NEJM hails vismodegib as ‘the greatest advance in therapy yet seen’ for advanced BCC

Vismodegib, a new skin cancer drug for patients with advanced basal cell carcinoma tested by TGen, Virginia G. Piper Cancer Center at Scottsdale Healthcare and Mayo Clinic, is hailed as "the greatest advance in therapy yet seen" for advanced basal cell carcinoma in an editorial in the New England Journal of Medicine.

Vismodegib (marketed under the name Erivedge) was administered for the first time in the world on Jan. 23, 2007 in a Phase I clinical trial at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, a partnership with the Translational Genomics Research Institute (TGen).

This is the first drug tested under the Scottsdale Healthcare-TGen partnership to receive FDA approval, and is the first to receive FDA approval to treat inoperable basal cell carcinoma. Successful early trial results led to additional study sponsored by Genentech.

The successful Phase I study at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, headed by Scottsdale Healthcare Chief Scientific Officer and TGen Physician-In-Chief Daniel Von Hoff, M.D, led to a broader study, published June 7 by the New England Journal of Medicine.

"The first patient put on this drug had advanced basal cell cancer, so we suspected that the tumor had the mutation this drug is targeted against," said Ramesh K. Ramanathan, M.D., Medical Director at Virginia G. Piper Cancer Center Clinical Trials and Clinical Professor and Deputy Director of the Clinical Translational Research Division at TGen. "And our partnership with Dr. Ronald Korn and his team who did advanced PET imaging helped to really demonstrate the drug's efficacy for Genentech to continue pursuing the additional study."

The follow-up study, a Phase 2 clinical trial of basal cell carcinoma (BCC), was headed by Dr. Aleksandar Sekulic, Assistant Professor of Dermatology for the Mayo Clinic in Arizona, and an Assistant Professor in TGen's Integrated Cancer Genomics Division.

This Phase 2 study provided the efficacy data for vismodegib that led to its approval by the U.S. Food and Drug Administration (FDA) on Jan. 30, 2012.

"As a result of a strong collaboration between the Valley institutions, clinical development of this new medication, from the first clinical trial to the FDA approval, was led by the Valley researchers," said Dr. Sekulic, M.D and Ph.D., whose study found that vismodegib shrank advanced basal cell carcinoma tumors in 43 percent of patients with locally advanced disease and in 30 percent of patients whose disease spread to other organs.

The drug blocks the Hedgehog signaling pathway and was approved for treatment of locally advanced and metastatic basal cell carcinomas. Additional research noted encouraging results for patients with inherited genetic susceptibility for development of large numbers of BCC tumors, known as basal cell nevus syndrome.

"The availability of vismodegib and similar medications will really change the way we treat the patients with advanced forms of BCC, who had very limited options to date. In addition, this drug will likely offer a life-changing treatment for patients with basal cell nevus syndrome. It is possible that the drug may also be of benefit in treatment of earlier stages of BCC, and this is currently being evaluated in several clinical trials," Dr. Sekulic said.

"It is a landmark day for patients with basal cell carcinoma and all those involved in their care," said the NEJM editorial. However the editors cautioned that additional study of Hedgehog pathway inhibitors like vismodegib warrant further study so a larger number of patients may benefit.

FDA approval in five years is a remarkable achievement because clinical trials typically progress through three phases and can take up to 15 years to successfully complete, according to Mark Slater, Ph.D., Vice President of Research at Scottsdale Healthcare.

Most instances of basal cell cancer can be effectively treated, but in some cases, the cancer cells spread and develop an aggressive form of the cancer that does not respond to standard surgical treatment.

"For a small percentage of patients, basal cell carcinoma can progress to inoperable life-threatening, locally advanced or metastatic tumors. Vismodegib, taken as a once a day pill, represents an opportunity to improve quality of life for these patients," said Dr. Glen Weiss, Director of Thoracic Oncology at Virginia G. Piper Cancer Center Clinical Trials and Clinical Associate Professor of TGen's Cancer and Cell Biology Division.