peboctocogene camaparvovec (DTX201) / Ultragenyx - LARVOL DELTA

Co-Packaged Genomic DNA in AAV Particles is Not Detected in Animal Tissues After Systemic Administration (ASGCT 2024) - "Importantly, HPV18 sequences were undetectable in vivo from mouse tissues extracted from multiple organs following intravenous delivery of DTX201. Taken together, these data support the safety of manufacturing high-quality gene therapy products such as DTX201 in PCLs derived from HeLa S3 cells."

Cervical Cancer • Gene Therapies • Hematological Disorders • Hemophilia • Oncology • Rare Diseases • Solid Tumor

First-in-Human Dose-Finding Study of AAVhu37 Vector-Based Gene Therapy: BAY 2599023 Has Stable and Sustained Expression of FVIII over 2 Years (ASH 2021) - P1/2 | "Of the 9 patients treated, 5 patients developed an AESI: mild/moderate alanine aminotransferase (ALT) elevations observed in Cohort 2 (n =1) and Cohort 3 (n = 3) were managed with corticosteroid treatment; another ALT elevation was reported as study-drug-related SAE in Cohort 3 (n = 1) but returned to normal a few weeks after interruption of the H2 blocker famotidine. Conclusions BAY 2599023 was designed to enhance efficacy and durability of FVIII expression with a favorable safety profile. Sustained FVIII levels allowed suspension of FVIII prophylaxis in the majority of patients, with asymptomatic ALT elevations that responded to corticosteroids, making BAY 2599023 a key candidate in the evolution of gene therapy in hemophilia A."

P1 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

[VIRTUAL] First-in-Human Gene Therapy Study of AAVhu37 Capsid Vector Technology in Severe Hemophilia A – BAY 2599023 has Broad Patient Eligibility and Stable and Sustained Long-Term Expression of FVIII (ASH 2020) - P1/2 | "BAY 2599023 has a good safety profile, with the potential to achieve endogenous expression of FVIII at therapeutic levels over an extended period. Successful proof-of-concept has been achieved, with measurable and sustained expression of endogenous FVIII."

Clinical • P1 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

First-in-human Gene Therapy Study of AAVhu37 Capsid Vector Technology in Severe Hemophilia A (ASH 2019) - P1/2; "BAY 2599023 was previously shown in non-clinical studies to have a good safety profile, with the potential to achieve endogenous expression of FVIII at therapeutic levels, over an extended period of time. In this first-in-human clinical study with BAY 2599023, two patients have been treated with BAY 2599023 at the starting dose of 0.5 x 1013 GC/kg and no safety concerns have been reported to date. Measurable expression of endogenous FVIII and an early read-out of hemostatic efficacy have been demonstrated in both patients."

P1 data

Characteristics of BAY 2599023 in the Current Treatment Landscape of Hemophilia A Gene Therapy. (PubMed, Curr Gene Ther) - "Here, we introduce the characteristics of the BAY 2599023 (AAVhu37.hFVIIIco, DTX 201) gene therapy product, including the low prevalence in the general population of anti-AAV-hu37 antibodies, as well as other gene therapy AAV products and approaches. We will examine how these can potentially meet the challenges of gene therapy, with the ultimate aim of improving the lives of patients with hemophilia A."

Journal • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Study to Test the Safety and How Well Patients With Severe Hemophilia A Respond to Treatment With BAY 2599023 (DTX 201), a Drug Therapy That Delivers a Healthy Version of the Defective Factor VIII Gene Into the Nucleus of Liver Cells Using an Altered, Non-infectious Virus (AAV) as a "Shuttle". (clinicaltrials.gov) - P1/2 | N=11 | Active, not recruiting | Sponsor: Bayer | Recruiting ➔ Active, not recruiting | N=30 ➔ 11

Enrollment change • Enrollment closed • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Study to Test the Safety and How Well Patients With Severe Hemophilia A Respond to Treatment With BAY 2599023 (DTX 201), a Drug Therapy That Delivers a Healthy Version of the Defective Factor VIII Gene Into the Nucleus of Liver Cells Using an Altered, Non-infectious Virus (AAV) as a "Shuttle". (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Bayer | Trial completion date: Jun 2027 ➔ Nov 2026 | Trial primary completion date: May 2027 ➔ Nov 2026

Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

ULTRAGENYX PHARMACEUTICAL INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) (Market Screener) - "DTX201 is a Factor VIII gene therapy program for the treatment of hemophilia A....The first three cohorts with two patients each have been dosed using material from our proprietary manufacturing platform. Enrollment of additional dose cohorts in the Phase 1/2 study is currently ongoing."

