The internal government fight over new drugs
Recently you may have heard that the U.S. Food and Drug Administration (FDA) has released a collection of more than 200 CRLs (Complete Response Letters) as part of it’s self-proclaimed “commitment to transparency”. The initiative aims to enhance public understanding of the rationale behind the rejection of certain new drug and biologic applications. Given the scrutiny government agencies have received in recent months, one can only assume this is a signal flare to the public, that policy-makers can only fabricate so much of the narrative.
With the recent announcement, the publication of these CRLs reflects the agency’s effort to foster “radical transparency.” The letters, now available through openFDA, include responses issued to both large pharmaceutical companies such as Eli Lilly and Regeneron, as well as smaller biotechnology firms, covering a range of therapeutic indications.
FDA Commissioner Marty Makary stated, “For far too long, drug developers have been playing a guessing game when navigating the FDA. Drug developers and capital markets alike want predictability. So today we’re one step closer to delivering it to them, with an ultimate goal of bringing cures and meaningful treatments to patients faster.”
A 2015 agency analysis revealed that 85% of companies did not disclose safety and efficacy concerns from the FDA when announcing application rejections. The FDA noted that insufficient sharing of insights from non-approvals has resulted in recurring errors within the industry. The marathon between drug target creation and product market is colloquially referred to as the “valley of death” – shrewdly named due to the low percentage of approvals within these phases of the process. The recent floor of approval ratings only raises more eyebrows of the public concerning trial efficacy.
But what does this mean and why do I care?
This release represents the initial group of CRLs, all pertaining to applications that have subsequently received approval after some form of Request for Information or rejection altogether. Examples include a June 2023 letter for Regeneron’s Eylea HD (for retinal disease), a 2017 rejection of Daiichi Sankyo’s chewable gum formulation of Welchol (cholesterol treatment), and a February 2010 response regarding Cadence Pharmaceuticals’ Ofirmev (an injectable acetaminophen), citing manufacturing deficiencies at a Mississippi facility.
In recent months, the FDA has experienced organizational changes in response to government administration review and planned reduction in staff. By early April, more than half of it’s senior leadership had left their positions. The administration has received feedback regarding layoffs, delays in advisory committee meetings, and the rescheduling of events such as Rare Disease Day.
The release of Complete Response Letters is a positive and commendable step towards greater transparency and accountability. By providing valuable insights into the reasons behind drug application rejections, the FDA is fostering a more predictable regulatory environment and encouraging better practices within the pharmaceutical industry. This initiative ultimately benefits patients [and hopeful drugmakers] by ensuring that new treatments are safe, effective, and brought to market as quickly as possible.