Over the past several years, Pfizer (NYSE: PFE ) has taken bold steps to streamline its operations and improve profitability after a wave of patent expirations. Focusing on the company's emerging oncology segment seemed like a great plan, until the recent failures of a lung cancer candidate with high expectations.
Dacomitinib is an epidermal growth factor receptor tyrosine kinase inhibitor, one of many tumor fighting drugs more commonly referred to as EGFR inhibitors. This experimental drug was expected to eventually put its non-small cell lung cancer (NCLSC) competitors on the ropes. Unlike Tarceva from Roche (NASDAQOTH: RHHBY ) and Iressa from partners AstraZeneca (NYSE: AZN ) and Teva (NYSE: TEVA ) , Pfizer's unique therapy is irreversible and acts on multiple receptor types. Let's take a look at just how far this will set back the restructured pharma giant.
Combined, Tarceva and and Iressa racked up about $2 billion worldwide in 2012. Dacomitinib wasn't expected to be a blockbuster on the scale of a drug like Lipitor, which was Pfizer's most successful drug and formerly the top-selling drug in the world. However, dacomitinib's failed trials would sting much less if they occurred during earlier stages of development.
What went wrong
Not long ago, dacomitinib had the competition shaking in their boots. Results from a 188 patient trial released at the end of 2012 showed significantly stronger responses when compared to Tarceva. The problem with the drug wasn't safety or response rates, but long term survival. In the ARCHER 1009 trial, about 800 patients were given either Tarceva or dacomitinib. After 10 months the patients given dacomitinib did not show significant improvement in progression-free survival compared to patients that received Tarceva.
In the BR.26 trial, advanced lung cancer patients that had been treated previously with either Tarceva or Iressa, were given placebo or dacomitinib. At three and a half years, the overall survival rate of patients given dacomitinib was not significantly higher than those given placebo.
As awful as these failures seem, they do not necessarily seal dacomitinib's fate. It is possible that patients in certain subsets responded more strongly to the therapy. Pfizer hasn't disclosed every detail yet. There is still a possibility that the therapy is more effective for groups of patients that don't respond to available drugs.
To get a sense of how Pfizer can salvage something from its dacomitinib program, it helps to understand some history behind EGFR inhibitors. AstraZeneca and Teva's Iressa won an accelerated approval for second-line treatment of NCLSC way back in 2003. Because of the unmet need at the time, the FDA approved its use based on tumor response rates. Underwhelming long-term survival rates in follow-up studies later resulted in a limited indication.
In 2004, Roche's Tarceva won approval for the same indication as Iressa. But Tarceva won the old fashioned way, with improved survival data compared to existing treatments.
Pfizer hasn't released all the data yet, so it is difficult to make direct comparisons with existing therapies. The important takeaway is that dacomitinib didn't fail because it's not effective at all, but rather because it wasn't better at lengthening survival rates among a wide range of patients.
In May of last year, Tarceva won an expanded approval for first-line treatment of NCLSC in patients with specific mutations. The indication was approved together with Roche's companion diagnostic that screens for those mutations.
More recently, Boehringer Ingelheim scored a similar NCLSC approval with Gilotrif and a companion diagnostic from Qiagen. The FDA has made it clear that it supports personalized cancer treatments for difficult to treat lung cancers and beyond.
Dacomitinib might not win an approval for the entire range of mutations it was intended to treat. But odds are decent that within the hundreds of patients treated in late stage trials, there's a group with unmet need that showed a significant response.
Complete results from the failed trials should be released later this year. Also, a third phase 3 trial for first-line treatment of NCLSC patients with EGFR mutations is expected next year. It's a long shot, but Pfizer's latest trial failures might not be a total loss after all.