7-25-2013 Inside Health Policy - Stakeholders, FDA Working On 'Breakthrough' Dx Proposal | Friends of Cancer Research

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7-25-2013 Inside Health Policy - Stakeholders, FDA Working On 'Breakthrough' Dx Proposal

Inside Health Policy - Stakeholders, FDA Working on 'Breakthrough' Dx Proposal

July 25, 2013

By Nanci Bompey

Friends of Cancer Research is working with FDA and other groups on a proposal for accelerating development of diagnostics used in conjunction with drugs granted the new breakthrough therapy designation, and FDA could also put out guidance on the topic. Stakeholders said the breakthrough drug approval pathway represents a new way of interacting with FDA, but questions remain about manufacturing, testing, inspections, international harmonization, resources and payment, including whether insurers will require cost-benefit analyses based on trials with definitive endpoints and large numbers of patients.

The breakthrough therapy pathway, created by the FDA Safety and Innovation Act, is intended to speed up development of treatments for serious or life-threatening diseases that show potential in early clinical trials. FDA has granted 24 designations to date, with 17 made public so far, but has yet to address diagnostics used in conjunction with breakthrough drugs.

Friends of Cancer Research, which spearheaded inclusion of the breakthrough pathway in FDASIA, hopes to roll out a proposal on the issue during a public meeting Sept. 6, said Ellen Sigal, chair and founder of Friends of Cancer Research. The possible proposal would address ways to speed up the development and regulatory process for companion diagnostics used in conjunction with breakthrough drug therapies.

The comments came during a congressional briefing hosted by Friends of Cancer Research Wednesday (July 24).

Sigal said it does not appear that the proposal will require additional legislation. Janet Woodcock, head of FDA's drug center, said the agency could also address diagnostics and other breakthrough-related policy issues like subsets of patients in future guidance.

Officials from companies that received some of the earliest designations said the breakthrough pathway represents a more interactive, collaborative way of communicating with FDA about all aspects of the drug development process.

“It's a different kind of conversation,” said Jeffrey Leiden, CEO of Vertex Pharmaceuticals, which has nabbed two breakthrough designations. “It's a different way of interacting with FDA.”

Jay Siegel, head of global regulatory affairs at Johnson & Johnson, credited FDA's implementation of the new pathway with its initial success. The company has received four designations for two products it is developing and Siegel said the pathway could accelerate the approval timeline by up to two years for one drug. Siegel said active engagement by FDA leadership makes it easier to deal with issues like scaling up manufacturing or validating assays. Further, FDA has been proactive in the process, he said.

Some stakeholders expressed concern, however, that the agency may not have enough resources. Sigal said the group envisioned that FDA would grant a handful of designations each year, but the high number of designations means the agency may need additional resources. Woodcock said the agency tries to manage its entire portfolio so it is not really a trade off between resources for “breakthrough” drugs and other products. “We just have to do the best we can with the resources we have,” she said.

FDA also has expressed concern that companies will not be able to scale-up their manufacturing to deal with the accelerated development process under the new pathway.

Siegel said manufacturing issues will need to be addressed with advanced planning to keep it from being the “rate limiting step” in the process. Siegel said, for example, FDA could be flexible in allowing validation criteria for testing a batch to be defined after producing a final batch because timelines have been accelerated. Siegel said the agency could also be more flexible in allowing, for example, less complete stability data at approval with plans to deal with it post-approval. Siegel said FDA has also had a difficult time quickly scheduling foreign inspections, and he anticipates there will be other issues that companies and FDA will need to address.

“Every time you accelerate one thing, something else becomes the rate limiting step,” he said.

Leiden said that these manufacturing challenges could, however, present opportunities to update and streamline the process. Woodcock said breakthrough could be an opportunity to motivate FDA and stakeholders to move forward with the agency's drug quality overhaul that it has been rolling out.

Another challenge posed by the new pathway is differences in the type of data FDA is asking for and the data required by foreign payers and regulators, Siegel said. For example, FDA could tell companies to get rid of a control group while European regulators might still require the control group.

However, Siegel said he is “optimistic and hopeful” that foreign regulators will want to catch up with FDA and the company already has preliminary reports that some foreign authorities are talking about speeding up development timelines in line with FDA's breakthrough pathway.

Siegel said the success of the breakthrough pathway could also ride on market access to the products. He said insurance companies may require cost-benefit analyses based on trials with definitive endpoints and large numbers of patients, which breakthrough drugs may not have.

“That is really going to require some attention: how do you bring payers on board,” he said.