Roche announces positive pivotal Phase II results for Hedgehog Pathway Inhibitor

RocheRoche (SIX: RO, ROG; OTCQX: RHHBY) 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, M.D., 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.

About the Phase II Trial (ERIVANCE BCC/SHH4476g)
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.

About Basal Cell Carcinoma
BCC is the most common type of skin cancer in Europe(1) Australia(2) and the USA.(3) The annual global incidence is around 2 million cases worldwide.(4,5,6) 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.

About vismodegib (RG3616/GDC-0449) and the Hedgehog Pathway
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 (U.S.), Roche (ex-U.S. 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.

About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2010, Roche had over 80'000 employees worldwide and invested over 9 billion Swiss francs in R&D. The Group posted sales of 47.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan.

1. N.R.Telfer, G.B.Colver and C.A.Morton. Guidelines for the management of basal cell carcinoma. The British Journal of Dermatology. 2008;158(7):35-48. Available at: http://www.bad.org.uk/Portals/_Bad/Guidelines/Clinical%20Guidelines/bcc%20Guidelines%20BJDJul08.pdf (Last accessed 15 March 2011)
2. Gilbody JS, et al. What causes basal cell carcinoma to be the commonest cancer? Aust J Public Health.1994; 18(2):218-21
3. Miller DL and Weinstock MA. Nonmelanoma skin cancer in the United States: incidence. Jam Acad Dermatol 1994; 30:774-8
4. World Health Organization: http://www.who.int/uv/faq/skincancer/en/index1.html Accessed August 10, 2010
5. Diepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol 2002;146(suppl):1-6
6. Rubin AI et al. Basal-cell carcinoma. N Engl J Med. 2005 Nov 24;353(21):2262-9

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