OREANDA-NEWS.  February 20, 2012. Plexxikon Inc., a member of Daiichi Sankyo Group, today announced that the European Commission has approved Zelboraf® (vemurafenib) for the monotherapy treatment of adult patients with BRAFV600 mutation-positive unresectable or metastatic melanoma.  The cobas 4800 BRAF V600 Mutation Test, a companion diagnostic used to identify patients with the BRAF mutation, is CE marked and commercially available in Europe.  Zelboraf is designed to selectively inhibit the BRAF mutation that occurs in about half of all cases of melanoma.

Zelboraf and its companion diagnostic have already been approved in the United States, Switzerland, Israel, Brazil, New Zealand and Canada. In the United States, Zelboraf is being co-promoted by Daiichi Sankyo, Inc. and Genentech, a member of the Roche Group.  Roche promotes Zelboraf outside of the United States.

“The approval of Zelboraf by the European Commission marks a significant advancement for European patients with metastatic melanoma who historically have had very limited treatment options,” said K. Peter Hirth, Ph.D., chief executive officer of Plexxikon.  “We are very pleased that our strategy to co-develop Zelboraf along with a companion diagnostic helped accelerate the availability of this personalized medicine for these patients.”

BRIM3

BRIM3, a global, randomized, open-label, controlled, multicenter, Phase 3 study, compared Zelboraf to dacarbazine (chemotherapy), in 675 patients with previously untreated BRAFV600E mutation-positive, unresectable (inoperable) or metastatic melanoma.  The endpoints for BRIM3 were overall survival (OS) and investigator-assessed progression-free survival (PFS).  Other endpoints included confirmed investigator-assessed overall response rate.

In January 2011, the data safety monitoring board for BRIM3 recommended termination of the BRIM3 study due to compelling efficacy data, and further recommended that study patients receiving chemotherapy have the option to cross over to the vemurafenib treatment arm.


・The pre-specified interim analysis of BRIM3 showed the risk of death was reduced by 63 percent for patients 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 chemotherapy treatment arm to the Zelboraf treatment arm, Zelboraf significantly improved survival by providing a median overall survival of 13.2 months compared to 9.6 months for those who received chemotherapy.  Historically, patients with metastatic melanoma have had a median survival of six to 10 months.  This analysis showed the risk of death was reduced by 38 percent for patients who received Zelboraf compared to those who received chemotherapy (hazard ratio [HR]=0.62, p<0.0001).

・At 12 months, 55% of patients who received Zelboraf were alive, as compared to 43% of patients who received chemotherapy.  

In the single arm BRIM2 study of previously treated patients, Zelboraf treatment also showed a survival benefit compared to historical control data.  These data are expected to publish shortly.

Marketing authorization submissions for Zelboraf are currently under review by health authorities in Australia, India, Mexico and other countries worldwide.

Important Safety Information about Zelboraf (vemurafenib)

This information does not take the place of the patient talking to his or her doctor about their medical condition or their treatment with Zelboraf.

Zelboraf is a prescription medicine used to treat a type of skin cancer called melanoma that has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal “BRAF” gene.

Zelboraf may cause a type of skin cancer called cutaneous squamous cell carcinoma (cuSCC), that usually does not spread to other parts of the body.  Patients should check their skin and tell their doctor about skin changes including a new wart, a skin sore or reddish bump that bleeds or does not heal, or a mole that changes size or color.

While taking Zelboraf, patients should avoid going out in the sun.  When patients go outside, they should wear clothes that protect their skin, including head, face, hands, arms and legs.  They should use lip balm and a broad-spectrum UVA/UVB sunscreen with SPF 30 or higher.
 

Possible serious side effects of Zelboraf include severe allergic reactions; severe skin reactions; changes in the electrical activity of the heart called QT prolongation, which can potentially be life-threatening; abnormal liver function tests; eye problems; or new melanoma lesions.

Common side effects of Zelboraf include joint pain, rash, hair loss, tiredness, sunburn or sun sensitivity, nausea, itching or warts.

These are not all of the possible side effects of Zelboraf.  Patients must tell their doctor if they have any side effect that bothers them or does not go away.  For more information about side effects, patients should ask their doctor or pharmacist.

 Patients should call their doctor for medical advice about any side effects.  Patients or their caregivers are encouraged to report negative side effects of prescription drugs to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.  They may also report side effects to Genentech at 1-888-835-2555.