Washington Editor

WASHINGTON – Recognizing what's at stake, a Senate committee is preparing the ground for PDUFA V, even though the FDA won't submit the next five-year drug user fee plan until January.

"The FDA is close to a tipping point," Sen. Michael Enzi (R-Wyo.), ranking member of the Senate Health, Education, Labor and Pensions (HELP) Committee, said in opening remarks Thursday at a committee hearing on drug and medical device user fees.

He noted the FDA has been placed on a high-risk list of government agencies because it is being overwhelmed by increasing responsibilities and limited resources.

In shifting staff resources to ensure the timely implementation of safety provisions mandated by the FDA Amendments Act (FDAAA), passed in conjunction with PDUFA IV in 2007, the agency slipped in its performance goals for timely approvals of new drugs and biologics. (See BioWorld Today, July 11, 2011.)

The FDA relies on user fees to fund drug approval activities and implement the safety requirements. If PDUFA is allowed to expire Sept. 30, 2012, the agency's Center for Drug Evaluation and Research would have to lay off 60 percent of its staff, Enzi said.

Despite that warning, some committee members indicated there's some ground to be covered before they're willing to sign off on the new user fee/performance agreements that are negotiated with industry.

"I'm somewhat bewildered that industry was willing to sit down" and negotiate with the FDA, Sen. Richard Burr (R-N.C.) told FDA Commissioner Margaret Hamburg at the hearing. Given the time to approval and the agency's aversion to risk, industry is not getting its money's worth, he said, adding that he is disturbed by the idea of "give us more money, and we'll do a better job."

Burr insisted that the next PDUFA must have measurements to ensure the agency is truly meeting its performance goals on approval times. He also is asking the Government Accountability Office for a review of those goals.

Hamburg defended the agency's record under PDUFA, saying its drug approval times have improved considerably since PDUFA was first enacted in 1992. The agency is now approving 68 percent of priority new molecular entities in the first cycle as compared with 46 percent 20 years ago. And the length of the approval phase for a new drug has been cut by 60 percent – from an average of two years in 1992 to a little more than one year today.

Approval time, especially when measured in "FDA days," is not what's important to patients, Burr said. They care about the actual time to market, which is being affected by what's perceived as a growing aversion to risk at the FDA. When the agency requests more data from a sponsor, it stops the clock until the data are submitted. Thus, what the FDA reports as 30 days could actually be a lot longer.

Burr said he would support PDUFA V if the performance goals were measured by real calendar days instead of FDA days.

Sen. Kay Hagan (D-N.C.) raised another problem – complete response letters. Once the FDA issues the letter, it no longer has any time frame to respond to the sponsor, which gets limited feedback on what it needs to do to get the product approved, she said.

Several senators voiced concern about finding the balance between regulation and innovation. Burr stressed the need for an approach that doesn't create barriers to new drugs to treat conditions such as diabetes or obesity.

Sen. Michael Bennet (D-Colo.) said without an appropriate balance, the U.S. is in danger of losing its competitive advantage.

Hamburg acknowledged the challenges facing the FDA and stressed the importance of PDUFA. User fees accounted for about 62 percent, or roughly $568 million, of the $931.8 million allocated for drug reviews and support activities in fiscal 2010, she testified.

The 2012 drug user fees, which were to be published in the Federal Register Monday, are expected to generate more than $702.1 million. Effective Oct. 1, the filing fee for new drug applications requiring clinical data will be more than $1.8 million. Fees for applications that don't require clinical data or supplements will be $920,750. Establishment registration fees will be $520, 100, and product listing fees are $98,970.

If approved by Congress, PDUFA V would generate about $712.8 million in drug user fees in fiscal 2013, based on a 6 percent increase over the fiscal 2012 user fees, Hamburg told the HELP Committee.

Avastin Garners Support on Comment Board

The FDA's proposal to withdraw its approval for Genentech Inc.'s Avastin as a breast cancer treatment has generated a lot of comment, but whether the input from patients and lawmakers is enough to change the agency's intent remains to be seen.

The FDA extended the comment period following a June hearing in which the agency's Oncologic Drugs Advisory Committee (ODAC) concluded that Genentech's AVADO and RIBBON1 trials failed to verify the clinical benefit of Avastin (bevacizumab) for metastatic breast cancer, that the available evidence on Avastin failed to demonstrate effectiveness for metastatic breast cancer and that Avastin has not demonstrated a clinical benefit that justifies the risks associated with its use in the indication. (See BioWorld Today, June 30, 2011.)

More than 450 comments and documents had been posted by time the extended comment period ended Thursday. Many of those comments came from patients citing anecdotal information contradicting ODAC's findings.

Christi Turnage, for instance, was diagnosed with breast cancer in 2006 and has had no progression since she was put on Avastin three years ago. The registered nurse said her experience may not be the norm of what was found in clinical trials, but such cases exist. "We exist," she said.

"The definition of a clinical benefit is a personal question that each patient needs to answer on their own," she added. "It should not be decided by others."

Also included in the comment docket are several responses from the FDA to congressmen who had inquired about the differences between the U.S. approval and Avastin's approval in Europe. Avastin was granted full approval for the breast cancer indication in Europe, so no confirmatory trials were needed there, the FDA said in its form letter response.

Now that the comment period has ended, it is up to FDA Commissioner Margaret Hamburg to review the record and decide whether the indication should be withdrawn.