15 Aug 2013
Ondine Biomedical believes PDT can overcome the hurdles that have held the technology back.
Earlier this year a LASER 2013 session discussing biophotonics summarized the situation, in particular in relation to PDT's potential role in cancer treatment. It noted that a number of promising case studies had shown its effectiveness, but not led to the kind of large-scale trials needed to persuade clinicians and regulators of the technique's worth, leaving PDT stuck in its own particular Catch-22 scenario.
Carolyn Cross, founder and CEO of Ondine Biomedical, Vancouver, is familiar with the dilemma. Ondine describes itself as an incubator, developing PDT-based non-antibiotic therapies for the treatment of bacterial, fungal and viral infections.
The company's four current product platforms are targeted at four distinct procedures: treatment of bacteria in the periodontium; treatment of the nasal passages, particularly as a route to tackle hospital-acquired infections such as MRSA; eliminating pathogens in the birth canal, such as HIV; and disinfecting endotracheal tubes used when patients require mechanical ventilation.
Ondine refers to its PDT process as photodisinfection, or antimicrobial application of PDT (aPDT). The four platforms, currently at various stages of development and regulatory approval, are based on the established principles of PDT, by which photosensitive species applied to the treatment site preferentially bind to the targeted microbes.
The added molecules are initially inactive, but when illuminated by a laser of a specific wavelength and intensity a photocatalytic reaction occurs, generating short-lived, highly reactive free-radical oxygen species that destroy the targeted microbes without damage to the host cells. Turning off the irradiation halts the process in its tracks.
Financial and clinical factors
Carolyn Cross agrees with the general sentiment that PDT, for all its advantages as a technique, has not as yet become as well-established as its advocates would wish.
"It is true that a number of significant, but not insurmountable, individual barriers have had negative consequences for PDT adoption, and that it has not done as well as it should have," she told Optics.org. "But the biggest testament to its efficacy is that it is still around today, despite 30 years of poor corporate and government support, held together by a passionate scientific and clinical community that understands the truly exceptional benefits both to patient and payer that it offers."International Photodynamic Association (IPA) on the regulatory issues facing the PDT community, the barriers have never stemmed from any reluctance to embrace the technology on the part of patients. Instead, the hurdles have centered on financial and clinical factors, particularly around the logistics of clinical trials and the need for suitable capital investment.
"Governments typically do not fund pivotal trials, limiting themselves to the exploratory and early stage work, with the expectation that companies will then take the developments forward," she said. "But clinicians need a great deal of data to justify a change from their well known protocols, and the number and size of the trials needed is too large for any small company to undertake - or indeed for large companies to justify, given the need to maintain short term profit margins. So in practice, they are not done."
Breaking this logjam for PDT will require advocacy from key opinion leaders in different territories, with access to both the technology and funding for small trials and training - a process Cross agrees would be expensive and time consuming, perhaps beyond the resources of most small developers.
Another financial hurdle is the reimbursement clinicians receive for adopting PDT, a problem shared with other emerging biophotonics platforms. Unless clinicians receive reimbursement for a new technology right from the start, the uptake can be very small.
An answer to that could be governmental involvement. Cross advocates that the US Medicare/Medicaid systems should mandate PDT as a first-choice treatment, and would like to see a similar approach from publicly-funded health systems in the EU and Canada. But at present, there appears to be no avenue for PDT to make inroads into Government bureaucracy.
PDT is here to stay
Capital investment is an additional and inevitable barrier, given Cross's belief that there has been insufficient capital to support product and protocol development in PDT throughout its 30 years as a viable technology.
"Large companies, with the cash hordes from other products, do not have the ability to invest, given their need for short term profit goals; and small companies cannot attract this capital due to risks and lengthy time horizons," Cross said. The result is small-scale or philanthropic efforts that only move PDT forward slowly.
One factor that will influence the situation should arrive when developing economies such as Brazil, Russia, India and China (known as the BRIC economies), embrace cheaper clinical technologies out of financial necessity. Cross feels there is now a growing collective force promoting greater cooperation and partnership with the BRICs on PDT issues, driven by the IPA and the PanAmerican PDT Association.
Once that happens, the trials and experience in those territories could spill over into the developed markets, a process that would accelerate if developers in both camps joined forces. That way, profitability derived from the BRIC territories could support marketing and reimbursement trials in the developed areas.
For its part, Ondine is aiming to push its platform technology into fresh application areas where new patients can be found. It has licensed aPDT to Sinuwave Technologies, a spin-out from Ondine founded in 2010 that focuses on commercialization of photodisinfection treatments for chronic sinusitis. Finding similar new applications that serve unmet needs is now the key to boosting PDT's success, according to Cross.
"PDT is here to stay, because of its efficacy and safety profiles that materially improve quality of life and other patient outcomes," she said. "It must be championed in the absence of better alternatives. Very talented people have done very serious science into PDT for over 30 years, and our collective resolve to see it succeed is only getting stronger."
About the Author
Tim Hayes is a contributing editor to Optics.org.