While all cancers display uninterrupted cell proliferation, their heterogeneity often makes them difficult to treat. Given these characteristics, Plexxikon is pursuing a number of drug targets for the treatment of different cancers.
Melanoma and BRAF Mutant Cancer
Zelboraf™ (vemurafenib), formerly known as PLX4032, is Plexxikon's lead program in its expanding oncology franchise. This drug is an oral, small molecule, kinase inhibitor that targets the BRAF mutation, occurring in about half of all cases of melanomas. Zelboraf was approved by the FDA for the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test. Zelboraf is not recommended for use in melanoma patients who lack the BRAF V600E mutation. A companion diagnostic which determines a patient’s eligibility for Zelboraf treatment, the cobas 4800 BRAF V600 Mutation Test, was also approved by FDA at the same time. Marketing approval applications for Zelboraf are pending in Europe and a number of other countries. Zelboraf is being co-developed with Plexxikon's partner, Roche. Please see important information about Zelboraf below.*
Data from clinical studies of Zelboraf have been published in the New England Journal of Medicine in August 2010 and June 2011, as well as in Nature in September 2010.
Other Zelboraf trials are under way or planned, including combination trials with other investigational agents. See www.clinicaltrials.gov for further information about these trials.
Osteolytic Metastatic Disease
Plexxikon has developed a portfolio of novel, oral inhibitors that selectively inhibit two key kinase targets, FMS and Kit. These drug candidates are designed to treat diseases primarily driven by osteoclasts, macrophages and mast cells, which play key roles in certain cancers and inflammatory diseases.
PLX3397 is Plexxikon's lead compound in its FMS portfolio, and is currently in Phase 1 clinical trials to test the initial safety, tolerability and pharmacokinetics in cancer patients. PLX3397 is a highly selective kinase inhibitor that down-modulates macrophages, osteoclasts and mast cells, as well as certain tumor cells that promote tumor growth and metastases to the bone.
Preclinical data have shown PLX3397’s antitumor effects, including a decrease in circulating tumor burden, delay of tumor metastases and inhibition of tumor growth. Pending completion of the Phase 1 study, the company is planning to explore PLX3397 in specific cancers, including metastatic breast cancer.
* Important Safety Information for Zelboraf
This information does not take the place of the patient talking to their 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 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 may report side effects to the FDA at 1-800-FDA-1088. They may also report side effects to Genentech at 1-888-835-2555.
Patients should read the Zelboraf full Prescribing Information and Medication Guide for additional important safety information at http://www.zelboraf.com.