Vismodegib, First Hedgehog Inhibitor, Approved for BCC Patients

The FDA has approved vismodegib for the treatment of patients with basal cell carcinoma.

The FDA approves vismodegib to treat BCC

The FDA has approved vismodegib for the treatment of patients with basal cell carcinoma (BCC), marking the first cancer therapeutic targeting the Hedgehog pathway to gain authorization.

Vismodegib, which will be marketed under the trade name Erivedge, is indicated for adult patients whose cancer has returned after surgery or who have locally advanced or metastatic BCC that cannot be treated with radiation or surgery.

BCC is the most common form of skin cancer, accounting for approximately 75% of all cases, according to the National Institutes of Health. Although small tumors locally confined to the upper layer of the epidermis are considered treatable through surgical removal, advanced forms of BCC are difficult to treat and can leave patients disfigured and certain organs nonfunctioning after treatment.

In announcing its ruling, the FDA said Erivedge is the first drug approved for metastatic BCC and that it was reviewed under a priority program ahead of the March 8 goal date for a decision.

The FDA approved vismodegib based on the results of ERIVANCE study, which were first presented at the 7th European Association of Dermato-Oncology Congress in Nantes in June 2011.

The study found that the drug demonstrated objective response rates (ORR) for 43% of patients with locally advanced BCC and 30% of study participants with metastatic BCC. The median duration of response was 7.6 months.

In all, 104 participants were enrolled in the single-arm, open-label study, including 71 patients with locally advanced BCC whose lesions were either inoperable or who would have been deformed by surgery, and 33 patients whose disease had metastasized to either the lymph nodes, lungs, bones, or internal organs. The ORR was the primary endpoint.

Patients received 150-mg, once-daily oral doses until their disease progressed or they could not tolerate the toxicities. The most common adverse events included muscle spasms, hair loss, weight loss, and nausea, according to the FDA. The drug also carries a boxed warning about potential risk of death or birth effects to fetuses.

“This drug represents the only option that many of these patients have after other treatment options have failed them,” said Jennifer Low, MD, PhD, of Genentech BioOncology, who serves as the global development leader for vismodegib. “Otherwise, many of these patients might lose their eye, their ear, or other facial features because of this disease.”

The NIH estimates that BCC recurs in about 1% of patients who are treated with micrographic surgery and in 10% of patients who receive some other form of treatment.

The Hedgehog pathway is implicated in at least 19 different types of cancer. The pathway has been found to be active in approximately 90% of patients with BCC. Vismodegib specifically inhibits Smoothened, a transduction protein involved in the hedgehog pathway.

“Almost all cases of [BCC] have some sort of mutation of part of the Hedgehog pathway, which makes it an important target,” Low said.

Genentech, a member of the Roche Group, is responsible for the molecule’s discovery, and submitted the application for FDA approval last year. Curis, Inc collaborated with Genentech in preclinical studies.

Erivedge will be available in the United States within 2 weeks. Roche is pursuing marketing authorization in the European Union and patients there may be able to obtain the drug through a clinical trial.

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