LEO Plays Up Rapid Action Of Picato For Actinic Keratosis
This article was originally published in The Pink Sheet Daily
Executive Summary
Newly approved plant-based gel works in just a few days of treatment, rather than the weeks required for some competitors.
Privately-held Danish firm Leo Pharma ASis playing up the fact that its just-approved, plant-based Picato gel treats the precancerous skin lesions known as actinic keratoses in just a few days, rather than the six to sixteen weeks for some topical cream competitors.
Two strengths of Picato (ingenol mebutate) gel were approved by FDA (0.015%, 0.05%) Jan. 23. LEO is planning to launch in the U.S. at the end of the first quarter or the beginning of the second quarter, President and CEO John Koconis said in an interview on Jan. 25, when the approval was announced.
AKs are sun-induced rough spots that can develop into squamous carcinomas, the second most common kind of skin cancer. According to the Skin Cancer Foundation, some 58 million Americans have AK.
Picato is taken from the milky sap of a plant called radium weed – or Euphorbia peplus – which has been used traditionally as a treatment for skin conditions. It is thought that the treatment induces cell death, but the mechanism of action isn’t fully understood.
The 0.015% formulation of Picato was approved for treatment of lesions on the face and scalp once daily for three consecutive days; the 0.05% gel is cleared for once-daily treatment of the trunk and extremities for three consecutive days. The gel may be applied to the affected area, up to one contiguous skin area of about 25 cm2, as this is what was tested in pivotal trials, but some say off-label use in larger areas of skin is likely .
LEO picked up the treatment via its acquisition of Aussie biotech Peplin Ltd. for $287.5 million in cash in September 2009 and the company plans to manufacture the natural treatment in Australia (Also see "Skin Tight: Dermatology Specialty Leo Pharma To Buy Peplin for $287.5 Million" - Pink Sheet, 3 Sep, 2009.).
Cryotherapy is the dominant treatment for AK, but topical creams also have a role in the dermatologists’ armamentarium. Koconis estimates the topical cream market in the U.S. is worth $200 million and that Picato has the opportunity to expand that significantly.
One of the leading treatments is the generic imiquimod cream 5%, or Aldara from Graceway Pharmaceuticals LLC, which involves a twice-weekly treatment for a total of 16 weeks. Due to the patent expiration, Aldara product revenue fell from $320 million in 2009 to $52.2 million in 2010.
In March 2011, Graceway won approval for its follow-on treatment Zyclara, a 3.75% cream that has a much shorter dosing regimen of six weeks, including two weeks of daily treatment, two weeks of non-treatment, and then another two weeks of daily treatment. Zyclara also has the advantage of being approved for use on larger area of skin – the full face or balding scalp – whereas like Picato, Aldara is cleared only for treating a 25 cm2 area of skin.
Medicis Pharmaceutical Corp. acquired Graceway at the end of 2011 in a bankruptcy auction and now markets Zyclara (Also see "Medicis Plans To Build On Zyclara After Graceway Acquisition" - Pink Sheet, 6 Dec, 2011.).
Other topical options include various generic versions of the chemotherapy drug fluorouracil, which according to the label, may be given twice daily for two to six weeks. Prescribing information warns that reaction to treatment can be “unsightly” during therapy and in some cases this effect can last for several weeks after treatment. Labeling does not restrict the size of the area treated.
Approval of Picato was supported by four double-blind, vehicle (placebo) controlled trials of about 1,000 patients, two of which were done in the trunk and extremities, and the other two in the neck and scalp.
In the trunk and extremity studies, the gel had a complete clearance rate (100% of lesions gone) of 28% and 42% compared to 5% for the vehicle control in both studies. And the partial clearance rates (at least 75% of lesions cleared) were 44% and 55%, versus 7% for the vehicle control in both studies.
In the face and scalp studies, the complete clearance rates were 37% and 47%, versus 2% and 5% for controls. And the partial clearance rates came in at 60% and 68% vs. 7% and 8% for vehicle controls. The most common adverse events ware local skin reactions, application site pain and application site pruritus.
For Zyclara 3.75%, the rate of complete clearance in two, randomized controlled studies of actinic keratosis were 26% and 46%, versus 3% and 10% for vehicle control. And rates of partial clearance greater than or equal to 75%, were 46% to 73%, versus 19% and 27%.
In two studies of Aldara, the complete clearance rates were 46% and 44% vs. 3% and 4% for vehicle. And the partial clearance rates were 60% and 58% vs. 10% and 14% for vehicle.