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The commercialization of ingenol mebutate (Picato, LEO Pharma) a medication that is currently approved in the United States and many other countries for the treatment of actinic keratosis, is an example of how enthusiasm and commitment can drive innovation, a LEO Pharma general manager says.
Montreal - The commercialization of ingenol mebutate (Picato, LEO Pharma) a medication that is currently approved in the United States and many other countries for the treatment of actinic keratosis, is an example of how enthusiasm and commitment can drive innovation, a LEO Pharma general manager says.
“It doesn’t take a large, multi-national pharmaceutical company to develop a new product,” says Peter Welburn, Ph.D., general manager, Australia/New Zealand, LEO Pharma. He was based at GlaxoSmithKline in Brussels, and returned to his native country of Australia in 2000 to join a then fledgling pharmaceutical firm known as Peplin. “It takes passion, and it takes dedication.”
Speaking here at an update on therapeutics in dermatology, Dr. Welburn says it’s a tremendous opportunity to be involved in taking a concept all the way to the pharmacy shelf. With the success of its flagship product ingenol mebutate, Peplin was acquired in 2009 by LEO Pharma.
Dr. Welburn recounts that many challenges faced a small research and development team at Peplin, including securing a source of plant material from which the sap of the plant Euphobhia peplus could be extracted.
“Our research and development team in Australia never consisted of more than six people,” Dr. Welburn says.
Dr. Welburn and other Peplin staff approached local farmers in Australia, asking them to grow this plant for the purposes of extraction and to use the plant on a commercial basis; several farmers initially agreed.
There has been documented use of E. peplus for skin cancer and solar keratosis with few side effects, Dr. Welburn notes. The anecdotal experience served to provide a foundation for clinical trials to examine the efficacy and safety of the compound in the treatment of nonmelanoma skin cancer.
“We needed to develop a clinical department, and needed to start doing clinical trials,” Dr. Welburn says. “We had to draw on the experience of key opinion leaders.”
Another challenge was attaining stability of the molecule, he says.
“We faced significant challenges in wondering how to stabilize this molecule and put it in an appropriate topical formulation,” Dr. Welburn says. “For long-term stability of the topical formulation, it needs to be refrigerated. It took us about six months to determine that.”
Many dose-ranging studies were conducted to determine the optimal dosing regimen, he says. The significant advantage of the therapy is the short course of treatment, anywhere from two to three days.
It is noteworthy that this therapy was developed in Australia, a jurisdiction where skin cancer represents a significant treatment burden for dermatologists, according to Dr. Welburn.
Skin cancers represent 80 percent of all newly diagnosed cancers in Australia, and Australia has an incidence of skin cancer that is one of the highest in the world, two to three times the rates in the United States and the United Kingdom, according to the Cancer Council of Australia.
Innovative thinking is what has prompted the emergence of therapies such as Picato, which many maintain will improve adherence to treatment regimens, according to Stuart Maddin, M.D., F.R.C.P.C., clinical professor emeritus, department of dermatology and skin science, University of British Columbia, Vancouver.
“The major factor associated with this drug is that it is used over a period of two to three days, which truncates the treatment span, and this is most appreciated by patients,” Dr. Welburn says. “I think it will go a long way to achieving enhanced compliance.”
Other emerging skin cancer therapies include the BRAF-inhibitor dabrafenib (Tafinlar, GlaxoSmithKline), Dr. Maddin says. While there are numerous side effects for a drug like dabrafenib - such as kidney failure and fevers - Dr. Maddin points out that it is employed for very advanced cases of melanoma.
“The indication is for end-stage metastatic melanoma,” Dr. Maddin says.
Trametinib, a MEK inhibitor, is a first in its class therapy, which also produces serious adverse events such as heart failure and loss of vision. Like dabrafenib, it is indicated for the treatment of metastatic melanoma and taken orally. The Food and Drug Administration on Jan. 10 approved trametinib (Mekinist, GlaxoSmithKline) in combination with dabrafenib for the treatment of patients with advanced melanoma that is either unresectable or metastatic.
Disclosures: Dr. Welburn is general manager, Australia/New Zealand, LEO Pharma.