Staff Writer

A pivotal Phase II study of oral medicine vismodegib (RG3616/GDC-0449) showed positive results in people with inoperable, advanced basal cell carcinoma (BCC), a rare form of skin cancer, reported Genentech Inc., of South San Francisco, a member of the Roche Group.

The company, which presented full data at the Seventh European Association of Dermato-Oncology Congress in Nantes, France, said the hedgehog pathway inhibitor substantially shrank tumors or healed visible lesions in 43 percent of patients with locally advanced BCC and 30 percent of patients with metastatic BCC. In March, Genentech reported that the primary endpoint, overall response rate, had been met. The Phase II study, ERIVANCE BCC, enrolled 104 patients.

Genentech expects to file a new drug application with the FDA by the end of 2011, and is also planning a European approval path, Genentech spokeswoman Charlotte Arnold told BioWorld Today. The company said that ERIVANCE BCC, an international, single-arm, two-cohort, open-label trial at 31 sites in the U.S., Australia and Europe, was designed as a registrational study in consultation with the FDA. Genentech said that investigators assessed the median duration of progression-free survival for both metastatic and locally advanced BCC patients as 9.5 months.

There currently are limited treatment options and no standard of care for the treatment of inoperable advanced BCC, Genentech said, adding that it is conducting an expanded patient access study in the U.S. to provide people with advanced BCC access to vismodegib.

In most cases, the company said, BCC is generally considered curable if the cancer is restricted to a small area of the skin, but if it is not treated or recurs after surgery, the cancer may invade the ears, nose, eyes, bones and other parts of the body.

Some analysts estimated the market opportunity for the rare Inoperable BCC at between $150 million and $300 million, but added that there are potentially larger opportunities for operable BCC and cancers other than BCC. Genentech in late 2010 began a Phase II study of patients with operable BCC, which the American Cancer Society estimated accounts for about 80 percent of the nearly 1.6 million new skin cancers cases diagnosed annually.

Rodman & Renshaw analyst Reni Benjamin wrote recently that the BCC indications are just stepping stones to bigger markets. BCC is just one of several currently being evaluated by Roche/Genentech and clinical investigators from the National Cancer Institute, he said. Others include medulloblastoma, sarcoma, glioblastoma, pancreatic, small-cell lung cancer, gastroesophageal, stomach, breast and prostate cancers.

He added that Roche/Genentech's decision to pursue regulatory filings in the U.S. and EU "reflects a high degree of confidence in the efficacy results for [vismodegib] and indicates that the findings are unambiguous and actionable."

Vismodegib was discovered by Genentech and validated in preclinical studies with partner Curis Inc., of Lexington, Mass. Curis President and CEO Dan Passeri told BioWorld Today that as part of the collaboration agreement signed in June 2003, Curis received $8.5 million up front and an estimated $15 million in research support from Genentech that helped reduce Curis' burn rate.

To date, Curis has received an additional $18 million of a potential $115 million in milestones, with U.S. and EU new drug applications the next milestones. Curis also is eligible for sale royalties in the mid-to-upper single digits.

Roth Capital Partners analyst Joseph Pantginis estimated Curis' royalty revenue at about 8 percent of peak sales of $275 million of vismodegib for inoperable BCC. "Further upside could come from the larger operable BCC indication, though we do not project approval until 2017," he said.

Clinical development and commercialization of vismodegib are the responsibilities of Genentech in the U.S., Roche outside the U.S. excluding Japan, and Chugai Pharmaceuticals in Japan.

In April, Curis presented interim Phase II data on vismodegib in patients with basal cell nevus syndrome, also known as Gorlin syndrome. The data demonstrated proof of concept for the therapeutic utility of vismodegib for BCC in Gorlin syndrome patients, for whom no pharmacological standard-of-care intervention is approved. The Phase II double-blind, randomized placebo-controlled, two-arm multicenter study of vismodegib enrolled 41 patients from September 2009 to January.