Many said it couldn't be done, but Australian pharma firm Phosphagenics has developed what it claims is the world's first transdermal insulin formulation and has received the first signs that the product may have blockbuster potential.
The company, which focuses on drug delivery and drug enhancement, has reported the first positive results from preclinical trials using its novel transdermal insulin (TMP-02/insulin) formulation on pigs.
"The study has successfully demonstrated the ability of TMP-02/insulin to deliver insulin across the skin of pigs at levels sufficient to lower glucose in the blood," said the independent principal investigator of the study, Professor Frank Dunshea, Department of Primary Industries, Victoria, Australia.
"These results are impressive, as the non-diabetic pig model is considered to be robust for both testing the penetration of drugs across skin as well as for determining the efficacy of diabetes therapies."
New ways of delivering drugs that contain large molecules, such as proteins, are highly sought after because these drugs are the hardest to deliver successfully, and often require subcutaneous delivery by injection - insulin is a prime example.
As a result of the challenges of getting large compounds into the body effectively, production of these drugs is often also complex and expensive.
Phosphagenics is one of a growing number of new contenders vying to cash in on the non-injectable insulin field, competing with pharma giants such as Pfizer who have recently launched the first inhalable form of insulin, however, the firm believes it has developed a drug delivery technology that is unique, being able to deliver large-size insulin molecules through the skin's surface, without the need for burdensome and expensive drug delivery devices.
"We can deliver a molecule up to 40,000 daltons in size and as far as I'm aware, no other company that has developed the technology to deliver large peptides and proteins through the skin, at least without causing a huge abrasion," Michael Preston, Director of Phosphagenics told In-PharmaTechnologist.com.
"It may be applied as a cream but it will most likely be a patch for dosing reasons. We are still working on administration of the drug and release times at this stage."
Phosphagenics has discovered that a phosphorylated form of vitamin E (tocopheryl phosphate) could be used to penetrate the skin nine times greater than regular vitamin E.
"With this in mind, we developed a novel drug delivery platform that can deliver a multiplicity of drugs safely and conveniently through the skin, turning poorly bioavailable drugs into significantly bioavailable drugs," said Preston.
The patented technology uses microencapsulation, which involves capturing the drug molecules with a thin layer of phosphorylated vitamin E to create a nanosphere.
This nanosphere then acts as a carrier that uses existing natural transport mechanisms to "carry" drugs across the skin without disrupting the skin's surface.
Existing transdermal technologies rely either on passive diffusion across skin membranes - a method which requires improving drug penetration with solvents, enhancers or lasers that modify the properties of the outermost layers of the skin; or by using electrical or thermal technologies to "push" drugs through the skin.
"We have an infinite array of drugs we know we can deliver with this technology such as hormones and antipsychotic drug," said Preston.
The company has developed two formulations of the carrier - TPM-01 or TPM-02. TPM-01 delivers small molecule drugs (e.g. morphine, fentanyl, oxycodone, atropine, estradiol, testosterone) and TPM-02 delivers both small and large molecule drugs (e.g. insulin, PTH, proteins).
Both formulations of the carrier have anti-inflammatory and anti-erythema properties, which minimise skin irritation and can provide sustained transdermal delivery of drugs, said Preston.
"We can also vary the size of the nanosphere according to the desired drug penetration. If we want to stop a drug penetrating through the skin we make large nanospheres, if we want the drug to go deep into the body we make them smaller," he said.
The technology has been classed as a "penetration enhancer" by the US Food and Drug Administration (FDA) so the company has effectively been given the green light for a fast-tracked regulatory route.
Phosphagenics can use the new technology not only to enhance transdermal delivery but also to enhance all types of drug delivery including oral, nasal and inhaled, but has chosen to initially focus on transdermal delivery, said Preston.
"This is because we are only a small biotech company and the road to market for transdermal treatments is much quicker."
"When we have the capacity to explore other forms of delivery we have the technology just sitting there, waiting to be used," he said.
The company now has a total of five transdermal drugs using this technology in the preclinical stage and a more advanced transdermal morphine product now in Phase II trials.
Phosphagenics will begin Phase I clinical trials on its insulin drug in July that will look at efficacy, safety and tolerability of the drug in humans and is expecting ethics committee approval any day now.
"I will be very surprised if we don't have the results published by September," said Preston.
"Initial studies will involve patients with Type 2 diabetes but we are eventually planning to get the indication extended to Type 1 diabetics."
Phase II trials are earmarked to start at the end of the year and Phosphagenics is pegging its hopes on a three year timescale to market.
The company is eventually planning to licence the product to a big pharma firm to take it through to commercialisation.
"We are already seeing some really serious interest from within the industry for this product," said Preston.
The partner firm would be responsible for the formulation of the product, however Phosphagenics plans to keep control of the patented phosphorylation process, said Preston.
"We have developed a cost-effective, stable and cheap phosphorylation technique."
"There is no reason to believe our product won't be fully price-competitive with injectable insulin."
With over 200m diabetics worldwide and sales of injectable insulin of $5bn (€4bn) annually, Phosphagenics could be sitting on a potential goldmine.