Enrollment status • Gene Therapies • Hemophilia

"In any case, the DMC has cleared dosing with the highest dose, 4x10^13vg/kg, of BAY 2599023 #ISTH2021" (@ByMadeleineA)

[VIRTUAL] Evolution of AAV Vector Gene Therapy is Ongoing In Hemophilia. Will the Unique Features of BAY 2599023 Address the Outstanding Needs? (ISTH 2021) - P1/2 | "Conclusions : BAY 2599023 was designed to enhance efficacy and durability of FVIII expression with a favorable safety profile. All patients with evaluable data have shown effective, sustained FVIII levels, with no SAEs, making BAY 2599023 a key candidate in the evolution of gene therapy in hemophilia A."

Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

"＜#ISTH2021 報告＞ #Bayer/#Ultragenyx 社の #第VIII因子 を発現させる #血友病A遺伝子治療薬 #BAY2599023 の結果が発表されたが、血中の第VIII因子レベルは納得がいくものではななかった。今後最高用量での治験が開始されるため、その結果が待たれる。 https://t.co/oTUxtnZPTu #エバリュエート" (@EvaluateJP)

Study to Test the Safety and How Well Patients With Severe Hemophilia A Respond to Treatment With BAY 2599023 (DTX 201), a Drug Therapy That Delivers a Healthy Version of the Defective Factor VIII Gene Into the Nucleus of Liver Cells Using an Altered, Non-infectious Virus (AAV) as a "Shuttle". (clinicaltrials.gov) - P1/2; N=30; Recruiting; Sponsor: Bayer; Trial completion date: Dec 2026 ➔ Jun 2027; Trial primary completion date: Oct 2022 ➔ May 2027

Clinical • Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Generation Bio Presents Preclinical Data Demonstrating Broad Potential of Gene Therapy Platform at ASGCT and Reports First Quarter Financial Results (Yahoo Finance) - "Generation Bio...today reported data from multiple digital presentations during the ongoing 24th American Society of Gene and Cell Therapy (ASGCT) Annual Meeting as well as first quarter 2021 financial results....Highlights from Digital Presentations at ASGCT: Novel non-viral gene therapy unlocks significant potential for genetic medicine...Construct optimization improves potency of ctLNP-ceDNA in mouse models of hemophilia A..."

Preclinical • Hemophilia

[VIRTUAL] First-in-Human Gene Therapy Study of BAY 2599023 in Severe Hemophilia A: Long-Term Safety and FVIII Activity Results (ASGCT 2021) - P1/2 | "In this first-in-human study, six patients were treated with escalating doses of BAY 2599023. Mild to moderate elevations of ALT, managed with corticosteroids, were the only observed AEs related to BAY 2599023. Sustained expression of endogenous FVIII was observed in all patients with indications of hemostatic efficacy."

Clinical • P1 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

[VIRTUAL] BROAD PATIENT ELIGIBILITY AND LONG‐TERM TOLERABILITY IN THE FIRST‐IN‐HUMAN GENE THERAPY STUDY OF BAY 2599023 IN SEVERE HAEMOPHILIA A (EAHAD 2021) - P1/2 | "BAY 2599023 has broad eligibility in patients with haemophilia A due to low seroprevalence of NAbs and ADA against AAVhu37, compared with other AAVs. BAY 2599023 has a good safety profile, and measurable and sustained expression of endogenous FVIII."

