Phosphagenics delivers promising morphine results

Melbourne pharma Phosphagenics (ASX:POH) has demonstrated that its patented TPM-01 transdermal delivery system can administer morphine safely and efficiently through the skin, to maintain therapeutic levels of the drug in the serum over a period of at least 48 hours.

The Phase I, proof-of-concept trial has delivered "exceptionally promising" results, according to the company's announcement today, and it is now planning a Phase II efficacy trial.

Dr Esra Ogru, VP research and development, described the results as a milestone for Phosphagenics, and confirmed TPM-01 as a novel platform technology for delivering morphine and other drugs through the skin.

The company described its success with transdermal morphine as a world first. It has previously demonstrated transdermal delivery of the heart drug atropine, and the hormones estradiol and testosterone using TPM-01 as a carrier.

The trial involved 10 healthy male volunteers, who received a single application to the skin of a mixture of TPM-01 and 100mg of morphine to the skin of the inner upper arm.

Monitoring of the drug in the volunteers' serum showed its level peaked within four hours after the treatment was administered, and remained approximately constant, at therapeutic concentrations, for up to 48 hours.

Applied in native form to the skin, the opiate causes redness and irritation, but the Phosphagenics trial recorded no adverse side-effects, and the treatment was well tolerated.

Ogru said several drug companies have tried unsuccessfully to develop a transdermal form of morphine, because it would reduce the undesirable side-effects of intravenous, oral or intramuscular delivery.

Bolus dosing via the oral or intramuscular route produces a strong peak in the blood, followed by a rapid and steady decline. Ogru said that while morphine is non-addictive when given to control strong pain, such as post-operative pain or the chronic pain of advanced cancer, there is a higher risk of addiction associated with sharp peaks in the blood.

Extended-release forms of insulin are safer, and produce fewer side effects, but the only extended-release formulations currently available are oral products, and are effective for only 12 to 24 hours per dose. Phosphagenics' transdermal formulation, applied via a skin patch, could double this interval.

"We expect that a transdermal morphine product will be well accepted in the global US $6.0 billion market for pain management using narcotic medications," Ogru said.

She said the company now plans to test the TPM-01 delivery system on other opiates, including naloxone and naltrexone.

She said there was increasing evidence from the company's research that TPM-01, a highly phosphorylated molecule that conjugates readily to small-molecule drugs, facilitates the uptake of drugs by natural receptors or transporter proteins in the skin.

The current study was half-funded through a $1.7 million R&D START grant from AusIndustry; the company matched the grant from its own sources.