CBER Biological Product Approvals that Used Real-World Evidence
FDA Use of Real-World Evidence in Regulatory Decision Making
510(k) - 510(k) premarket notification
ACE - Angiotensin-converting enzyme
AEMS – Adverse Event Monitoring System
ARB - Angiotensin receptor blocker
BLA - Biologics License Application
CBER - Center for Biologics Evaluation and Research
CDER - Center for Drug Evaluation and Research
CDRH - Center for Devices and Radiological Health
CMS - Center for Medicare and Medicaid Services
DSC - Drug Safety Communication
EHR- Electronic health records
EMR - Electronic medical records
ESA - Erythropoietin stimulating agent
GBCA - Gadolinium-based contrast agent
GLP-1 RA - Glucagon-like peptide-1 receptor agonists
HCTZ - Hydrochlorothiazide
HDE - Humanitarian device exemption
IAA - Inter-Agency Agreement
IDE - Investigational Device Exemption
MACE - Major adverse cardiac event
NDA - New Drug Application
OSE - Office of Surveillance and Epidemiology
OUS - Outside the U.S.
PLLR - Pregnancy and Lactation Labeling Rule
PMA - Premarket approval application
PPI - Proton pump inhibitor
REMS - Risk Evaluation and Mitigation Strategy
RWD - Real-World Data
RWE - Real-World Evidence
SEE – Substantial Evidence of Effectiveness
U.S. - United States
VHA - Veterans Health Administration
VTE - Venous thromboembolism
| Product Name & Number | Sponsor/Applicant | Data Source(s) | Data Source Description(s) | Study Design(s) | Summary of RWE use and/or Regulatory Action | Type / Date of Regulatory Action(s) and/or Other Action(s) | Related Document(s) or Communication(s) |
|---|---|---|---|---|---|---|---|
| ZOLGENSMA (onasemnogene abeparvovec-xioi) BLA 125694/0 | AveXis, Inc | Medical records | Natural history data of infants with spinal muscular atrophy (SMA) | Externally Controlled Trial | RWE contributed to substantial evidence of effectiveness (SEE): Natural history data served as the external control in single-arm study to support approval for treatment of pediatric patients under 2 years of age with SMA. Comparison to the natural history control demonstrated improvement in survival and achievement of developmental motor milestones. | Approval: 5/24/2019 | ZOLGENSMA |
| RETHYMIC (allogeneic processed thymus tissue-agdc) BLA 125685/0 | Enzyvant Therapeutics GmbH | Medical records | Natural history study of 49 patients with congenital athymia | Externally Controlled Trial | RWE contributed to SEE: Natural history data served as the external control compared to pooled clinical data from 10 open-label studies to support approval for immune reconstitution in pediatric patients with congenital athymia, based on the endpoint of mortality and large treatment effect size. | Approval: 10/8/2021 | RETHYMIC |
| LANTIDRA (donislecel-jujn) BLA 125734/0 | CellTrans Inc. | Medical records | Well-established natural history of Type 1 diabetes | Externally Controlled Trial | RWE contributed to SEE: Data from two single-arm studies (UIH-001 and UIH-002) were compared to the well-established natural history of Type 1 diabetes to comprise a single adequate and well-controlled investigation supporting approval for treatment of adults with Type 1 diabetes who experience repeated episodes of severe hypoglycemia. | Approval: 6/28/2023 | LANTIDRA |
| KEBILIDI (eladocagene exuparvovec-tneq) BLA 125722/0 | PTC Therapeutics, Inc. | Medical records | External cohort of 44 untreated patients with severe AADC deficiency | Externally Controlled Trial | RWE contributed to SEE: A single-arm pivotal study (n=12) and an external control natural history cohort of 44 untreated patients with severe AADC deficiency comprised a single adequate and well-controlled investigation to support accelerated approval for treatment of adult and pediatric patients with AADC deficiency. Continued approval is contingent upon verification of long-term clinical benefit in a confirmatory study. | Accelerated Approval: 11/13/2024 | KEBILIDI |
| COAGADEX (Coagulation Factor X (Human)) BLA 125506/46 | BioProducts Laboratory, Limited | Medical records | Compassionate use data from clinical practice prior to licensure | Descriptive | Retrospective survey of compassionate use of COAGADEX in 15 patients of all ages prior to licensure submitted alongside a prospective trial in 9 children under 12 years of age to support an efficacy supplement for routine prophylaxis to reduce the frequency of bleeding episodes and removal of the age restriction for on-demand treatment and perioperative management of bleeding in patients with hereditary Factor X deficiency. | Approval, Efficacy Supplement: 9/21/2018 | COAGADEX |
| VONVENDI (recombinant von Willebrand Factor, rVWF) BLA 125577/118 | Takeda Pharmaceuticals USA, Inc. | Multiple | ATHN database registry: patient medical records, assessments, laboratory testing, and patient diaries | Multiple | Supportive evidence: RWE from two studies (ATHN 9: Natural History and CCR-2024-200475: Retrospective analysis of the safety and effectiveness of surgery management with Vonvendi of pediatric VWD patients) were submitted alongside clinical trials for indication expansion. | Approval, Indication Exapansion: 9/5/2025 | VONVENDI |
| ZOSTAVAX (Zoster vaccine live) BLA 125123/2058 | Merck Sharp & Dohme Corp | Multiple | Kaiser Permanente Northern California (KPNC) integrated healthcare system database | Cohort | Prospective observational cohort study used to update the prescribing information with long-term effectiveness data against herpes zoster and postherpetic neuralgia in individuals 50 years of age and older. | Labeling Update: 4/19/2018 | ZOSTAVAX |
| Lenmeldy (Atidarsagene Autotemcel) BLA 125758 | Orchard Therapeutics (Europe) Limited | Medical records | Medical Records (European Union) | Externally Controlled Trial | RWE from an externally controlled trial with an untreated arm from a natural history study (plus untreated siblings not in the natural history study) was a primary source of clinical evidence of effectiveness to support approval for treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD). | Approval: 03/18/2024 | Lenmeldy |
| Skysona (Elivaldogene Autotemcel) BLA 125755 | Bluebird Bio, Inc. | Medical records | Medical Records from a natural history study (Global) | Externally Controlled Trial | RWE from an externally controlled trial with an untreated arm from a natural history study and allo-HSCT treated arm from a non-interventional study, was a primary source of clinical evidence of effectiveness from a single adequate and well-controlled investigation to support accelerated approval for indication of slowing the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD). | Approval: 09/16/2022 | Skysona |