brincidofovir IV (BCV IV) / SymBio Pharma, Jazz - LARVOL DELTA

Adenovirus infection after cellular therapy: diagnostic and therapeutic challenges. (PubMed, Curr Opin Infect Dis) - "HAdV remains an important cause of morbidity and mortality following HCT, particularly in patients with impaired T-cell immunity. Key challenges include optimal surveillance strategies, treatment thresholds, and management of high-risk patients. Advances in molecular diagnostics, standardized disease definitions, brincidofovir, and virus-specific T-cell therapies may facilitate higher quality clinical research and support more standardized, evidence-based approaches to HAdV management."

Journal • Gastrointestinal Disorder • Infectious Disease • Transplantation

A study comparing Brincidofovir administered as an oral suspension versus Intravenous Formulation in Japanese and Non-Japanese Adult Volunteers (ANZCTR) - P1 | N=36 | Completed | Sponsor: Chimerix Inc. | Not yet recruiting ➔ Completed

Trial completion • Epstein-Barr Virus Infections • Infectious Disease • Oncology

Dose-dependent efficacy of intravenous brincidofovir across adenovirus species in immunocompromised patients. (PubMed, J Infect) - "These findings support a dose-dependent broad efficacy of intravenous BCV across all relevant HAdV species and set the stage for an ensuing phase 3 trial, facilitating future regulatory approval of the compound for this urgently needed indication."

Journal • Infectious Disease

ATHENA: A Phase 2a Study of IV BCV in Subjects With Adenovirus Infection (clinicaltrials.gov) - P2 | N=53 | Completed | Sponsor: SymBio Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Cytomegalovirus Infection • Infectious Disease

Adenovirus Infections in Hematologic Malignancy and Hematopoietic Cell Transplant Recipients: Epidemiology, Diagnosis, and Management. (PubMed, Infect Chemother) - "Intravenous cidofovir remains the most widely used antiviral despite nephrotoxicity, while intravenous brincidofovir represents a potentially promising emerging approach. The impact of contemporary transplant approaches, including post-transplant cyclophosphamide and novel cellular therapies, on HAdV epidemiology requires further study. This review summarizes contemporary epidemiology, definitions, diagnostic strategies, and evolving therapeutic options for HAdV infection in patients with hematologic malignancies, highlighting ongoing challenges."

Journal • Review • Bone Marrow Transplantation • Cardiovascular • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Pediatrics • Pneumonia • Transplantation

Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Rare Diseases

Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

New P2 trial • CNS Disorders • Rare Diseases

Delayed intestinal adenovirus response to intravenous brincidofovir in paediatric allogeneic stem cell transplant recipients displaying rapid clearance of the virus from peripheral blood. (PubMed, Clin Microbiol Infect) - No abstract available

Journal • Pediatrics • Transplantation

Disseminated vegetative Mpox in an immunocompromised patient (AAD 2026) - "Tecovirimat, brincidofovir, and intravenous vaccina immune globulin were administered under expanded access protocol for immunosuppressed patients and the ulcers quickly epithelialized. Recognition of Mpox in patients with advanced HIV is critical, as severe, protracted disease can occur with significant morbidity and heightened transmission risk. This case highlights the evolving spectrum of Mpox presentations in immunocompromised populations, reinforces the importance of HIV screening in patients with atypical or severe eruptions, and underscores the dermatologist's role in early identification, management, and infection control during ongoing outbreaks."

Clinical • Herpes Simplex • Herpes Zoster • Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases • Tuberculosis • Varicella Zoster • CD4

INTRAVENOUS BRINCIDOFOVIR EFFECTIVELY REDUCES CMV DNAEMIA IN ANTIVIRAL EXPERIENCED IMMUNOCOMPROMISED PATIENTS: RESULTS OF A PHASE 2A CLINICAL TRIAL (EBMT 2026) - P2 | "Brincidofovir (BCV) is a lipid conjugate of cidofovir that overcomes cidofovir's dose-limiting nephrotoxicity while enhancing antiviral activity against CMV and other double-stranded DNA viruses...Most patients (7/9 per Cohort) had failed ≥1 prior CMV antiviral (n=12 GCV or valGCV, 4 foscarnet, 4 letermovir, and 2 maribavir)... IV BCV was effective in reducing CMV DNAemia and was reasonably well tolerated in this population of pre-treated immunocompromised patients with CMV viremia. IV BCV is a potential treatment option for these patients with limited treatment options. These data support further study of IV BCV for treatment of CMV infections in immunocompromised patients."