Clinical • P1 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Study to Test the Safety and How Well Patients With Severe Hemophilia A Respond to Treatment With BAY 2599023 (DTX 201), a Drug Therapy That Delivers a Healthy Version of the Defective Factor VIII Gene Into the Nucleus of Liver Cells Using an Altered, Non-infectious Virus (AAV) as a "Shuttle". (clinicaltrials.gov) - P1/2; N=30; Recruiting; Sponsor: Bayer; Trial completion date: Jul 2026 ➔ Nov 2026; Trial primary completion date: May 2022 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

[VIRTUAL] First-in-Human Gene Therapy Study of AAVhu37 Capsid Vector Technology in Severe Hemophilia A: Safety and FVIII Activity Results (ISTH 2020) - P1/2 | "Six patients were treated with BAY 2599023 at doses of 0.5, 1.0 and 2.0 × 1013 GC/kg. Successful proof-of-concept has been achieved with measurable, stable expression of endogenous FVIII and indications of hemostatic efficacy in all treated patients."

Clinical • P1 data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Study to Test the Safety and How Well Patients With Severe Hemophilia A Respond to Treatment With BAY 2599023 (DTX 201), a Drug Therapy That Delivers a Healthy Version of the Defective Factor VIII Gene Into the Nucleus of Liver Cells Using an Altered, Non-infectious Virus (AAV) as a "Shuttle". (clinicaltrials.gov) - P1/2; N=30; Recruiting; Sponsor: Bayer; Trial completion date: Jul 2025 ➔ Jul 2026; Trial primary completion date: Jan 2022 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date • Gene Therapies • Genetic Disorders • Hematological Disorders • Hemophilia • Rare Diseases

Study to Test the Safety and How Well Patients With Severe Hemophilia A Respond to Treatment With BAY 2599023 (DTX 201), a Drug Therapy That Delivers a Healthy Version of the Defective Factor VIII Gene Into the Nucleus of Liver Cells Using an Altered, Non-infectious Virus (AAV) as a "Shuttle". (clinicaltrials.gov) - P1/2; N=30; Recruiting; Sponsor: Bayer; Trial primary completion date: Mar 2021 ➔ Jan 2022

Clinical • Trial primary completion date

Ultragenyx Pharmaceutical Inc (RARE) Q4 2019 earnings call transcript (The Motley Fool) - "I'll discuss is DTX201 for hemophilia A...At the European Association of hemophilia and Allied Disorders meeting last week, Bayer presented data on first two low dose Cohorts of the Phase 1/2 study. All four patients showed a response with three of the four patients showing clinically meaningful increase in Factor VIII levels....A third high-dose Cohort has been dosed and we expect to see additional updates this year. Bayer is responsible for the clinical execution of this program...As a reminder, we are eligible to see milestones and royalty payments from Bayer for this program."

Clinical • P1/2 data • Trial status

FIRST‐IN‐HUMAN GENE THERAPY STUDY OF AAVHU37 CAPSID VECTOR TECHNOLOGY IN SEVERE HAEMOPHILIA A: SAFETY AND FVIII ACTIVITY RESULTS (EAHAD 2020) - P1/2; "In this first-in-human study, two patients were treated with BAY 2599023 at the starting dose of 0.5 × 1013 GC/kg and no safety concerns were reported. There was measurable expression of endogenous FVIII and early indications of haemostatic efficacy in both patients. The data generated from this first-dose cohort demonstrate successful translation from preclinical to clinical development and proof-of-mechanism for BAY 2599023."

Clinical • P1 data

The future of hemophilia A treatment: From Jivi® to gene therapy (EAHAD 2020) - "Join us for a review of the latest Jivi® (damoctocog alfa pegol) data from the PROTECT VIII study; learn about breaking head-to-head data; and explore the first clinical data from Bayer’s gene therapy, BAY 2599023. This meeting has been organized and funded by Bayer."

Factor VIII Gene Therapy Study in Patients With Hemophilia A (clinicaltrials.gov) - P1/2; N=30; Recruiting; Sponsor: Bayer; N=18 ➔ 30

Clinical • Enrollment change