Adenoviridae Infections

In a potentially game-changing development, scientists have revealed a new understanding of sometimes fatal viral infections that affect the heart. Traditionally, the focus has been on heart inflammation known as myocarditis, which is often triggered by the body's immune response to a viral infection. However, a new study sheds new light on this notion, revealing that the virus itself creates potentially dangerous conditions in the heart before inflammation sets in. In a potentially game-changing development, scientists with the Fralin Biomedical Research Institute at VTC have revealed a new understanding of sometimes fatal viral infections that affect the heart. Traditionally, the focus has been on heart inflammation known as myocarditis, which is often triggered by the body's immune response to a viral infection. However, a new study led by James Smyth, associate professor at the Fralin Biomedical Research Institute, sheds new light on this notion, revealing that the virus itself creates potentially dangerous conditions in the heart before inflammation sets in. The discovery, now online and set to appear in the March 29 issue of Circulation Research, suggests completely new directions to diagnose and treat viral infections affecting the heart. Given the high incidence of viral-related myocarditis leading to sudden cardiac death, the insight is crucial. Up to 42 percent of sudden cardiac deaths in young adults are attributed to myocarditis, and of these cases viral infection is the leading cause. "From a clinical perspective, our understanding of viral infection of the heart has focused on inflammation, causing problems with the rate or rhythm of the heartbeat," Smyth said. "But we have found an acute stage when the virus first infects the heart and before the body's immune response causes inflammation. So even before the tissue is inflamed, the heart is being set up for arrhythmia." To make this discovery, researchers focused on adenovirus, a common culprit in cardiac infection and myocarditis, using Mouse Adenovirus Type-3 to replicate the human infection process. They found that early in the infection, the virus disrupts critical components of the heart's communication and electrical systems. As a result, even before symptoms appear, the adenoviral infection creates conditions that disrupt the heart's gap junctions and ion channels, according to virologist Rachel Padget, the study's first author who worked in the Smyth lab while completing a doctoral degree from the Virginia Tech Translational Biology, Medicine, and Health graduate program. Gap junctions are like tiny tunnels between heart cells that allow them to communicate, and ion channels are like gates in the cell membranes that help maintain the right balance of ions needed for the heart to generate normal patterns of electrical activity that allow it to beat properly. When adenoviral infection disturbs these communication bridges and gatekeepers, it creates a situation where the heart might develop irregular patterns of electrical activity called arrhythmias affecting its mechanical beating and blood pumping capacity, and that can lead to sudden cardiac problems, especially in people with active infections. Now, by targeting specific heart changes induced by viral infections at the molecular level, researchers aim to reduce the risk of cardiac issues in people grappling with viral illnesses. "Individuals who have acute infections can look normal by MRI and echocardiography, but when we delved into the molecular level, we saw that something very dangerous could occur," Smyth said. "In terms of diagnostics, we can now work with our colleagues here to start looking ways to analyze blood for a biomarker of the more serious problem. People get cardiac infections all the time and they recover. But can we identify what's different about individuals that are at a higher risk to have the arrhythmia, possibly through a simple blood test in the doctor's office." The work was supported in part by grants from the National Institutes of Health, American Heart Association, Fralin Biomedical Research Institute Seale Innovation Fund and Lyerly Postdoctoral Excellence Award.

