Australian drug delivery technology firm, Acrux is developing and commercializing a range of patient-preferred pharmaceutical products for global markets using an innovative, patented technology to administer drugs through the skin.

In an interview with BioSpectrum, Mr Richard Treagus, Chief Executive Officer & MD of Acrux, explains how the company is leveraging the pharmaceutical market with its proprietary transdermal technology.

Acrux has a large portfolio of products in the clinical trial/ development stage. When will these products hit the market and in which countries would you be launching the products?
Acrux has the following products in clinical development:

• Estradiol MDTS (EvaMist in the USA) to treat menopause symptoms.
• Testosterone MDTS to treat decreased libido in women.
• Testosterone MD-Lotion to treat testosterone deficiency in men.
• Nestorone plus Ethinyl Estradiol MDTS contraceptive spray for women.
• Nestorone plus Estradiol MDTS contraceptive spray for women.
• Fentanyl MDTS to treat chronic pain.

It is anticipated that Evamist will be launched in the US in the first half of 2008, and Estradiol MDTS in Australia in 2009. Testosterone MD-Lotion is entering phase III clinical trials, and it is anticipated that this product will be on the market in the second half
of 2010.

Please elaborate on the innovative drug delivery technology that Acrux has developed.
Testosterone MD-Lotion utilizes the Acrux’s proprietary technology platform, which is a combination of the drug, a penetration enhancer and a volatile solvent. The formulation is composed of a fast-drying alcohol-based vehicle with the active drug and a skin penetration enhancer. The volatile component evaporates very quickly after spraying, and as a result the drug and penetration enhancer accumulate in the skin. This occurs rapidly and creates a depot of active drug in the skin, from which it is slowly absorbed into the bloodstream. A penetration enhancer is a compound that allows a drug to pass through the top layers of the skin. The inclusion of a penetration enhancer provides enhanced and sustained drug delivery. The enhancer used in this system has GRAS status (Generally Recognised As Safe), due to its long term and extensive use in humans.

How is Acrux’s transdermal technology different from other products?
The Acrux technology platform is formulated to be fast drying, quickly absorbed, non-irritating to the skin and invisible after application. As a result, the products utilising the platform are expected to avoid the localized irritation or inflammation typically associated with patches. Unlike tablets, it also delivers the drug to the bloodstream without passing through the digestive system, which may be more suitable to some patients in certain circumstances.

The product attributes for Testosterone MD-Lotion will deliver significant benefits for patients when compared to the existing testosterone gel products. This will provide a clear and unique selling proposition, which will primarily focus on the unique ‘no-touch’ method of application. This will avoid sticky or messy hands, and reduce the risk of cross contamination of the product via touching. The product is fast drying, has no lingering odour or tackiness, and has a total application time, including drying, less than leading gel. Another key attribute is that the armpit application is a discreet and convenient application site, which provides a vastly reduced risk of transfer. Feedback from market research and our trials has shown this procedure can be considered part of the normal grooming routine.

Acrux has entered into many partnerships and licensing deals. Can you elaborate on them?
Acrux licensed its lead product, Estradiol MDTS (branded EvaMist in the US) to Vivus at the end of phase II clinical trials. Vivus completed the phase III development of the product and submitted an NDA to the FDA in 2006. Following submission of the NDA, Vivus completed a sub-license agreement to KV Pharmaceuticals, which will market the product throughout the US. Under the original license deal with Vivus, Acrux retained rights to license Estradiol MDTS in Australia and New Zealand.

In June this year, Acrux announced that it completed a licence agreement with Aspen Pharmacare Australia, a subsidiary of the South Africa-based multinational pharmaceutical company. Aspen will market Acrux’s first product in Australia, Estradiol MDTS to treat menopause symptoms. Acrux expects to submit a marketing application to the Therapeutic Goods Administration (TGA) in the third quarter of 2007. Following approval, Aspen will be responsible for manufacturing, marketing and distribution in Australia and New Zealand. Aspen will pay Acrux a royalty on net sales, with the product expected to be available to Australian women in 2009.

In March, this year, Acrux through two separate deals  licensed worldwide rights to its technology for selected contraceptives and for an undisclosed proprietary drug to Organon, the human healthcare business unit of Akzo Nobel. Organon and Acrux will develop and commercialize contraceptives, delivered through the skin using Acrux’s unique spray technology. Under the first agreement, Organon has licensed Acrux’s technology for use with selected contraceptive compounds.

Acrux also has a licence, development and commercialization agreement with Elanco Animal Health, a division of the global pharmaceutical group, Eli Lilly and Company. Elanco has global, exclusive rights to exploit the Acrux technology in the field of companion animals. Under the Agreement, Elanco is developing a range of veterinary products for global markets, using Acrux’s unique liquid technology to deliver drugs across the skin of animals. Elanco’s lead product will enter pivotal phase III clinical trials in the USA and Europe in the second half of 2007 and several other drug candidates are currently under evaluation.

In addition to these major agreements, Acrux has licensed Testosterone MDTS to Vivus, and AUS/NZ distribution rights for Testosterone MDTS and Fentanyl MDTS to CSL Limited.

Globally what is the market size for transdermal products and how does Acrux plan to capitalize on this market?
According to Transdermal Drug Delivery – Technologies, Companies and Markets, A Jain PharmaBiotech Report (Nov 2006) the market size for existing transdermal drugs has been estimated in 2005 at $12.7 billion globally. Acrux is focused on exploiting its proprietary technology to capture market share in important sub segments of this market, and as such the existing pipeline is focused on large and growing markets, that represent good opportunities to capitalize on the growing transdermal market. Here is a summary of three markets that Acrux is currently targeting:

t  Ex-manufacturer sales of testosterone replacement therapies for men in 2006 in the USA alone were more than $500 million, growing at 14 percent per annum, to which the leading transdermal gel contributed $377 million. Sales in the key European markets of Germany, UK, France, Italy, Spain and Sweden are currently growing at 20 percent per annum. It is estimated that over 20 percent of the US male population over 50 suffer from testosterone deficiency, with the incidence increasing with age. Approximately 10 percent of hypogonadal men currently receive testosterone replacement therapy, and this is expected to grow with increasing patient and physician awareness.

t  In 2006, sales of all prescription estrogen products in the USA were approximately $1.5 billion, with the transdermal segment of the market approaching $300 million. Acrux’s licensee in the US, KV Pharmaceuticals, has a strong women’s health franchise and will leverage the promotion of EvaMist through its current branded sales force, focusing on the specific targets of OB/GYN and select Primary Care Physicians who write prescriptions for estrogen replacement therapy.

t  Worldwide sales of hormonal contraceptive products in 2006 were approximately $6.7 billion. The availability of a wide range of effective, safe and appealing contraceptive products is viewed as one of the most important issues in contraception. This enables women to choose the method most appropriate to their needs and lifestyle.