Clinical • P2a data • Bone Marrow Transplantation • Cytomegalovirus Infection • Infectious Disease

ENOVIA: A Phase 3 Trial to Compare IV BCV Versus IV CDV for Treatment of Adenovirus Infection After Allo-HCT (clinicaltrials.gov) - P3 | N=180 | Recruiting | Sponsor: SymBio Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Pediatrics • Transplantation

BCV-PA02: Efficacy and safety study of intravenous brincidofovir compared to intravenous cidofovir for the treatment of adenovirus infection in children and adults after stem cell transplant (clinicaltrialsregister.eu) - P2/3 | N=72 | Not yet recruiting | Sponsor: Symbio Pharmaceuticals Ltd.

New P2/3 trial • Infectious Disease • Pediatrics • Transplantation

Intravenous Brincidofovir Effectively Reduces CMV Dnaemia In Antiviral Experienced Immunocompromised Patients: Results of a Phase 2a Clinical Trial (TCT-ASTCT-CIBMTR 2026) - P2 | "Most patients (7/9 per Cohort) had failed ≥1 prior CMV antiviral (n=12 GCV or valGCV, 4 foscarnet, 4 letermovir, and 2 maribavir). IV BCV was effective in reducing CMV DNAemia and was reasonably well tolerated in this population of pre-treated immunocompromised patients. IV BCV is a potential treatment for patients with limited options. These data support further study of IV BCV for treatment of CMV infections."

Clinical • Late-breaking abstract • P2a data • Bone Marrow Transplantation • Cytomegalovirus Infection • Infectious Disease

ENOVIA: A Phase 3 Trial to Compare IV BCV Versus IV CDV for Treatment of Adenovirus Infection After Allo-HCT (clinicaltrials.gov) - P3 | N=180 | Not yet recruiting | Sponsor: SymBio Pharmaceuticals

New P3 trial • Infectious Disease • Pediatrics • Transplantation

A Phase 1b/2 Study of Intravenous Brincidofovir in Patients With Relapsed or Refractory Lymphoma and Relapsed or Refractory Extranodal Natural Killer/T-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=43 | Suspended | Sponsor: SymBio Pharmaceuticals | Recruiting ➔ Suspended

Trial suspension • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Preliminary Results of a Phase 2a Clinical Trial to Evaluate Safety, Tolerability and Antiviral Activity of Intravenous Brincidofovir (BCV IV) in Immunocompromised Patients with Adenovirus Infection (ASH 2023) - P2 | "Brincidofovir (BCV) is a lipid conjugate of cidofovir, that crosses target cell membranes by means of facilitated and passive diffusion and has a long intracellular half-life. BCV IV was found to be safe and well tolerated in immunocompromised patients. Notably, the potentially serious gastrointestinal and hepatic toxicities described with the oral BCV formulation were not observed. BCV IV was highly effective in a dose-dependent manner, led to rapid clearance of AdV viremia within a short treatment period and provided sustained virologic response."

Clinical • P2a data • Infectious Disease

Investigational treatments for cytomegalovirus infection in phase I and II study. (PubMed, Expert Opin Investig Drugs) - "Despite recent advances in CMV chemoprevention and treatment in transplant recipients, there remains a need for a broader, more diversified approach to mitigating the impact of CMV infection in both transplant and non-immunocompromised persons. Intravenous brincidofovir would provide an important alternative option to current antivirals in the right clinical setting. Several promising vaccine candidates are in various stages of clinical development. A safe and effective vaccine may also expand preventative strategies beyond transplant recipients and into healthy persons, specifically for the prevention of maternal-to-fetal transmission. The therapeutic possibilities of VST and TCR therapy represent important potential adjuncts to antivirals."

