Shares of Ampio Pharmaceuticals Inc. soared Monday after the biopharmaceutical company reported positive data from its interim review of the first 50 percent of patients enrolled in a Phase II study of Optina in diabetic macular edema (DME).

The trial, conducted at St. Michael Hospital in Toronto, was designed to study the safety and efficacy of twice-daily oral doses of Optina, an orally administered ultra-low dose of danazol, to reduce macular edema as determined by optical coherence tomography (OCT), a measure of the thickness of the macula.

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, immune thrombocytopenia and fibrocystic disease of the breast.

A preliminary assessment of OCT in the study indicated a beneficial and consistent effect with an ultra-low dose of Optina at four weeks and 12 weeks of treatment, with no apparent benefit at a high dose, according to Vaughan Clift, an endocrinologist and Ampio's chief regulatory affairs officer.

The preliminary results mirrored the company's in vitro data, which demonstrated a biphasic effect for the drug – effectiveness in reducing vascular permeability at very low doses and cessation of the beneficial effects at higher doses, which are used clinically for other approved indications.

Based on the beneficial results of the ultra-low doses of the compound and the potential lack of efficacy at the higher doses, Ampio plans to end the study ahead of schedule and begin preparing a consultation package for the FDA that includes basic scientific data and clinical findings, according to Clift.

The next step for the Greenwood Village, Colo.-based company is to seek a meeting with the FDA to discuss the design of a pivotal trial in the U.S. under a 505(b)(2) filing, likely during the third quarter.

The company plans to provide a detailed review of the Phase II results after its contract research organization completes the data analysis, he added.

The application of ultra-low doses of danazol in DME was discovered serendipitously by David Bar-Or, Ampio's chief scientific officer and a molecular biologist, who serves as director of trauma research at Denver's Swedish Medical Center and St. Anthony Central Hospital. Bar-Or and Ampio CEO Michael Macaluso, a serial entrepreneur, co-founded DMI BioSciences Inc. in 1990, with Bar-Or gaining the rights to his discoveries at the hospital in return for the publications he generated on the hospital's behalf.

Over the years, those discoveries mushroomed into more than 300 compounds, but most were new chemical entities. Danazol was one of three discoveries with strong patent positions that fell into the repurposed drug development category, which allows for smaller trials and a more straightforward regulatory filing, leading to a shorter commercialization timeline.

Bar-Or was investigating danazol's mechanism of action when he discovered that very low doses reversed inflammation and induced increases in the permeability of blood vessels, reducing vascular leakage. The actual dosages of Optina used in the Phase II trial are proprietary and subject to multiple patent filings, according to Clift, who said conventional uses of the drug range from 200 mg to 800 mg per day.

Although Bar-Or was studying the anti-angiogenic properties of danazol in endometriosis, he realized that, at one-tenth the dose that is commonly used for other conditions, danazol actually "turned off" vascular permeability.

"That makes it very valuable for a whole series of vascular permeability diseases, and one of the classic examples is diabetic macular edema," Clift said.

Danazol has years of patient experience, he pointed out, with side effects that are "very benign – even at higher doses."

Repositioning the drug gives Ampio strong patent protection for Optina, since danazol has no approved indications below a 100-mg dosage.

Should it successfully develop an oral treatment for DME, Ampio could make a quantum leap over competitors. With the incidence of diabetes reaching epidemic proportions around the globe, pharmas are eager to manage precursors such as DME and resulting complications, such as diabetic retinopathy. Nearly all Type I diabetics and more than 60 percent of those with Type II diabetes develop retinopathy, according to Clift.

Most biotechs seeking to develop more effective treatments for DME have focused on improving injectable drugs. For example, pSivida Corp., of Watertown, Mass., and partner Alimera Sciences Inc., of Atlanta, are developing Iluvien (fluocinolone acetonide intravitreal insert) via the European decentralized procedure for vision impairment associated with chronic DME considered insufficiently responsive to other therapies.

In November 2011, the companies received a second complete response letter from the FDA for Iluvien. (See BioWorld Today, Nov. 14, 2011.)

And Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., and Bayer HealthCare are partnered on VEGF Trap-Eye (afilbercept ophthalmic solution), which is in Phase III trials for the DME indication. (See BioWorld Today, April 11, 2011.)

"To our knowledge, Optina is the only proposed oral treatment for this condition," Clift said.

Ampio's stock had been trading near the bottom of its 52-week range, closing Friday at $2.68. On Monday, shares (NASDAQ:AMPE) opened at $3.29 and reached $4.58 before settling back to close at $3.82, a gain of 42.5 percent.

The company reported operating expenses of $2.8 million for the quarter ending Sept. 30, 2011, with no debt and $7 million cash on hand.

Clift said the company would seek to partner the drug with a pharma, either before or following the Phase III – which only needs to be sufficiently long to demonstrate efficacy.

"It may be a very short trial," he said. "We can't make any claim of long-term benefits – only short-term benefits – so we don't need to do a two- or three-year study."