Gottlieb Uses ASCO Platform To Unveil Two Pilot Programs To Speed Drug Review

US FDA commissioner outlines plans to allow partial submissions as soon as database locks and to create joint sponsor-agency review documents.

US FDA Commissioner Scott Gottlieb used the opening session of the American Society of Oncology annual meeting in Chicago on June 2 as an opportunity to deliver a message that the agency is laser-focused on improving the drug review process to speed new innovations to market.

"There are critics who think that we should hold drugs back from the market, and demand more pre-market studies emphasizing overall survival endpoints before we consider approving new treatments," he said. "I disagree. And I suspect some patients who face long odds, for who available therapy gives them a slim chance of long-term survival, might also disagree," he said.

Gottlieb backed his message up with examples of the way FDA is changing and even announced two new pilot programs the agency is implementing to speed drug review. He highlighted FDA's approval of Merck & Co. Inc.'s immunotherapy Keytruda (pembrolizumab) in May 2017 for microsatellite instability-high or mismatch repair deficient tumors as an example of where the agency is headed.

The Keytruda supplement was the first approval of a drug based on a molecularly defined cancer, rather than based on tissue origin. (Also see "Biomarker-Led Claim Is Small Step For Merck's Keytruda, Giant Leap For Cancer Indications" - Pink Sheet, 23 May, 2017.)

Genomics-based drug development is a big theme at ASCO this year as drug makers and others look increasingly to understand the molecular underpinnings of cancer and move the bar beyond the first wave of highly-targeted cancer drugs.

He talked about modernizing clinical trial eligibility criteria and conducting clinical trials in the communities where patients live to help make experimental therapies more readily available to patients, though he did not mention the new Right To Try bill signed by President Trump May 22. (Also see "US FDA Right To Try Policy: For Now, Defer Questions To Sponsors, Bill Text" - Pink Sheet, 30 May, 2018.)

Starting Review At Data Lock

The two pilot programs he announced center around efforts to improve the way FDA evaluates new applications as part of the clinical portion of the review, he said.

One program, called real-time oncology review (RTOR) is aimed at focusing submissions more squarely on the data that's most important to weigh safety and effectiveness by reducing superfluous information. The program is currently being tested in new efficacy supplements for already approved cancer drugs, but it could be expanded to new drugs and biologics if it is successful. The program is already underway and a number of sponsors have already agreed to it, he said.

Gottlieb said the new approach could free up 10% to 30% of reviewers' time and lead to more efficient reviews. 

Under the program, as soon as a sponsor locks their database and decides they want to file for FDA approval, they can start sharing the bottom-line data with FDA.

"The goal is to improve the overall quality of applications and make sure resources and review time are being focused on evaluating information that is meaningful to clinicians and patients," Gottlieb said. This will help to ensure that what is included in the application is important and that nothing critical is missing.

"The worst possible time to discover this is after an application has been filed with the agency," he said. "It delays review and adds to the time and cost of the process, including staffing burdens."

In effect, he said the program allows FDA to pre-review the data and assess it for adequacy and completeness,  after a sponsor's database is locked. The partial data package will include raw and derived data sets including safety and efficacy tables and figures, the study protocol and amendments and a draft of the package insert, he said.

F"DA will immediately start evaluating the data for its sufficiency and integrity," Gottlieb said. This will allow reviewers an opportunity to address data quality issues and provide early feedback to sponsors on how to inform key regulatory questions.

"By the time the sponsor files the application with the FDA, the agency's review team would already be very familiar with the data and the analysis," Gottlieb said. "Review teams will be in a better position to conduct a more efficient, timelier and thorough review."

Layering Onto Sponsor's Document

As part of the RTOR, FDA is also piloting a new assessment tool to streamline the administrative portion of the submission. FDA is unveiling a voluntary submission form sponsors can use to facilitate FDA's assessment of the drug application. For now, this pilot is also focused on supplemental applications. The new templated approach will use the sponsor's structured file as the basis for the review rather than FDA writing a separate analysis of the file.

"We'll use the sponsor's own submission as the document for layering in our review," he said. "Under this approach, we'll annotate the drug file with our assessment rather than create a separate document that recapitulates many of the same results," he said. 

FDA is using a similar approach in its generics office in an effort speed up ANDA reviews. (Also see "FDA Ends ANDA 'Reviews' To Streamline Approval Process" - Pink Sheet, 3 Jan, 2018.)

As NDA reviews work now, the template is divided into two parts, the applicant's part and the FDA's assessment of that position. Under the pilot, he said FDA will make notes right in the sponsor's file where it agrees or disagrees and add additional findings and analysis. The aim is to reduce the administrative burden on FDA reviewers so they can focus on the more important results and analysis.

If a drug makes it through the drug review process, the completed review will be presented at a meeting of the Oncology Drugs Advisory Committee as one single, combined background document that contains both the applicant's opinion and FDA's analysis of those positions.

In addition to the pilots mentioned by Gottlieb, FDA's oncology office is also pursuing review changes in the areas of modeling, endpoints, and real-world evidence (Also see "Immuno-Oncology’s Revolutionary Impact – On US FDA" - Pink Sheet, 21 Feb, 2018.) and has also undertaken a review pilot to assess some supplemental applications using summary data rather than the complete “raw” (Also see "FDA’s Streamlined Review Pilot Takes Flight; Second Oncology sNDA Through Process" - Pink Sheet, 1 Apr, 2015.)