies that suggested this effect may reduce the vasogenic edema produced by various vascular leak syndromes, including diabetic macular edema (DME) which can impair vision and cause blindness. The specific Optina dosages used in the trial are proprietary and subject to multiple patent filings.

Danazol, a derivative of the synthetic steroid ethisterone, was approved by the FDA in the 1970s for endometriosis and, more recently, for other chronic indications, including hereditary angioedema, ITP and fibrocystic disease of the breast.

Ampio Pharmaceuticals, Inc. develops innovative proprietary drugs for inflammation, eye disease, kidney disease, CNS disease, metabolic disease and male sexual dysfunction.