A small Australian company with big ideas in transdermal drug delivery.

Acrux has developed a revolutionary Metered Dose Transdermal System (MDTS) that enables transdermal delivery of small molecule drugs without the use of skin patches. The technology is based upon absorption enhancers used for over 20 years in sunscreens, which the company has applied to treatments that are currently in clinical testing, including estrogen, testosterone and a pain management compound.

“We’ve completed phase II clinical trials with Estradiol MDTS, which has low skin irritation and elegance as major advantages over patches,” said Igor Gonda, Acrux’ Chief Executive Officer and Managing Director.

The company is following an accelerated 505(b)2 registration path with the US Food and Drug Administration for Estradiol MDTS as a hormone replacement therapy for women. It is planning to start phase III trials this year and file an NDA (new drug application) in USA in 2004.

The product has a low probability of causing skin irritation due to its unique design. MDTS incorporates a small spray bottle that is placed directly against the skin, delivering a measured dose of active compound in conjunction with patented ACROSS absorption enhancers. These absorption enhancers enable active compounds such as estrogen to penetrate the skin and enter the circulatory system while avoiding first pass filtration by the liver. MDTS enables once a day application due to the steady rate of absorption of active ingredient into the blood stream, preventing spikes in serum concentration while lowering the risk of side effects.

The active transport mechanism, the ACROSS enhancer (octisalate) in a volatile solvent, “forms an invisible patch inside the skin that allows drugs to penetrate the stratum corneum and diffuse into lower parts of the skin and into the blood stream,” Gonda said. Octisalate is of known safety, and is used in sunscreens at doses many times higher than Acrux uses. Gonda said that MDTS has shown no skin irritation in clinical trials, and has greater convenience than traditional patches. “The preferred configuration is daily application. With MDTS you take a shower in the morning, spray on, and you’re done,” Gonda said.

Acrux’ business strategy involves taking off-patent or soon to be off-patent drugs and developing them for transdermal delivery. “We operate by starting with drugs that are, or will be off-patent in five to six years so that development will be completed by the date the original patent expires,” Gonda said. Suitable compounds for transdermal delivery are small molecules less than 800 daltons molecular weight. Gonda also said that the company uses in-silico modeling, an examination of clinical and regulatory hurdles, a quantitative risk assessment model and net present value assessment when considering new projects. When the company starts with a drug that is available on the market with no intellectual property barriers, it develops the MDTS variation as far as possible in-house in order to maximize value at the stage of out-licensing. Acrux uses contract research organizations to handle early and intermediate clinical development.

Acrux originally attained a global license for the ACROSS enhancers from Monash University in Melbourne, Australia. “Actually, the technology was first identified by three Australian scientists – Barrie Finnin, Barry Reed and Timothy Morgan - working at the Victorian College of Pharmacy which is now a part of Monash University in Melbourne, Australia,” Gonda said. These three scientists, together with Bill Charman and Ross Dobinson, established Acrux based upon the discovery of certain safe sunscreens acting as potential drug delivery vehicles. The company received Series A funding of AUS$5 million in 1999 as well as AUS$3.8 million in the form of a start grant from the Australian government. Acrux has since received AUS$ 11.5 million in second round financing (primarily from Deutsche Bank and Singapore-based Blue Dot Capital), and in June 2002 AUS $10 million in third round financing from the Queensland Investment Corporation.

Acrux has entered into collaborations with major pharmaceutical companies including Pharmacia, with which it partnered in March 2002 for the development of transdermal applications for Pharmacia compounds. The company is also working in conjunction with NASDAQ-listed Connetics in the development of local anesthetics and anti-psoriatics, and with another company in the development of cosmeceutical products to combat skin aging. “One of our key advantages in the cosmeceutics area is that active ingredients are delivered in a persistent manner, with more specific delivery to the target skin layer,” Gonda said.

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