Ferring presenting design and methodology for the ABLE-41 Real-World Evidence study at this week’s 20th Annual ASCO Genitourinary Cancers Symposium in San Francisco Study evaluating effectiveness, overall experiences, patterns of use, and safety of the first and only FDA-approved intravesical gene therapy Final results from ongoing post-marketing study are expected by the end of 2026 PARSIPPANY, N.J.--(BUSINESS WIRE)-- Ferring Pharmaceuticals announced today it is presenting the methodology for the ADSTILADRIN in BLadder cancEr (ABLE-41) Real World Evidence (RWE) study at the 20th Annual American Society of Clinical Oncologists Genitourinary Cancers Symposium (ASCO GU). ABLE-41 (NCT06026332) is an ongoing Phase 4 observational study evaluating the effectiveness, overall experiences, patterns of use, and safety of ADSTILADRIN® (nadofaragene firadenovec-vncg) in a U.S. real-world setting. ADSTILADRIN is the first and only intravesical gene therapy approved by the U.S. Food and Drug Administration (FDA) in adult patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (±Ta/T1). “Many NMIBC patients who initially respond to BCG therapy experience disease recurrence or progression, so developing a local, effective, bladder-preserving treatment option like ADSTILADRIN has long been needed,” said Kristen Litchfield, DHSc, Vice President, Medical Affairs, Uro-Oncology, Ferring Pharmaceuticals, U.S. “In our pivotal Phase 3 trial, ADSTILADRIN demonstrated long-term efficacy and tolerability starting from the first dose. With this new post-marketing study, we are looking to build an additional body of evidence in the real-world setting.” ABLE-41 is a non-interventional study following NMIBC patients aged 18 years or older who are being treated with ADSTILADRIN in a clinical setting and had not previously received this therapy in a clinical trial. In September 2023, Ferring announced the first patient enrolled in ABLE-41. Eligible patients include those who were prescribed and scheduled to receive treatment, per their physician’s discretion, or patients who received their first instillation (per physician discretion) after September 5, 2023, but before the site was activated in the trial. The primary objective is to assess whether patients achieve a complete response (CR) at three months and/or at any time within a year of their first instillation. “ABLE-41 is a unique real-world registry that will provide important evidence on what patients and physicians can expect from intravesical gene therapy in a clinical setting,” said Siamek Daneshmand, M.D., who is affiliated with USC/Norris Comprehensive Cancer Center and the University of Southern California, and a lead ABLE-41 investigator. “I am thrilled to be part of this ongoing research and among the first uro-oncologists to be treating patients with ADSTILADRIN in a clinical setting. This is an innovative therapy that is already changing how we manage NMIBC patients who no longer respond to standard BCG therapy, providing an alternative to radical cystectomy, or bladder removal surgery.” Participants in ABLE-41 will be followed for 24 months, or until study discontinuation or withdrawal. Key secondary outcomes include the following: treatment patterns of use; duration of CR; recurrence-free survival, cystectomy-free survival, progression-free survival, overall survival, and bladder cancer–specific mortality; patient, caregiver, and physician experiences; adjunctive use of molecular markers; and safety. Patient experiences will be assessed with a commonly used quality of life questionnaire (EuroQol 5 Dimension 5 Level), measuring mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Caregiver experiences will be measured with the Work Productivity and Activity Impairment questionnaire, adapted for caregiving, which assesses the impact of health problems on paid and unpaid work. Final results from this prospective, multi-institutional study are expected at the end of 2026. Learn more at . Poster Presentation Info: Trials in Progress Poster Session B: Urothelial Carcinoma “ABLE-41: Nadofaragene firadenovec-vncg early utilization and outcomes in a real-world setting in the United States.” Abstract #TPS705, Friday, Jan. 26 at 5:45 - 6:45 p.m. PST Presenters: Neal Shore, Sia Daneshmand, Kristen Litchfield, Amy Guo, Kristian Juul, Sandra Guedes, Dalila Delattre, and Yair Lotan About ADSTILADRIN ADSTILADRIN® (nadofaragene firadenovec-vncg) is the first and only FDA-approved intravesical gene-therapy for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high quantities of interferon alfa-2b protein, a naturally-occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer. ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with high-grade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849).1 About Non-Muscle Invasive Bladder Cancer (NMIBC) NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.2 Bladder cancer is the sixth most common cancer in the U.S., and it is estimated that there were approximately 81,180 new cases of bladder cancer in the U.S. in 2022,3 75% of which present as NMIBC.4 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard of care. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease.3 Current treatment options for BCG-unresponsive patients are very limited, and National Comprehensive Cancer Network (NCCN) guidelines recommend cystectomy (partial or complete removal of the bladder).5 INDICATION ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product. WARNINGS AND PRECAUTIONS: Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy. Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals. DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration. USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose. ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination). You are encouraged to report negative side effects of prescription drugs to FDA. Visit or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING. Please click to see the full Prescribing Information. About Ferring Pharmaceuticals Ferring Pharmaceuticals is a privately-owned, research-driven, specialty biopharmaceutical group committed to building families and helping people live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, and in areas of gastroenterology and orthopaedics. We are at the forefront of innovation in microbiome-based therapeutics and uro-oncology intravesical gene therapy. Our company was founded in 1950 and is headquartered in Saint-Prex, Switzerland. Ferring employs more than 7,000 people worldwide and markets its medicines in over 100 countries. Ferring USA is based in Parsippany, New Jersey, and employs more than 900 employees. For more information, please visit , call 1-888-FERRING (1-888-337-7464), or connect with us on LinkedIn, and X (Twitter). References: ADSTILADRIN in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). Gov Identifier: NCT02773849. . Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol 2021; 22: 107–17. American Cancer Society. Key Statistics for Bladder Cancer. . Updated January 13,2023. Accessed October 15, 2023. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234-41. NCCN Guideline Insights. Bladder Cancer, Version 3.2023. . Accessed November 7, 2023. More information is available at the following: Health Care Providers: If you are interested in ordering ADSTILADRIN, please sign up for information and updates at ADSTILADRINHCP.com. Patients and Consumers: For more information about ADSTILADRIN, please call 1-888-FERRING (888-337-7464), and select option number one.

