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Try as they might, Bayer (OTCPK:BAYRY) and Onyx Pharmaceuticals (NASDAQ:ONXX) have been struggling for some time to prove that Nexavar has a role beyond liver and kidney cancer. Therefore news that the drug has failed in a second phase III lung cancer study is hardly encouraging.

Despite these two failed trials, executives at Onyx Pharmaceuticals struck an upbeat note on a conference call Monday, pointing to upcoming data in breast cancer and another lung cancer trial in a different setting, and expressing confidence that additional tumor types are within the kinase inhibitor’s grasp. However, with Onyx having invested heavily in this quest, at the expense of profitability, good news is needed to restore some flagging confidence (Onyx needs to find Nexavar growth as another quarter disappoints, April 30, 2010).

Failure to prolong

The results released today were from a study called Nexus, which pitted Nexavar in combination with gemcitabine and cisplatin against the two chemotherapy agents alone, in patients newly diagnosed with non-squamous, non-small cell lung cancer.

The addition of Nexavar failed to prolong overall survival, the primary endpoint, although progression free survival was significantly extended. Although it has hard to draw firm conclusions without any hard data, which is being held back for a medical conference, it is hard to classify the trial as anything but a failure with the primary endpoint missed.

Another similar trial called Escape, but which used a different chemotherapy regimen, was ended in early 2008 after an interim analysis concluded survival would not be prolonged and more deaths were seen in patients with squamous lung cancer; this prompted the Nexus study to be amended to include only non-squamous histologies.

Biomarkers

Despite this set back, Onyx management said they are looking forward to results from another phase III trial called Mission. This is enrolling around 850 patients with advanced relapsed or refractory non-squamous NSCLC who have failed two or three previous treatments. Nexavar or placebo will be administered as a monotherapy, plus best supportive care, and the primary endpoint is overall survival.

A big priority of this trial is the collection of biomarkers, in an attempt to find out whether responders to Nexavar can be identified. Encouraging signals from a trial called Battle, presented at Asco, are allowing the company to keep the faith in lung cancer.

The Battle program is a series of phase II studies being carried out by the MD Anderson Cancer Center, seeking to prospectively evaluate biomarkers in an attempt to guide treatment selection in patients with advanced NSCLC. After one chemotherapy round, researchers are biopsying tumors to determine molecular features such as epidermal growth factor receptor and KRAS mutations. Patients are then randomized to receive Nexavar, Roche’s (OTCQX:RHHBY) Tarceva, AstraZeneca’s (NYSE:AZN) Zactima or Tarceva plus bexarotene, and the design allows future patients to be matched with the therapy that appears to have the biggest impact on their tumor type.

Results from the Nexavar subset presented at Asco last week revealed that disease response rates at 8 weeks was improved in patients with KRAS mutations, while those who had an EGFR mutation did worse.

Today, Onyx management stressed that collecting biomarkers is a big emphasis in the Mission study. Clearly, the company hopes that even if the trial is not a runaway success in all patients, a subset can be identified. With other work going on in this area that might well back up the data, a route to market is clearly in their sights.

Adding value

Mission only started last year and recruitment is still ongoing, so data is unlikely to be available until later in 2011. It is probably worth remembering that lung cancer is proving one of the hardest tumors to defeat, as the numerous clinical setbacks recently, in mid and late stage, are testament to (Therapeutic focus - Late stage set backs sharpen focus on earlier lung cancer candidates, March 31, 2010).

Still, sales by indication data from EvaluatePharma reveal that of the $1.39bn in sales that analysts are expecting from Nexavar in 2016, only 7% are from lung cancer. Therefore only success, rather than failure, in this cancer type will have a meaningful impact on forecasts.

However, the failure announced today will not be great for sentiment. Onyx shares have fallen 24% since disappointing first quarter Nexavar sales were released at the end of April and the stock touched a three-year low last week of $21.85.

With phase II breast cancer due later this year - which is being ascribed slightly more potential value than lung, 12% of the 2016 forecast – Nexavar needs to start generating definitive proof of broader utility, particularly as competition continues to increase in the cancers where marketing approval has already been won.

Source: Onyx Pharma, Bayer Have Yet to Prove Utility of Cancer Drug