BIO 2012 – PDUFA V earns praise from industry


Expanding accelerated approvals to areas other than cancer and HIV treatments and incorporating patient views into the FDA’s risk-benefit judgements are the two most important advances to drug regulation under the reauthorisation of PDUFA expected to come before US President Barack Obama shortly, experts speaking at the BIO international conference said.

While pharmaceutical and biotech manufacturers might be disappointed that the document will extend the time it will take many candidates to achieve an approval once the FDA has begun review, it is also expected to allow a shortened clinical development time for many more compounds addressing an unmet medical need. Incorporating “structured risk-benefit” discussions into drug reviews, meanwhile, could allow regulators to justify approval of products with greater safety concerns based on patient input.

Accelerated review

The PDUFA extension is now part of a larger package encompassing user fees for medical devices, generics and biosimilars that was approved by the House earlier this week and awaits Senate action. Final passage of the fifth renewal of the Prescription Drug User Fee Act is expected to be relatively non-controversial as the legislation has been carefully negotiated over at least two years (PDUFA V nears final act, May 31, 2012).

Given the political ramifications expected from a long-awaited Supreme Court decision on the US healthcare reform law, there is likely a desire in the Senate to vote the FDA user fee programme through before the legislation can be caught up (BIO 2012 – Industry fears turbulence from US healthcare reform ruling, June 20, 2012). Thus it is expected that the legislation will be sent to Mr Obama for his signature in the coming days.

Experts speaking at the BIO meeting said they were looking forward to enhancement of accelerated approval authority, which allows approval based on a surrogate endpoint in serious diseases for which no treatment exists. In cancer and HIV accelerated approvals have been based on tumour shrinkage or viral load respectively, as those surrogate endpoints were believed to extend surivival.

“There has been a lack of clarity about how it can be used outside those areas,” said Jonathan Leff, managing director for healthcare at the private equity firm Warburg Pincus. “In cancer and HIV, it’s really transformed the landscape of those diseases."

The details of the diseases that need new drugs to be sped to market will need to be defined, along with the surrogate endpoints, but having specific legal authority is a step forward, Mr Leff said. In three to five years, he said, “I fully expect to see a significant number of accelerated approvals in areas we haven’t seen before. If we don’t, we should be disappointed.”

Patient input

While only one paragraph in the PDUFA package discusses the “structured risk-benefit” process that will be initiated following passage, this is outlined more fully in technical documents that emerged from public consultations.

Mr Leff notes that the inclusion of this in the legislation will help the agency justify its actions to Congress should safety concerns materialise from any drug approved following application of a structured risk-benefit analysis. “I hope that one paragraph elevates the conversation about what drugs do and what regulators can do to assess risk,” he said.

The provision calls on the FDA to nominate specific conditions with a need for new treatments and to consider patients' views as to the acceptable risks given disease severity. A draft five-year plan for implementing the process will be published in early 2013.

As far as the developments in the new PDUFA are concerned, “it’s probably the most important if we really get it right”, said Peter Greenleaf, president of AstraZeneca’s MedImmune unit.

On the extension of review time – triggered by the establishment of a new pre-submission meeting two months before formal delivery of a drug application – Mr Greenleaf said this was not a preferable outcome. However, he noted that if improved communication between regulators and pharma companies could result in fewer rejections it would be positive for the industry.

“We know that more communication is better, and now we’re going to institutionalise it,” FDA Commissioner Margaret Hamburg said of the extended timeline. “Now we are going to add more people and operationalise the new liaison staff. The goal is to speed the review process and achieve more first-cycle approvals, and we think we can do this."

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