New drug applications submitted in the United States and Europe for vemurafenib in advanced skin cancer

RocheRoche (SIX: RO, ROG; OTCQX: RHHBY) announced that the company submitted a New Drug Application for vemurafenib (RG7204, PLX4032) to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application to the European Medicines Agency (EMA) for approval for people with BRAF V600 mutation-positive metastatic melanoma. Roche also submitted an application for the cobas 4800 BRAF V600 Mutation Test, a companion diagnostic. Vemurafenib, a "BRAF-inhibitor", is designed to selectively target and inhibit a mutated form of the BRAF protein found in about half of all cases of melanoma, the deadliest and most aggressive form of skin cancer.

"We have worked swiftly to advance the vemurafenib development programme knowing that patients with metastatic melanoma have a poor prognosis and limited treatment options," said Hal Barron M.D., Chief Medical Officer and Head, Global Product Development. "The regulatory submissions of vemurafenib and the companion diagnostic to identify people with the type of melanoma specifically targeted by this medicine are exciting steps toward our goal of delivering a personalized therapy for this disease."

The submissions are based on results from two positive clinical studies (BRIM2 and BRIM3) that evaluated vemurafenib in people with BRAF V600 mutation-positive metastatic melanoma, as determined by the investigational companion diagnostic test also being developed by Roche. A Premarket Approval Application for the cobas 4800 BRAF V600 Mutation Test was submitted in the U.S. The test will also will also be registered in Europe.

About metastatic melanoma and BRAF
When melanoma is diagnosed early, it is generally a curable disease. However, when it spreads to other parts of the body, it is the deadliest and most aggressive form of skin cancer. A person with metastatic melanoma typically has on average a short life expectancy that is measured in months. Less than one in four people are expected to be alive one year after a diagnosis and every year there are an estimated 40,000 deaths worldwide from the disease.(1)

The BRAF protein is a key component of the RAS-RAF pathway involved in normal cell growth and survival. Mutations that keep the BRAF protein in an active state may cause excessive signalling in the pathway, leading to uncontrolled cell growth. These mutations of the BRAF protein are thought to occur in an estimated half of all melanomas and eight percent of solid tumours.

About BRIM3 and BRIM2
BRIM3 is a global, randomised, open-label, controlled, multicentre, Phase III study that compared vemurafenib to dacarbazine chemotherapy, a current standard of care, in 675 patients with previously untreated BRAF V600 mutation-positive, unresected or locally advanced metastatic melanoma. The study met its two co-primary endpoints and showed that participants who received vemurafenib lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival) compared to those who received dacarbazine chemotherapy. The safety profile was consistent with previous vemurafenib studies.

Full data from BRIM3 will be presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) on June 5, 2011 in Chicago.

BRIM2 is a global, single-arm, multicentre, open-label Phase II study that enrolled 132 patients with previously treated BRAF V600 mutation-positive metastatic melanoma. The primary endpoint of the study was overall response rate as assessed by an independent review committee. The study showed that vemurafenib shrank tumours in 52 percent of trial participants. People who participated in the trial lived a median of 6.2 months without their disease getting worse (median PFS). Updated data from BRIM2 will also be presented at the ASCO Annual Meeting.

The most frequent Grade 3 adverse event observed in clinical trials of vemurafenib was cutaneous squamous cell carcinoma, a common skin cancer treated by local excision (minor surgery done in a physician's office). The most common adverse events were rash, photosensitivity, joint pain, hair loss and fatigue.

About vemurafenib
Vemurafenib (pronounced vem oo RAF en ib) is an investigational, oral, small molecule that is designed to selectively inhibit a cancer-driving mutated form of the BRAF protein. Vemurafenib is being co-developed under a 2006 license and collaboration agreement between Roche/Genentech and Plexxikon. The cobas 4800 BRAF V600 Mutation Test is an investigational, polymerase chain reaction-based companion diagnostic being developed by Roche to identify people whose tumours carry the BRAF V600 mutation.

Roche is considering a broad development program with vemurafenib that may include combinations with other medicines (both approved and investigational, from Roche and other companies), as well as studies in other tumour types. While Roche seeks approval of the drug, vemurafenib is available to eligible patients with BRAF V600 mutation-positive metastatic melanoma through a global patient access program.

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 almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 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. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55:74–108.

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