Amgen, Inc. – FDA CRL

The FDA issued a Complete Response Letter (CRL) to Amgen, Inc. for its Biologics License Application (BLA 125522/Original 2) concerning Repatha (evolocumab), 420 mg administered every two weeks, for homozygous familial hypercholesterolemia (HoFH). No specific inspection dates were detailed in this BLA review document. Submitted under section 351(a) of the Public Health Service Act, the application was not approved primarily due to insufficient clinical data. The main issue identified was the lack of adequate and well-controlled studies to clearly describe the incremental benefit, if any, of the 420 mg every two-week dosing regimen when compared to the 420 mg once-monthly regimen for HoFH patients on other lipid-lowering therapies. The FDA determined the existing data were inadequate to characterize this specific dosing frequency. Required actions for Amgen include conducting and submitting additional clinical information from new studies to better define this dosing regimen. Furthermore, a comprehensive safety update is mandated, encompassing new non-clinical and clinical data, a detailed description of any significant changes in the safety profile, combined and comparative adverse event frequencies, updated exposure information, a summary of worldwide safety experience, and English translations of foreign labeling. Labeling comments are deferred until these clinical and safety deficiencies are resolved. Amgen must resubmit within one year, addressing all identified deficiencies as per 21 CFR 601.3(b), otherwise, the application may be considered withdrawn. Marketing of this specific Repatha regimen is prohibited until approval.