ARTICLE | Regulation

Letter from the Editor

Letter from the Editor: Back to School 2021

Stretching the vision of accelerated approval

Stretching the vision of accelerated approval.

August 30, 2021 6:04 AM UTC

At some snapshots in time, one issue bubbles to the surface, demanding attention and solutions to problems that have been simmering for years.

Right now, that issue is accelerated approval.

BioCentury’s 29th Back to School project examines the future of accelerated and conditional approvals globally, and stretches the vision of what these pathways could achieve.

FDA’s accelerated approval pathway, introduced in 1992, has spawned similar schemes in Europe, Japan, China and the U.K., each of which added nuanced changes but based their pathways on the same idea — granting approval for a drug on the basis of less data than for full approval, to expedite treatments to patients with severe disease and no alternatives, on the condition that data collection will continue postmarket; if the evidence does not uphold the risk-benefit assessment, the drug or an indication can be withdrawn. 

The catalyst for the current furor was FDA’s surprising and controversial decision to grant accelerated approval to Aduhelm aducanumab-avwa, the Alzheimer’s therapy from Biogen Inc. (NASDAQ:BIIB). But the issues go far beyond Aduhelm, and far wider than the pathway in the U.S.

There are opposite perspectives on the topic, both of which hold true. Accelerated approval has been a raging success for what it’s done for the treatment of cancer. At the same time, it’s been a disappointment for almost all other major disease areas, where, outside of HIV, it has had next to no impact. Moreover, the pathway continues to stir controversy after controversy.

BioCentury’s editors have analyzed reams of data, charted the issues, and talked with stakeholders across three continents and all sectors of the industry.

The zeitgeist shows much frustration with accelerated and conditional approvals, at the same time as a deep desire to see the pathways improved and not reined in. Companies take issue with regulators, regulators take issue with companies, each take issue with their peers, and payers have their own set of complaints. 

Still, this is unfolding against a backdrop of progress that is almost certain to dramatically change the conversation.

Technologies are emerging, science unfolding and ideas evolving that could see these pathways not only become routine in many diseases, but spawn innovation, reshape regulatory toolboxes and serve as testing grounds for innovative pricing models.

Over the next five days, Back to School will publish a collection of articles organized around the three stages of the process: creating an approvable data package, collecting postmarket data to confirm benefit, and using the data to grant full approval or withdraw or modify the initial approval. BioCentury’s editors will discuss the topic of the day on a special BioCentury This Week podcast. The package culminates with an overarching essay that projects the stretch vision for accelerated approval.

Today’s articles cover the big picture, setting the stage with a data-rich analysis by Executive Editor Selina Koch of the promise and problems of accelerated approval and an in-depth case study of the pathway’s use in cancer. These are accompanied by a data graphic on the poster child of accelerated approval, Keytruda pembrolizumab from Merck & Co. Inc. (NYSE:MRK), by Director of Data & Analytics Winnie Pong.

On Tuesday, Back to School focuses on the first stage, creating an approvable data package, where the big issue centers on the standards of evidence required for an accelerated or conditional approval. Senior Editor Lauren Martz picks apart the issues surrounding surrogate endpoints, homing in on the standard, defined by law, that requires these to be “reasonably likely” to predict clinical benefit, and the complexities that creates.

Senior Editor Karen Tkach Tuzman picks up the thread with an article on emerging surrogate endpoints nearing approval. In a separate article, she takes the long view, examining how next-generation omics tools are converging to support the stretch vision by creating insights into disease biology that could fuel a radically expanded biomarker toolbox, and a growing roster of surrogate endpoints across many diseases. 

On Wednesday, Back to School takes a fresh angle on the second stage, confirmation via postmarket trials, with an article from Martz that argues for viewing the studies as a platform for innovation rather than a box to check to satisfy regulators. Using the trials to create a fuller view of which patients are likely to receive how much benefit would be of huge value to patients, physicians and payers. 

Part of that will involve the use of real-world evidence, which Martz digs into in a sister article. 

Associate Editor Stephen Hansen explores the ins and outs of EMA’s approach, which involves tandem pathways — conditional approval, a process that carries the requirement for postmarket trials, and exceptional circumstances, a pathway designed for cases where it is either unethical or unreasonable to expect comprehensive data can be obtained.

This is accompanied by an analysis by Hansen of the reasons behind Europe’s growing appetite for conditional approval, and a dive into the data comparing approvals by EMA and FDA, looking at areas of overlap and difference, by Meredith Durkin Wolfe, associate editor of data & analytics. 

Back to School analyzes the issues surrounding last stage of the pathway, the decision either to grant full approval or withdraw a drug, on Thursday.

In a pair of articles, Washington Editor Steve Usdin provides a comprehensive analysis of the forces surrounding market access, finding both regulators and payers are limited by the binary options available to them. The stretch vision would see regulators endowed with regulatory “rheostats” that allow them to tailor access to the drugs to the right patients, and payers deploy value-based payment models to couple reimbursement to the level of certainty of the evidence.

Hansen adds analysis of the relatively new pathways in China and Japan in one article, and the very new process in the U.K. in another, all of which take steps along the path to the stretch vision.

On Friday, BioCentury will publish the annual Back to School essay, which builds on the articles of the week and draws an overarching picture of the stretch vision — a learning system across pre- and postmarket studies that brings more drugs to more patients in more diseases. 

As the issue of accelerated approvals continues to occupy the spotlight, and forces gather to fix the flaws, we hope this package both provides a compendium of information and provokes thought and conversation about how best to maximize the potential of the pathways globally and stretch the vision of what they can to deliver for patients.