US Pharmaceuticals Inc. – FDA CRL

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for Telix Pharmaceuticals (US) Inc.'s New Drug Application (NDA 218592) for floretyrosine F 18 injection. The agency determined that the application, in its present form, cannot be approved due to significant clinical and statistical deficiencies.

The main issue identified was the lack of substantial evidence of effectiveness for floretyrosine F 18. The pivotal efficacy study, 18F-TLX101-CDx-203, demonstrated only borderline diagnostic performance, with lower bounds for sensitivity ranging from 58% to 73% and specificity from 36% to 51%. The study was also noted as a single-center trial with potential for bias in reference standard determination. Confirmatory evidence provided was deemed insufficiently strong due to various design flaws, including inconsistent evaluation methods and potential for unblinding.

To address these deficiencies, the FDA requires Telix Pharmaceuticals to conduct a second adequate and well-controlled efficacy study or provide other robust confirmatory evidence of efficacy. Optimization of the administered dose could also be considered. Additionally, a comprehensive safety update, as described in 21 CFR 314.50(d)(5)(vi)(b), must be submitted, detailing all new safety data, significant changes in the safety profile, and worldwide experience. Telix Pharmaceuticals has one year to resubmit a complete response to these issues; otherwise, the application may be considered withdrawn.