CBI Scene Blog

A Cautionary Tale as You Prepare for an FDA Advisory Committee Meeting

Posted by Scott Wallask on Sep 10, 2013 9:36:00 AM

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Imagine your pharmaceutical company has a promising drug that seems to be on a solid pace heading toward FDA approval. Your investors are cheering you on, and sick patients who want the drug are holding their breath as you head towards the finish line.

But then, instead of winning the race, you teeter off course and find yourself face down in the weeds.

Aveo Oncology ran into a similar situation that certainly would make other pharma companies cringe. According to a recent Boston Globe article, an FDA advisory committee vote derailed Aveo’s big hopes for its new kidney cancer drug called tivozanib.

The FDA Oncologic Drugs Advisory Committee voted 13-1 against the firm’s kidney cancer medicine in May. The FDA followed up by formally rejecting the drug submission. According to transcripts of the meeting, the government was unimpressed with several aspects of Aveo’s research, including the following:

  • The lack of a double-blind trial
  • The fact that 88 percent of trial participants were from Eastern Europe and not countries served by Western-based medicine
  • Results that indicated the survival rate of people using tivozanib was worse than the rate of those taking a another cancer drug used as a comparison in some of the trials

 “I couldn't imagine sitting down and telling a patient that I was going to put them on a drug where the clinical trial showed that it would actually shorten their survival,” said Louis Diehl, MD, a member of the committee, according to a transcript of the meeting.

Now trying to brush itself off and get back on its feet, Aveo continues to push forward with other cancer drug research. However, it is doing so at a price: Following the FDA’s rejection, the company laid off 140 employees, according to a somber press release about the company’s second quarter financial results for 2013. And Aveo also faces lawsuits from investors who feel the company was not up front about its claims with tivozanib, an allegation the company takes umbrage with, the Globe reported.

So, What Happened?

The Globe detailed the history of tivozanib and the progress of the associated clinical trials. Aveo spent $300 million to develop the drug.

A key question the Globe brought up: Why did Aveo allegedly not appropriately answer FDA concerns about tivozanib’s effectiveness when asked before the meeting?

Transcripts of the meeting indicate Aveo representatives believed those answers perhaps lay beyond tivozanib.

“Our review of the fatal adverse events and of the tivozanib serum exposure analyses do not provide evidence that the overall survival trend is due to increased toxicity from tivozanib,” Anna Berkenbilt, MD, head of clinical research at Aveo, told committee members.

Tips to Better Navigate Advisory Committees

I can’t help but think of Aveo as I wrap up research calls preparing for CBI’s 5th Annual Effective Preparation for FDA Advisory Committee Meetings conference, which takes place February 4-5, 2014, in Washington, DC. Several folks have mentioned the need for presenters to not get bogged down with what they want to tell an advisory committee. Instead, companies need to find out what the FDA wants to know from them.

That sounds like quick sand to me — no one can fault pharma company representatives for wanting to stay on script and focus on “their story.” After all, they spend months and millions of bucks preparing for a committee presentation.

The FDA noted four aspects of the Aveo clinical trials that it had problems with. Regardless of your feelings on whether tivozanib should be approved, the FDA’s suggestions are good points to remember for all pharma companies submitting drug applications:

    • Although the FDA accepts progression-free survival (i.e., how long after treatment a patient lives with cancer but the cancer does not get worse) as the primary endpoint for certain diseases, overall survival remains the ultimate efficacy and safety endpoint.
    • Do not conduct after-study analyses in non-randomized patient populations. The FDA wants to see well-controlled studies. 
    • Avoid presenting inconsistent progression-free survival and overall survival results because such data may be inconclusive when determining the risk-and-benefit assessment needed for a drug approval.
    • For clinical trials conducted outside the United States, be sure the trials and post-study treatments reflect a U.S. standard of care.

Presenting challenging data to the FDA can result in damage beyond a company’s business plan. In the case of Aveo, proponents outside of the company believed the drug was effective.

“During the 15 months that I have been taking this drug, there has been an overall 46 percent decrease in lesions, with very little side effects,” kidney cancer patient Richard Bruno told the committee, according to the meeting transcript. “This drug has given me hope that I never had before.”

Now, after the FDA’s ruling, kidney cancer patients once hopeful of using tivozanib have to look elsewhere, which must be heartbreaking.

“We're all aware that people want new options for the treatment of cancer,” said Richard Pazdur, MD, director of the FDA’s Office of Hematology & Oncology Products, according to the transcript. “But that enthusiasm should not be just a wild enthusiasm without looking at the data.” 

There wasn’t a plan B for Aveo employees who lost their jobs after tivozanib tanked before the advisory committee. Lots of pharma workers are in the same situation, plying their trade at companies that bank on one key product’s approval.

But you won’t find that stark fact in any of the committee meeting minutes. What’s next for those workers when a drug gets sidelined?

Follow Scott on Twitter @Scott_CBI

 

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(Image courtesy via Chris Potter)

Topics: Compliance