The FDA's Stunning, Dangerous Decision

Kidney cancer patients lose with a recent vote preventing access to a promising new treatment drug.

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Dena Battle is a lobbyist in Washington, DC. Her husband Chris Battle is a stage 4 kidney cancer patient. Together, they write the blog They both spoke in favor of Tivozanib approval before the Oncological Drug Advisory Committee meeting on May 2.

Last week the FDA's Oncological Drug Advisory Committee, in a stunning 13 to 1 vote shot down Aveo's new renal cell carcinoma drug Tivozanib. The sole vote in favor of the drug was the patient representative. Sadly, it's the patients who are the biggest losers in this fiasco.

The emotional aspect for patients is devastating – after all, there are many patients who are currently successfully fighting cancer with this drug in clinical trials and many more who were hoping to get access to it soon with the FDA's approval. Current patients could lose access and new patients' hopes have been dashed.

There are, however, broader implications that will likely result in significant unintended consequences that will be costly to any orphan – which is to say, rare – cancers like kidney cancer. AVEO, the manufacturer of Tivozanib, set up a clinical trial to compare the efficacy of its drug to the already approved drug Sorafenib. The primary reason the Advisory Committee cited for denying Tivozanib was that it didn't outperform Bayer's Sorafenib for overall survival benefit – meaning patients taking Tivozanib during the trial didn't live longer than those taking Sorafenib.

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Seems simple enough, right? Who wants to prescribe a drug that doesn't give patients a survival benefit? Indeed, that's what most of the doctors said when they explained their vote.

Of course, it's never that simple though.

Aveo, to their credit, designed a more compassionate study that allowed patients who were receiving the drug Sorafenib to "cross over" to the Tivozanib arm if they couldn't tolerate the drug or if their disease progressed. No shock to kidney cancer patients here – nearly 70 percent of patients crossed over to Tivo. Why isn't that a shock? Experienced patients know that Sorafenib is one of the toughest drugs out there. Side-effect wise, few patients are able to tolerate it for a long time. I'm not going to go into gory detail, but explosive diarrhea is a common complaint. Another major problem is hand/foot syndrome – where some patients' feet are so sore they are unable to walk. Few doctors prescribe Sorafenib anymore until other options have been exhausted. It's simply too toxic and there are other better drugs available.

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No good deed goes unpunished though – in a bizarre twist, Aveo's clinical trial trial design skewed the data. Patients who first received Sorafenib and then switched to Tivozanib lived longer. Tivozanib still outshined Sorafenib in progression free survival – the amount of time it took before the disease started progressing again – by an impressive three months. In fact, Tivozanib had some of the highest progression free survival data ever recorded, surpassing the other currently available drugs – providing disease control for 12.7 months. That's even more significant because progression free survival was the primary endpoint of the study ... until the FDA changed the rules and focused on overall survival rather than progression free survival.

Despite Tivozanib's impressive results, the Advisory Committee threw out the progression free survival data altogether and only looked at overall survival data. The committee seemed so determined to reject the drug that they barely let the renal cell doctors respond to their questions. Like lawyers who were trying to slide in a question without getting overruled, they asked and then quickly withdrew their questions – ushering doctors back to their seats before they could comment.

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Their decision will have a chilling effect both on future research and on clinical trial design. Given the overwhelming solidarity of the committee's vote, every major pharmaceutical company has to be asking themselves: Why would we allow crossover in our trial design? The result will be trials geared only toward data collection with less regard to patient's health – or more likely more trials conducted completely outside the U.S. – exactly what we've been opposing in the patient community.

Corrected on 5/14/13: An earlier version of this post had an incorrect byline. It was written solely by Dena Battle.