Addressing unmet need
HedgePath Pharmaceuticals is pursuing treatment of BCCNS as its initial indication, although the molecular defect responsible for this genetic disease is also present in about 90% of sporadic BCCs and has been found in prostate, lung, and other tumors.
Two Hh pathway inhibitors are FDA approved--vismodegib (Erivedge, Genentech) and sonidegib (Odomzo, Sun Pharmaceutical). Both have indications for the treatment of adults with locally advanced BCC that has recurred following surgery or who are not candidates for surgery. Vismodegib is also approved to treat metastatic BCC.
In contrast to itraconazole, vismodegib and sonidegib are more potent Hh pathway inhibitors, but because of that activity, they are associated with more significant toxicity.
“In adults, the Hh pathway is also involved in tissue maintenance functions, and its inhibition by vismodegib and sonidegib causes hair loss, taste disturbances, muscle contraction, and nausea,” Virca said. “In clinical trials of vismodegib for BCCNS, there was a 54% dropout rate due to serious or intolerable side effects.”
Even if patients with BCCNS are able to obtain off-label insurance coverage for vismodegib and sonidegib, they may not be able to continue with chronic use that is needed to suppress tumor growth and development, Virca noted.
Because of a predilection for BCCs to develop on sun-exposed skin, an ophthalmologist may be the first physician to identify a patient with BCCNS, according to Dr. O’Donnell.
“Therefore, any ophthalmologist who sees a patient, especially a young person, with multiple BCCs around the eyes or elsewhere on the face should immediately suspect the diagnosis of BCCNS,” he said.
“The eyelid is one location where development of these tumors has real functional implications,” Dr. O’Donnell added. “There are just so many times that a patient can undergo surgical resection of eyelid lesions without developing exposure keratopathy and become at risk for irreversible loss of vision.”