Roche announced that a pivotal phase II clinical study of its investigational Hedgehog Pathway Inhibitor, vismodegib (RG3616/GDC-0449), showed positive results in people with advanced Basal Cell Carcinoma (aBCC), a particularly severe and debilitating form of skin cancer. The study met its primary endpoint (overall response rate), of showing vismodegib shrank tumours in a pre-defined percentage of people in the study. A preliminary safety assessment showed the most common adverse events were consistent with previous experience with vismodegib. A detailed safety assessment is ongoing.

“These results are important because people with this disfiguring and potentially life-threatening advanced form of skin cancer currently have no approved treatment options,” said Hal Barron, MD, chief medical officer and Head Global Product Development. “We look forward to presenting the study data in more detail and discussing the results with global health authorities.”

Data from the study will be submitted for presentation at a future medical meeting. The Hedgehog signalling pathway plays an important role in regulating proper growth and development in the early stages of life and then becomes less active in adults. However, mutations in the pathway that reactivate Hedgehog signalling are seen in several different types of cancer. Abnormal signalling in the Hedgehog pathway is implicated in the majority of BCC cases.

Roche is also evaluating vismodegib in a phase II trial in people with operable forms of BCC, which opened in October 2010.

Erivance BCC is an international, single-arm, multi-centre, two-cohort, open-label Phase II study that enrolled 104 patients with aBCC, including locally advanced and/or metastatic BCC, defined as patients whose lesions are not appropriate for surgery, or for whom surgery would result in substantial deformity. Study participants received 150mg vismodegib once daily until disease progression.

The primary endpoint of the study was overall response rate (tumour shrinkage), as assessed by independent reviewers. Secondary endpoints of the study included overall response rate as assessed by study investigators, duration of response, progression-free survival, overall survival and the safety profile. A preliminary safety assessment showed the most common adverse events were muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite and diarrhoea. Serious adverse events were seen, including fatal events. The deaths are being further evaluated but do not appear to be related to vismodegib.

BCC is the most common type of skin cancer in Europe Australia and the USA. The annual global incidence is around 2 million cases worldwide. The disease is generally considered curable when the cancer is restricted to a small area of the skin. However, in a small group of people, if the disease is left untreated or does not respond to treatment, the cancer may advance further into the skin, bones or other tissues. In a small proportion of patients (estimated at less than 1%), BCC can advance or spread to other parts of the body and can become difficult to treat or life-threatening.

GDC-0449 now has a generic name approved by the World Health Organisation, vismodegib (pronounced vis-mo-DE-jib). Vismodegib is a first-in-class investigational, oral medicine that is designed to selectively inhibit signalling in the Hedgehog pathway by targeting a protein called Smoothened.

Roche is developing vismodegib under a collaboration agreement with Curis, Inc. Vismodegib was discovered by Genentech and jointly validated by Genentech and Curis through a series of preclinical studies. Through this collaboration, Genentech (US), Roche (ex-US excluding Japan) and Chugai Pharmaceuticals (Japan) are responsible for the clinical development and commercialization of vismodegib. Curis is eligible to receive cash payments upon the successful achievement of specified clinical development and regulatory approval milestones, as well as royalties upon commercialization of vismodegib.