FDA reject over 20 new drugs ,Multinational approved drugs also face setbacks,what are the main reasons are?
First Hurdle: Critical Flaws in Efficacy Data
Critical flaws in efficacy data render clinical significance paramount. Numerous drugs have been rejected due to "insufficient evidence." Sanofi's $3.7 billion acquisition of the BTK inhibitor Telebrutinib was declined for its multiple sclerosis indication due to high liver injury risks and ambiguous benefit populations. GlaxoSmithKline's Blenrep not only failed to meet key efficacy endpoints but also had an enrollment rate of less than 5% among U.S. patients, prompting direct FDA questioning of data applicability. Even if a trial demonstrates statistical differences, it still fails to pass scrutiny if its clinical value is questionable.
Stage Two: Production Compliance Red Lines
Production issues are emerging as the "primary obstacle" to new drug approvals. Multiple rejection letters issued in 2025 pointed to CMC (Chemistry, Manufacturing, and Controls) deficiencies: Hengrui Medicine's "Dual-Ai" therapy (carrelizumab + apatinib) faced two rejections due to production process defects; Scholar Rock's novel drug for spinal muscular atrophy and Regeneron's bispecific antibody for lymphoma were both delayed in approval due to compliance issues with third-party manufacturer Catalent. More critically, FDA analysis revealed that 56% of rejection letters involved production facility inspection issues, ranging from data integrity to cleanroom validation, where any detail oversight could trigger a red flag.
Third Hurdle: Safety Risks
The FDA's safety review is notoriously nitpicky. Luye Pharma's risperidone extended-release injection was flagged for a "dose surge" risk after three patients exhibited a 5-fold increase in blood drug concentration from baseline. PTC's Friedreich's ataxia drug Vatiquinone was required to conduct new controlled trials due to insufficient safety data from existing studies. Even drugs approved in other countries can be halted if safety data for the U.S. population is inadequate.
However, FDA rejections are not "death sentences." Pfizer's Ngenla was approved the following year after supplementary data submission; Johnson & Johnson's evolocumab and Astellas 'zotumumab both received rejection letters but were cleared after rectification. In 2025, the FDA announced real-time public disclosure of rejection letters, providing drugmakers with "rectification guidelines" while compelling the industry to raise standards.
For companies aiming to enter the U.S. market, this rejection storm serves as a wake-up call: to secure FDA approval, innovation alone is not enough—meticulous attention to clinical design, manufacturing compliance, and safety validation is essential. After all, in the FDA's review logic, "patient benefit" remains an unbreachable baseline.