Medical Device Daily and JENNIFER BOGGS, Medical Device Daily

Delivering drugs through the skin usually means with a patch. But patches have a variety of disadvantages, not the least of them being a certain level of inefficiency and, for some users, irritated skin.

Coming up over the technology horizon are new systems for drug delivery through the skin, chiefly sprays and gels, that avoid these and other downsides.

One such developmental company using a spray-on transdermal technology that it terms a “patchless patch” is Acrux (Melbourne, Australia), for delivery of Nestorone, a contraceptive drug.

Acrux acquired the worldwide license to intellectual property from the Population Council (New York) for the use of Nestorone with its patented metered-dose skin spray delivery (MDTS). It said it would commercialize Nestorone MDTS while also sublicensing it to partners.

In addition, Acrux said it or its sub-licensees will make Nestorone MDTS available at reduced prices to public-sector groups providing human reproductive health products to disadvantaged people.

The delivery system looks like an inhaler with an inverted cone at the top. The flared portion of the cone is placed against the skin of the forearm and the user then presses an actuator to spray the drug onto the skin in a daily regimen.

Igor Gonda, CEO of Acrux, told Medical Device Daily that the spray is fast-drying and quickly disappears, with the drug absorbed into what he describes as the “brick and mortar” structure below the surface of the skin. He said it essentially then accumulates in the “mortar” spaces and then travels into the bloodstream on a sustained basis over 24 hours.

Results of a Phase I clinical trial, under a development agreement with the Population Council, showed that a once-daily application provides the level of Nestorone in the blood known to be effective for contraception. A Phase II trial, to start in the second half of 2006, aims to demonstrate that Nestorone MDTS controls ovulation. Acrux said it would seek partners for the remaining steps in global commercialization.

The sprayed drug is “a very attractive new option for contraception,” Gonda said. “It combines our unique technology with the know-how of one of the world’s leading drug companies.”

Besides being “more discreet and less irritating” than a patch, Nestorone MDTS, he said, “will prove to have a better safety profile than other hormonal contraceptives. Market research has shown that many women will prefer the ease and convenience of this method” over pills, injections or patches.

Gonda noted that Acrux sees a large opportunity for Nestorone MDTS, given annual worldwide sales of hormonal contraceptives of more than $4 billion, and sales of transdermal contraceptive patches in the U.S. of more than $400 million a year.

Peter Donaldson, CEO of the Population Counsel, said he was pleased with the progress Acrux has made in its developmental efforts. “An important part of our mission is to meet the need for reproductive healthcare products on a global scale, and we believe that Acrux’s technology can be an attractive option for many women around the world.”

In addition to Nestorone MDTS, Acrux has two other products, delivered as daily sprays, closer to commercialization: Evamist for menopausal symptoms, in Phase III trials, and testosterone MDTS, for decreased libido in women, just through Phase II.

Acrux has licensed U.S. rights for Evamist (Estradiol MDTS) and Testosterone MDTS to VIVUS and Australia/ New Zealand distribution rights for Testosterone MDTS and Fentanyl UDTS to CSL Ltd .

Using either the spray or “gel” approach for delivering drugs through the skin is IDEA (Munich, Germany), which has developed what it calls transfersome technology that uses “nanocapsules” containing small amounts of active drug that are then placed in a water-based gel or sprayable liquid.

The gel is applied to the skin, and as the water from the gel evaporates, the special chemistry of the nanocapsule travels into the skin’s micropores seeking water, pulling a drug, protein or some other large molecule along with it.

IDEA has just licensed the system to the global private equity firm Celtic Pharmaceutical Holdings (Bermuda), along with clinical and preclinical products in pain and inflammation, dermatitis and psoriasis. The deal calls for Celtic Pharma’s subsidiary, TDT , to acquire worldwide rights to these products, with TDT making an undisclosed up-front payment to IDEA, in addition to royalties.

TDT also agreed to invest at least $17.85 million for further work with the Transfersome-based portfolio.

“I don’t think it’s an exaggeration to describe this [technology] as a paradigm shift in drug delivery,” said Stephen Evans-Freke, co-founder and managing partner of Celtic.

IDEA intends to develop that product on its own and is completing Phase III trials in osteoarthritis in Europe.

All products in development are comprised of existing drugs designed with a Transfersome carrier to locally administer treatments through the skin.

“The chemistry of the Transfersome,” Evans-Freke said, “can control whether the capsules release their drug just under the surface of the skin, or go down to microvasculature just beneath the skin, or carry on through both those levels down to the deep tissue before they release the drug.” This delivery also results in “very high concentrations of the drug delivered to the site, without any of the drug getting into the circulatory system,” bypassing systemic side effects.

Clinical and preclinical compounds licensed from IDEA include products for treating skin pain and inflammation, CS dermatitis and psoriasis, onychomycosis and neuropathic pain. TDT also will evaluate other drugs using the system for other indications.

Celtic’s interest in the technology started with a 21% stake in IDEA in September.

“Normally, we won’t take a minority stake in a company,” Evans-Freke told MDD’s sister publication, BioWorld Today, “but in this case it was part of a broader strategy.”

Operating a bit differently from other private equity firms, Celtic focuses on acquiring and investing in late-stage programs, advancing those programs through regulatory approval and then selling product rights to pharmaceutical companies to commercialize.

“We’ll buy companies when we have to,” Evans-Freke said – referring to last year’s acquisition of Xenova Group (Slough, England) – “mainly because we wanted its drug-addiction vaccines.”

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