6 ways the new FDA can turbocharge drug development
Proposal 1. Establish a U.S. equivalent of Australia’s Clinical Trial Notification (CTN) scheme
Adopting a Clinical Trial Notification (CTN) model—where ethics committees approve protocols and the FDA is simply notified—could dramatically cut startup times while maintaining safety oversight.
Rationale:
The FDA's current IND approval process significantly slows the initiation of early-stage trials, leading to higher costs and delays in bringing new therapies to patients.
Supporting Evidence:
Australia's CTN model expedites Phase 1 trial starts within 6–12 weeks, compared to months-long FDA IND reviews.
Lower regulatory burden reduces Phase 1 trial costs to $1–2M in Australia vs. $3–4M+ in the U.S., aided by a 43.5% R&D tax rebate.
Proposal 2. Expand Project Orbis and appeal 21 CFR 312.120 to get more Phase III trials accepted by FDA
Greater use of international trial standards (ICH E5/E17) and collaboration could reduce redundancy – e.g. FDA’s acceptance of EU or Japan Phase III results.
Rationale:
The FDA can approve drugs based on overseas trials (per 21 CFR 312.120), but requires that trials meet FDA’s quality standards and represent U.S. populations; Project Orbis, launched by the FDA in 2019, provides a framework for concurrent review of oncology drugs by the U.S., EU, UK, Japan, Canada, Australia and others.
Supporting Evidence:
21 CFR 312.120:
A notable case of 21 CFR 312.120 overstepping a drug approval was an immunotherapy (sintilimab) tested entirely in China: despite a positive trial, FDA advisors refused approval due to concerns that the single-country study (with an outdated chemo comparator and homogeneous population) might not generalize to U.S. patients.
Project Orbis:
Project Orbis has significantly accelerated cancer drug availability: in 2020 alone, Orbis led to 17 new oncology drugs and 32 new indications being approved simultaneously in multiple countries
By 2023, FDA had listed 68 Orbis drug approvals with most partner agencies approving those drugs around the same time.
Proposal 3. Establish a "Genetic Priority Designation" for drug approval
A formal "Genetic Priority Designation" should be established for therapies with well-supported genetic underpinnings, expediting their review process.
Rationale:
Genetic evidence from GWAS and Mendelian randomization studies provides strong causal links between biological pathways and disease. The FDA should integrate these data more explicitly into accelerated approval pathways, allowing earlier surrogate endpoint approvals for drugs (especially monoclonal antibodies and siRNA/ASOs) targeting genetically validated mechanisms.
Supporting Evidence:
PCSK9 inhibitors were approved based on Mendelian randomization data linking LDL to cardiovascular risk
Lipoprotein(a) inhibitors received FDA Fast Track designation based on strong genetic data
FDA used breakthrough therapy for Evkeeza, given the genetic evidence of ANGPTL3 LoF
Case studies in progress include drugs targeting APOE ε4 for Alzheimer’s (genetics identifies a high-risk subgroup) and INHBE for obesity (loss-of-function MR suggests targeting it might be beneficial).
Proposal 4. Establish a public database of failed and discontinued clinical trials
Sharing non-sensitive failed trial data (preclinical findings, trial outcomes, etc., without revealing proprietary chemistry) could prevent duplicative efforts and guide new research.
Rationale:
Currently, if a company’s IND or NDA fails, most data remains secret, which means other researchers might repeat similar trials in ignorance. For example, if a certain mechanism doesn’t work despite a robust Phase 3 trial, publishing that result (even if negative) allows the scientific community to redirect efforts – saving time and R&D dollars (1, 2)
Supporting Evidence:
Analyses suggest that concerns that transparency would harm innovation are unfounded–on the contrary, cumulative knowledge from both successes and failures drives efficiency in drug discovery.
Proposal 5. Develop an “Aging Drug Designation”
Grant extended market exclusivity for drugs approved to treat diseases of aging.
Rationale:
Aging-related diseases present a unique challenge – conditions like Alzheimer’s, osteoarthritis, frailty, and others that affect millions and have huge societal impact. They aren’t “rare,” so the Orphan Act’s market exclusivity incentives don’t apply, and companies can be reluctant to pursue them due to high failure rates.
Supporting Evidence:
Since its passing in 1983, the Orphan Drug Act has lead to more than 882 drug approvals for rare diseases with high unmet need. The total number of medication approved prior to the Orphan Drug Act was a paltry list of 38 drugs.
Proposal 6. Penalize patent life of “me too” drugs
Shorten monopoly time for drugs that aren’t novel in mechanism of action; or lack improved dosing regimen, or enhanced safety/tolerability.
Rationale:
The patent and exclusivity system is meant to reward innovation, but it often extends monopolies for drugs that show minimal improvements (“me-too” or “evergreened” drugs). Pharmaceutical companies frequently make slight modifications to existing drugs – e.g. a new isomer, a prodrug, an extended-release formulation, or a new combination – and obtain new patents or FDA exclusivities, blocking generics and prolonging high prices despite little added clinical value.
Supporting Evidence:
A classic example of an evergreened drug is esomeprazole (Nexium), the single-isomer form of omeprazole (Prilosec).
Nexium was patented and marketed as an improved therapy, but its efficacy was nearly identical to omeprazole; nonetheless, the new patent/exclusivity period let the manufacturer retain market control.
Numerous “line extensions” follow this pattern (e.g. escitalopram vs citalopram, controlled-release ADHD stimulants, insulin analog tweaks).
Studies by health technology assessors in Europe have found that over half of new drug approvals offer no or only minor additional benefit for patients.