Journal • P1 data • Review • Cytomegalovirus Infection • Infectious Disease • Transplantation

A Phase 1b/2 Study of Intravenous Brincidofovir in Patients With Relapsed or Refractory Lymphoma and Relapsed or Refractory Extranodal Natural Killer/T-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=43 | Recruiting | Sponsor: SymBio Pharmaceuticals

New P1/2 trial • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Adenoviremia Clearance Following Treatment with Intravenous (IV) Brincidofovir (BCV) in Immunocompromised Patients is Associated with Positive Clinical Disease Response: Preliminary Outcomes from the ATHENA Phase IIa Study (IDWeek 2024) - No abstract available

Clinical • P2a data • Infectious Disease

ATHENA: A Phase 2a Study of IV BCV in Subjects With Adenovirus Infection (clinicaltrials.gov) - P2 | N=52 | Recruiting | Sponsor: SymBio Pharmaceuticals | N=24 ➔ 52

Enrollment change • Cytomegalovirus Infection • Infectious Disease

A Phase 2a Study of IV BCV in Subjects With Adenovirus Infection (ATHENA) (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: SymBio Pharmaceuticals | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2023 ➔ Sep 2026 | Trial primary completion date: Dec 2023 ➔ Sep 2026

Phase classification • Trial completion date • Trial primary completion date • Infectious Disease

Intravenous brincidofovir rapidly clears adenoviremia in immunocompromised patients: interim results from Phase 2a ATHENA study (ECCMID 2024) - No abstract available

Clinical • Late-breaking abstract • P2a data

PRELIMINARY RESULTS OF PHASE 2A CLINICAL TRIAL TO EVALUATE SAFETY, TOLERABILITY AND ANTIVIRAL ACTIVITY OF INTRAVENOUS BRINCIDOFOVIR IN IMMUNOCOMPROMISED PATIENTS WITH ADENOVIRUS INFECTION (EBMT 2024) - P2a | "Brincidofovir (BCV) is a lipid conjugate of cidofovir, that crosses cell membranes and has a long intracellular half-life. IV BCV was found to be safe and well tolerated in immunocompromised patients. Notably, the potentially serious gastrointestinal and hepatic toxicities described with the oral BCV formulation were not observed. IV BCV was highly effective in a dose-dependent manner, led to rapid clearance of AdV from blood and stool within a short treatment period and provided sustained virologic response."

Clinical • P2a data • Gastrointestinal Disorder • Hepatology • Infectious Disease • Pediatrics • Solid Organ Transplantation • Transplantation

Preliminary Results of a Phase 2a Clinical Trial to Evaluate Safety, Tolerability and Antiviral Activity of Intravenous Brincidofovir (BCV IV) in Immunocompromised Patients with Adenovirus Infection (TCT-ASTCT-CIBMTR 2024) - P2a | "Brincidofovir (BCV) is a lipid conjugate of cidofovir, that crosses cell membranes and has a long intracellular half-life. BCV IV was found to be safe and well tolerated in immunocompromised patients. Notably, the potentially serious gastrointestinal and hepatic toxicities described with the oral BCV formulation were not observed. BCV IV was highly effective in a dose-dependent manner, led to rapid clearance of AdV from blood and stool within a short treatment period and provided sustained virologic response."

Clinical • P2a data • Gastrointestinal Disorder • Hepatology • Infectious Disease • Pediatrics • Transplantation

Utility of Cytochrome P450 4F2 Genotyping to Assess Drug Interaction Risk for Brincidovovir, a Cytochrome P450 4F2 Substrate. (PubMed, Clin Pharmacol Drug Dev) - "Genotyping was performed on blood from healthy participants receiving oral (n = 261) and intravenous (IV, n = 49) brincidofovir across 6 phase 1 trials...Little to no increase in brincidofovir exposure parameters was observed following IV administration. Based on the lack of significant increases in brincidofovir plasma concentrations in subjects with low activity CYP4F2, a clinically meaningful drug-drug interaction is not expected with CYP4F2 inhibitor and brincidofovir coadministration."

Journal