PARSIPPANY, N.J.--( BUSINESS WIRE )--Ferring Pharmaceuticals today announced that ADSTILADRIN ® (nadofaragene firadenovec-vncg) is now fully available across the U.S. for healthcare providers to prescribe for their adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. Approved by the U.S. Food & Drug Administration (FDA) in December 2022, ADSTILADRIN is the first and only FDA-approved intravesical gene therapy for adults with NMIBC who no longer respond to standard therapy. “From the day we received FDA approval, Ferring has been committed to making ADSTILADRIN available to every appropriate high-risk NMIBC patient quickly and responsibly, working collaboratively with the bladder cancer community to inform our approach,” said Bipin Dalmia, Senior Vice President, Global Head, Uro-Oncology Franchise at Ferring Pharmaceuticals. “With our significant manufacturing investments, we have achieved full product supply ahead of schedule. We are therefore ending our ADSTILADRIN Early Experience Program and look forward to bringing this novel therapy to every patient who needs it.” In September 2023, Ferring initiated the ADSTILADRIN Early Experience Program to a mix of clinical trial sites that participated in the ADSTILADRIN Phase 3 study and community clinics with the highest number of appropriate patients with NMIBC. This temporary program represented Ferring’s commitment to treat as many patients as possible in the short term while ensuring every patient who started on ADSTILADRIN had the ability to continue therapy for the duration of their treatment. Now that full product supply is available ahead of schedule, Ferring can end the temporary ADSTILADRIN Early Experience Program and dramatically increase patient access. “ADSTILADRIN represents an effective alternative therapy for patients with NMIBC who, historically, had very few options once they no longer responded to standard BCG therapy,” said Andrea Maddox-Smith, CEO of the Bladder Cancer Advocacy Network, BCAN. “Increasing access to this innovative therapy offers the potential of what patients need most – safe, effective treatment options that bring hope.” Ferring also initiated a non-interventional study, known as the “ADSTILADRIN in BLadder CancEr” (ABLE-41) U.S. Real World Evidence (RWE) Study (NCT06026332). This ongoing study is exploring early utilization, experiences, and outcomes of ADSTILADRIN in the routine care setting. About ADSTILADRIN ADSTILADRIN® (nadofaragene firadenovec-vncg) is the first and only FDA-approved intravesical gene-therapy for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high quantities of interferon alfa-2b protein, a naturally-occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer. ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with high-grade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on clinicaltrials.gov: NCT02773849). 1 About Non-Muscle Invasive Bladder Cancer (NMIBC) NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body. 2 Bladder cancer is the sixth most common cancer in the U.S., and it is estimated that there were approximately 81,180 new cases of bladder cancer in the U.S. in 2022, 3 75% of which present as NMIBC. 4 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard of care. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease. 3 Current treatment options for BCG-unresponsive patients are very limited, and National Comprehensive Cancer Network (NCCN) guidelines recommend cystectomy (partial or complete removal of the bladder). 5 INDICATION ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product. WARNINGS AND PRECAUTIONS: Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy. Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals. DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration. USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose. ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination). You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING. Please click to see the full Prescribing Information . About Ferring Pharmaceuticals Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, uro-oncology and in specialty areas within gastroenterology, including microbiome therapeutics, and orthopaedics. For more information, call 1-888-FERRING (1-888-337-7464) or visit http://www.ferringusa.com/ . References: ADSTILADRIN in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). Gov Identifier: NCT02773849. https://clinicaltrials.gov/ct2/show/NCT02773849 . Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol 2021; 22: 107–17. American Cancer Society. Key Statistics for Bladder Cancer. https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html . Updated January 13,2023. Accessed October 15, 2023. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234-41. NCCN Guideline Insights. Bladder Cancer, Version 3.2023. www.nccn.org/patients/guidelines/content/PDF/bladder-patient.pdf . Accessed November 7, 2023. More information is available at the following: Health Care Providers: If you are interested in ordering ADSTILADRIN, please sign up for information and updates at ADSTILADRINHCP.com . Patients and Consumers: For more information about ADSTILADRIN, please call 1-888-FERRING (888-337-7464), and select option number one.