Clinical Development

Onyx is advancing a robust pipeline of innovative investigational therapies targeting several molecular pathways in cancers, with the goal of extending and enhancing the lives of patients.

Nexavar^® (sorafenib) Tablets

The goal of the development program for Nexavar^® (sorafenib) tablets, an oral anticancer drug currently approved to treat two cancers, is to further evaluate the drug's efficacy, safety, and potential to be combined with other anti-cancer agents in the treatment of a range of cancers.

Sorafenib is currently being evaluated in late-stage Phase 3 trials to determine its potential in non-small cell lung cancer, thyroid cancer, breast cancer and as an add-on treatment for liver and kidney cancer following surgery.  In addition, there are several studies evaluating sorafenib in combination with localized treatments, such as transarterial chemoembolization (TACE), for the potential treatment of liver cancer.  TACE therapy involves local administration of highly concentrated chemotherapy at the location of the tumor and embolization is a non-surgical procedure that blocks blood flow to the tumor.  Sorafenib is also being studied in combination with other anti-cancer therapies, also for the potential treatment of liver cancer.  Sorafenib is developed and marketed in collaboration with Bayer HealthCare Pharmaceuticals, Inc.

Carfilzomib

Onyx is also developing carfilzomib for the potential treatment of multiple myeloma, a deadly blood cancer.  Our New Drug Application (NDA) for carfilzomib is currently under review by the FDA under the accelerated approval process for the potential treatment of patients with relapsed and refractory multiple myeloma.  The filing was primarily based on the positive results from a Phase 2b single-agent study, known as the 003-A1 trial, in patients with relapsed and refractory multiple myeloma.

Carfilzomib is also being evaluated in a Phase 1b/2 study in patients with solid tumors.

Earlier Stage Pipeline

In addition to carfilzomib, our proteasome inhibitor program includes oprozomib (formerly ONX 0912), an oral proteasome inhibitor currently in Phase 1b/2 clinical testing.  It also includes ONX 0914, an immunoproteasome inhibitor with preclinical activity in models of autoimmune disorders.

PD 0332991, an oral small molecule cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, resulting from a collaboration with Pfizer, is currently in Phase 2 clinical development for hematologic malignancies and solid tumors.  Onyx would receive milestone and royalty payments on any worldwide sales.

Important Safety Considerations

• Nexavar in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer
• Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential are advised to avoid becoming pregnant and female patients should also be advised against breastfeeding while receiving Nexavar
• Cardiac ischemia and/or myocardial infarction may occur. Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischemia and/or myocardial infarction
• Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking Nexavar
• Uncommon but serious adverse reactions, including keratoacanthomas/squamous cell cancer of the skin and Stevens-Johnson Syndrome, have been reported in clinical trials
• An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider discontinuation of Nexavar
• Hypertension may occur early in the course of treatment. Monitor blood pressure weekly during the first 6 weeks and periodically thereafter and treat, as required
• Hand-foot skin reaction and rash are common and management may include topical therapies for symptomatic relief. In cases of any severe or persistent adverse reactions, temporary treatment interruption, dose modification, or permanent discontinuation of Nexavar should be considered. Temporary interruption of Nexavar therapy is recommended in patients undergoing major surgical procedures
• Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Caution is recommended when administering Nexavar with compounds that are metabolized/eliminated predominantly by the UGT1A9 pathway, UGT1A1 pathway (eg, irinotecan), doxorubicin, docetaxel, fluorouracil, and substrates of CYP2B6 and CYP2C8, and CYP3A4 inducers. Concomitant use of carboplatin and paclitaxel with sorafenib resulted in an increase in paclitaxel exposure and an increase in Nexavar exposure. Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time, INR, or clinical bleeding episodes. Nexavar exposure decreases when coadministered with oral neomycin. Effects of other antibiotics on Nexavar pharmacokinetics have not been studied
• Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in unresectable HCC, respectively, were: diarrhea (55% vs 25%), fatigue (46% vs 45%), abdominal pain (31% vs 26%), weight loss (30% vs 10%), anorexia (29% vs 18%), nausea (24% vs 20%), and hand-foot skin reaction (21% vs 3%). Grade 3/4 adverse reactions were 45% vs 32%
• During postapproval use of Nexavar, the following adverse drug reactions have been identified: angioedema and drug-induced hepatitis, including reports of hepatic failure and death