Roche’s Zelboraf receives EU approval

Roche (SIX: RO, ROG; OTCQX: RHHBY), today announced that the European Commission has approved Zelboraf (vemurafenib) as a monotherapy for the treatment of adult patients with BRAF V600 mutationpositive unresectable or metastatic melanoma, the most aggressive form of skin cancer. Zelboraf is designed to target and inhibit mutated forms of the BRAF protein found in about half of all cases of melanoma.

“Today’s approval is important news for people with BRAF mutation-positive metastatic melanoma as Zelboraf significantly improves patient survival and exemplifies the benefits that Roche’s personalized approach to medicine can provide for patients, physicians and society,” said Hal Barron, M.D., Chief Medical Officer and Head, Global Product Development.

In pivotal clinical trials, Zelboraf is the only treatment to benefit patient survival in both previously untreated and previously treated people with advanced melanoma who tested positive for BRAF V600 mutations using the Roche cobas 4800 BRAF V600 Mutation Test.

• In the pre-specified interim analysis of the phase III BRIM3 trial, the risk of death was reduced by 63 percent for people who received Zelboraf compared to those who received standard first-line treatment (hazard ratio [HR]=0.37, p<0.0001).
• In a post-hoc analysis of BRIM3 data with a longer follow up compared to previous analyses, including cross-over of patients from the placebo to the active treatment arm, Zelboraf significantly improved survival over standard first-line treatment by providing a median overall survival (OS) of 13.2 months compared to 9.6 months for chemotherapy (hazard ratio [HR]=0.62)
• A survival benefit was also shown in pre-treated patients in the phase II BRIM2 study, the data from which is planned to be published shortly.

In 2011, Zelboraf became the first and only US FDA approved personalised medicine that is shown to improve survival for people with BRAF V600 mutation-positive unresectable or metastatic melanoma. The cobas 4800 BRAF V600 Mutation Test, a diagnostic test co-developed by Roche to identify patients eligible for treatment, was approved simultaneously with Zelboraf in the US, and is CE-marked and commercially available in the EU.

Zelboraf has also recently been approved in Switzerland, Brazil, Israel, Canada and New Zealand and marketing authorization submissions are currently under review by health authorities in Australia, India and other countries worldwide. While Roche seeks regulatory approval of Zelboraf in other countries, a global safety study is providing access to Zelboraf for over 2000 people with previously treated or untreated BRAF V600 mutation-positive metastatic melanoma.

Zelboraf safety

The safety profile of Zelboraf was generally consistent in all clinical studies. The most common grade 3 or higher adverse events seen more often in people receiving Zelboraf compared to those receiving chemotherapy were a common type of skin cancer, cutaneous squamous cell carcinoma (cSCC) including keratoacanthomas, rash, liver function abnormalities, joint pain and sensitivity to the sun. In cases of cSCC, the lesions were generally removed and the patients continued with treatment.

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. Only around one in four people with metastatic melanoma are expected to be alive one year after their diagnosisⁱ.

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 and survival. These mutations of the BRAF protein are thought to occur in an estimated half of all melanomas and eight percent of solid tumours.

About BRAF V600 mutation testing

The cobas 4800 BRAF V600 Mutation Test is a polymerase chain reaction-based diagnostic test developed by Roche. This EU (CE-marked), FDA-approved test was clinically validated in the BRIM2 and BRIM3 studies to identify tumours that carry the BRAF V600E mutation. The test has several advantages compared to Sanger sequencing, a commonly used method, including greater sensitivity and reliability for detecting mutations and quicker results, allowing doctors to know whether a person with metastatic melanoma is eligible for treatment with Zelboraf.

About BRIM3 and BRIM2

BRIM3 is a global, randomised, open-label, controlled, multicentre, phase III study that compared Zelboraf to dacarbazine chemotherapy, a standard of care, in 675 patients with previously untreated BRAF V600E mutation-positive, unresectable or metastatic melanoma. BRIM2 is a global, single-arm, multicentre, openlabel phase II study that enrolled 132 patients with previously treated BRAF V600E mutation-positive metastatic melanoma.

About Zelboraf

Zelboraf is an oral, small molecule, kinase inhibitor indicated for the monotherapy treatment of adult patients with BRAF V600 mutation positive unresectable or metastatic melanoma. Zelboraf is not recommended for use in melanoma patients with wild-type BRAF. Zelboraf is being co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon, a member of the Daiichi Sankyo Group. Roche and Genentech are conducting a broad development program with Zelboraf that includes testing combinations with other medicines (both approved and investigational, from Roche/Genentech and other companies), as well as studies in other tumour types. More information about this program or other Zelboraf studies is available at the Roche Clinical Trials Registry at www.roche-trials.com (in the EU) or www.clinicaltrials.gov (in the United States).

Reference

i Korn EL, et al. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 2008;26(4):527-34.