TransVax (ASP0113) / Astellas, Fresh Tracks Therap - LARVOL DELTA

"She’s TransVax!" (@Jessica29257744)

"I am in a control group. But if I wasn't then I would totally be transvaxxed. Sure, why not? https://t.co/sdg1fjkG4e" (@aquariyesss)

A Study to Evaluate a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT) (clinicaltrials.gov) - P3 | N=514 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Active, not recruiting ➔ Completed

Trial completion • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Cytomegalovirus Infection • Hematological Malignancies • Myelodysplastic Syndrome • Transplantation

"Lol, you’re a Transvax just like me." (@andy798001)

A randomised, placebo-controlled phase 3 study to evaluate the efficacy and safety of ASP0113, a DNA-based CMV vaccine, in seropositive allogeneic haematopoietic cell transplant recipients. (PubMed, EClinicalMedicine) - P3 | "Safety findings were similar between groups. Astellas Pharma Global Development, Inc ."

Clinical • Journal • P3 data • Cytomegalovirus Infection • Transplantation

Vical and Astellas announce topline results from a phase 2 study of investigational cytomegalovirus (CMV) vaccine (ASP0113) in kidney transplant patients (Vical Press Release) - P2, N=150; "Results from the study demonstrated that the trial did not meet its primary endpoint, which was the proportion of patients having CMV viremia defined as a plasma viral load of ≥ 1000 IU/mL by central laboratory assay through one year after first injection of study drug...look forward to the results from the pivotal Phase 3 study in HCT recipients, which we expect to obtain during the fourth quarter of 2017..."

Anticipated P3 data • P2 data • Cytomegalovirus Infection • Graft versus Host Disease

Vical reports second quarter 2017 financial and operational results (Vical Press Release) - "The multinational Phase 3 registration trial in HCT recipients completed enrollment in September 2016...Astellas expects top-line data to be available in the first quarter of 2018. Vicaland Astellas continue to make progress towards a potential BLA filing in 2018. Assuming a successful trial outcome, Astellas intends to commercialize ASP0113 in North America, Europe, and Asia."

BLA • Launch • P3 data • Cytomegalovirus Infection • Graft versus Host Disease

Vical: Stifel Healthcare Conference (Vical) - "Phase 2 data support reduction in mortality"; "Reduction in CMV Viremia"; "Virologic Endpoints"

P2 data

Vical: Q1 FY 2016 Results (Vical) - Anticipated BLA filing in hematopoietic cell transplant in 2018

Anticipated BLA • Cytomegalovirus Infection

An Evaluation of a Cytomegalovirus (CMV) Vaccine (ASP0113) in CMV-Seropositive and CMV-Seronegative Healthy Subjects and CMV-Seronegative Dialysis Patients (clinicaltrials.gov) - P1; N=48; Completed; Sponsor: Astellas Pharma Global Development, Inc.; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Cytomegalovirus Infection • Immunology

Astellas and Vical announce top-line results for phase 3 trial of cytomegalovirus vaccine ASP0113 in hematopoietic stem cell transplant recipients (Astellas Press Release) - P3, N=514; HELIOS; Sponsor Astellas Pharma; "Astellas Pharma...announced today that ASP0113...did not meet its primary or secondary endpoints in the Phase 3 HELIOS clinical trial. The vaccine was generally well tolerated, with injection-site reactions being the most commonly reported adverse event...results did not demonstrate a significant improvement in overall survival and reduction in CMV end-organ disease."

