As biopharma companies move into 2023 with a focus on product development, establishing priorities, and committing to future milestones, it also is critical to pay attention to emerging U.S. Federal Food and Drug Administration (FDA) trends.
FDA’s Center for Drug Evaluation and Research (CDER) recently released its annual report, “Advancing Health Through Innovation: New Drug Therapy Approvals 2022,” which summarized the 37 novel drugs and biologics approved by CDER in 2022.
37 is a notable drop from the previous 5-year average of 51 novel drugs and biologic approvals per year [2021 (50), 2020 (53), 2019 (48), 2018 (59), 2017 (46)].
While the reasons behind this decline are unclear, CDER seems to provide some insight with the following statements on page five of the report, “The number of drug applications CDER received in 2022 was similar to the past few years (and higher than historical norms), demonstrating that innovation remains strong in the drug development sector. CDER only approves drug and biologic applications that meet our high regulatory standards.”
While CDER confirms that new drug application (NDA) and biologic license application (BLA) submission numbers are consistent with recent years, they confirm they only approve applications that meet their high standards, which suggests the Agency found more 2022 applications to be inadequate in their content.
What’s Behind the 2022 CDER Decline in Marketing Application Approvals for Novel Drugs?
CDER approved 76% (28/37) of the 37 novel drugs and biologics on the first cycle of review. A first approval means these applications were approved on the first cycle of review and did not receive a Complete Response Letter (CRL) – a letter from the FDA determining they will not approve the application in its present form for one or more reasons given. The metric of first cycle approval can be interpreted as a pulse on the overall quality and acceptability of applications. But the 2022 first cycle approval rate of 76% (28/37) is a substantial decrease compared to the previous 5‑year average of 90% [2021 (86%), 2020 (92%), 2019 (90%), 2018 (95%), 2017 (85%)].
In 2022, FDA continued to support product development for drugs and biologics for rare diseases and patients with unmet medical needs, as 65% (24/37) of novel drug and biologic approvals used at least one or more expedited programs — Fast Track, Breakthrough Therapy, Priority Review, and/or Accelerated Approval – consistent with the approvals over the previous 5 years.
Interestingly, while the Accelerated Approval program accounted for an increase in the total approvals over the last few years (28% in 2021 [14/50]; 23% in 2020 [12/53]), that number dipped back down to 16% (6/37) in 2022. It appears that the pendulum regarding approvals granted based on surrogate/predictive endpoints and future post-marketing commitments may be swinging back. This is unsurprising given the ongoing conversation driven by FDA Commissioner, Robert Califf, M.D., and Director of the Oncology Center for Excellence (OCE), Richard Pazdur, M.D. Additionally, there is controversy surrounding the congressional investigation into the 2021 approval of Biogen’s Aduhelm drug for Alzheimer’s disease. The Agency may be increasing scrutiny around which applications are granted approval based on these criteria.
These sentiments were recently reiterated during Commissioner Califf’s comments while speaking on a panel at the 2023 JP Morgan Conference. Regarding confirmatory trials, Califf stated in a panel discussion, “I felt for a long time that we haven’t held on to the second part of the bargain, which is if you’ve got accelerated approval … you should be committed to getting the answer as to whether it actually really works.”
And on the topic of the Aduhelm investigation, he noted, “Have you ever seen a congressional investigation that said, ‘These folks are doing a great job?’ There were some things that the FDA can do better, and we fully acknowledge that.”
Navigating the Approval Headwinds
The FDA consistently encourages drug developers to take advantage of the use of expedited programs, like Breakthrough Therapy designation and Accelerated Approval, that allow early and frequent engagement with the FDA to ensure high-quality and approvable applications per their standards. For example, the FDA is signaling a more collaborative environment with the introduction of INTERACT meetings (an early interaction intended to facilitate IND-enabling efforts where the sponsor is facing a novel, challenging issue that might delay progress into the clinic without FDA input) and Type D meetings (a meeting focused on a narrow set of issues) for drugs in CDER as part of the Prescription Drug User Fee Act (PDUFA VII).
Still, at the heart of an acceptable application is strong safety and efficacy data to support the application. Whether these applications are for Accelerated Approvals or not, the outcome is mostly determined by the strength of the supporting data that is well presented and easily understood by FDA reviewers. In order to bolster the opportunity of application approval, the sponsor should be certain while preparing their submission that their team performs the right due diligence to ensure the data is presented in the correct FDA-acceptable data formats and is presented in a clear and coherent manner. Recognizing the workload at the FDA is immense, despite Divisions aggressively recruiting new hires under PDUFA VII commitments, failure to incorporate the right due diligence on data in the face of pressures to move fast in the development and review process runs the risk of a delayed approval.
There certainly are headwinds facing approvals as we enter 2023. Though the acceptability of marketing applications was down in 2022, going forward, it will be imperative to ensure the quality of your data, identify gaps in your application well before submission, and prepare for FDA communications and assessments to propel your product development.
To learn more about Halloran’s regulatory services – health authority meetings and interactions, special designations, and marketing application insight – please contact a member of our team.
Halloran is also releasing content on the Food and Drug Omnibus Reform Act (FDORA) and how this impacts Accelerated Approvals. Please stay tuned for our insights.