Oxycodone is an opioid drug which is more potent than morphine, and demonstrates fewer adverse effects in patients. Consequentially, it is a leading pain management drug for the treatment of moderate to severe pain. It is currently administered in tablet or intravenous form.
Global opioid revenue for 2010 has been forecast to be in excess of USD 10.5 billion. The superior properties of oxycodone in pain relief resulted in an almost 900% increase in patient use in the decade to 2007. Oxycodone-based drugs generate revenues in excess of $4-5 billion per annum, with Oxycontin alone posting sales of approximately $3.88 billion in 2010.
Phosphagenics is working towards becoming the first to provide chronic pain sufferers with a patch that will provide sustained-release of oxycodone into the bloodstream. Clinical trials to date have demonstrated that Phosphagenics’ novel technology can effectively deliver opiates through the skin without causing irritation. A transdermal product is desirable to reduce or eliminate GI tract side effects, and achieve a sustained therapeutic profile. A further advantage of a matrix patch is the opportunity to produce an abuse resistant product.
The TPM/oxycodone patch has been designed using a polymer matrix that makes drug extraction inherently difficult. Anti-abuse properties are critical in order to gain acceptance from registration authorities and regulatory bodies such as the FDA.
Phosphagenics conducted three clinical studies between 2009-2010 on its TPM/oxycodone formulation, both with successful results. The first study, an open-label, human Repeat Insult Patch Test (RIPT) evaluated the skin response of fifty healthy participants with both an induction phase and a challenge phase. The study concluded that no significant erythema or sensitisation were observed.
The second study, a Repeat Dose Application study, was an open label, single centre pharmacokinetic study in 20 healthy volunteers conducted at the Royal Adelaide Hospital. Its primary objective was to compare the delivery profiles of two transdermal patch candidates containing TPM®, a matrix and a reservoir system, following daily application over a ten-day period. The study reported positive results using the company’s proprietary TPM® (Targeted Penetration Matrix) technology for the transdermal delivery of oxycodone and revealed that daily application of the TPM/oxycodone patch delivered therapeutic bloodstream levels of oxycodone in a reproducible, consistent and sustained manner, again with no irritation observed.
A third study, completed in October 2010, was led by Professor Guy Ludbrook at the Royal Adelaide Hospital. This milestone study was designed to compare various dosage regimes of the TPM/oxycodone patch. Importantly, the study demonstrated that the extended dosing period of 14 days enabled steady state delivery of oxycodone into the bloodstream to be achieved.
In November 2010 Phosphagenics announced signing a collaborative consultancy agreement with 3M for the optimisation and development of a commercial scale up manufacturing process.
3M’s expertise in drug delivery technologies had assisted Phosphagenics to improve the delivery profile of the original patch prototype.
However, crystallisation issues with the patch meant that in order to finish Phosphagenics engaged the services of Labtec GmbH, a Germany company, which had expertise in the area of opioid patch technology. The new patch was completed in early 2013 and in May 2013 a single dose study was commenced. The trial results announced in July indicated that the oxycodone patch would be suitable for peripheral and neuropathic pain.
A Phase 2 trial is the next phase contemplated in order to establish proof of concept and efficacy. Whilst there is some anecdotal evidence that opioids can give pain relief via topical application, there dos not appear to be any companies that have taken a topical opioid to the clinic.