P3 data: top line • Graft versus Host Disease

A Study to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seronegative Kidney Transplant Recipients Receiving an Organ From a CMV-Seropositive Donor (clinicaltrials.gov) - P2; N=150; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Completed ➔ Active, not recruiting

Enrollment closed • Biosimilar • Cytomegalovirus Infection • Immunology

ASP0113: Anticipated patent expiry in US, Europe, Canada and Japan related to codon-optimized polynucleotide-based vaccine against human CMV infection between December 19, 2023 and May 12, 2025 (Vical) - Annual Report 2016

Patent expiry • Cytomegalovirus Infection

Astellas: Q2 FY 2016 Results (Astellas) - Discontinued in US and Europe for Cytomegalovirus infection or reactivation in solid organ transplant recipients since the phase 2 study did not meet its primary endpoint

Discontinued • Cytomegalovirus Infection

ASP0113 Elicits an Immune Response in CMV-Seronegative Dialysis Patients: Comparison to Healthy Subjects. (ATC 2017) - "ASP0113 was well tolerated. B-cell responses were undetectable, while T cell responses were demonstrated in both H- and D- subjects."

Adverse events • Biosimilar • Cytomegalovirus Infection • Graft versus Host Disease • Immunology • Pain

A Study to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seronegative Kidney Transplant Recipients Receiving an Organ From a CMV-Seropositive Donor (clinicaltrials.gov) - P2; N=140; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial primary completion date: Apr 2017 ->Jun 2016

Trial primary completion date • Biosimilar

Vical Incorporated net loss declines in 3Q2015 (Financial Trends) - "...enrollment process in the multinational Phase III registrational study in nearly five-hundred hematopoietic cell transplant recipients is underway...It projects enrollment in the study to be completed by 3Q2016, with the top-line report being available in the last quarter of 2017."

Anticipated enrollment status • Anticipated P3 data: top line • Cytomegalovirus Infection

Pharmacokinetics and Immunogenicity of ASP0113 in CMV-Seronegative Dialysis Patients and CMV-Seronegative and -Seropositive Healthy Subjects. (PubMed, Clin Pharmacol Drug Dev) - "No serious adverse events occurred; the most common adverse event in ASP0113-vaccinated patients was injection-site pain (64.9%). Some CMV-seronegative healthy subjects and dialysis patients had T-cell responses; no humoral responses were detected."

Clinical • Journal • PK/PD data

A randomized, phase 2 study of ASP0113, a DNA-based vaccine, for the prevention of CMV in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. (PubMed, Am J Transplant) - P2; "Transplant recipients were randomized (1:1) to receive 5 doses of ASP0113 (5 mg; n = 75) or placebo (n = 74) on Days 30/60/90/120/180 posttransplant, and they received prophylactic valganciclovir/ganciclovir 10-100 days posttransplant. There were similar numbers of transplant recipients with treatment-emergent adverse events between groups; however, more transplant recipients reported injection site pain in the ASP0113 group compared with placebo. ASP0113 did not demonstrate efficacy in the prevention of CMV viremia in this CMV-seronegative kidney transplant population, but demonstrated a safety profile similar to placebo."

Clinical • Journal • P2 data

A Study to Evaluate a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT) (clinicaltrials.gov) - P3; N=514; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial completion date: Nov 2020 ➔ Mar 2022

Trial completion date

A RANDOMISED, PLACEBO-CONTROLLED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ASP0113, A FIRST-IN-CLASS, DNA-BASED VACCINE IN CMV-SEROPOSITIVE ALLOGENEIC HAEMATOPOIETIC CELL TRANSPLANT RECIPIENTS (EBMT 2019) - P3; "ASP0113 did not demonstrate efficacy in the reduction of overall mortality and CMV EOD through 1 year post transplant. ASP0113 demonstrated a similar safety profile to placebo, with the exception of injection site-related TEAEs that were more frequent in the ASP0113 group. Participants in this study will be followed up to 5.5 years post transplant for long-term safety assessments."

Clinical • P3 data

A Study to Evaluate a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT) (clinicaltrials.gov) - P3; N=514; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial completion date: Mar 2020 ➔ Nov 2020

Clinical • Trial completion date

"#TCTM19 Forman: vaccinia delivery of CMV protein will potentially be useful for all without specific HLA restriction; currently in multicenter study. (Hopefully it works, because Astellas CMV DNA vaccine (ASP0113) study was unfortunately negative.)" (@hemedoc)

Clinical