Kaplan-Meier estimated survival at one year and two years post treatment with investigational RVT-802 was 77% and 76%, respectively
Follow-up time in the Efficacy Analysis Set (EAS) ranged from 0 to 25.5 years; For patients who were alive at one year post treatment, the Kaplan-Meier estimated long-term survival rate was 93% at a median follow-up time of 10.9 years
The most common (>3%) adverse reactions occurring in patients treated with investigational RVT-802 were low platelets, neutropenia, fever, protein in the urine, hair loss, and wound dehiscence
CAMBRIDGE, Mass. & BASEL, Switzerland, August 4, 2021 (GLOBE NEWSWIRE) – Positive results from clinical trials of Enzyvant’s investigational RVT-802 (allogeneic processed thymus tissue-agdc), engineered human thymus tissue implanted in 105 pediatric patients, were published today in The Journal of Allergy and Clinical Immunology.1
“Families battling congenital athymia have been the heart and soul of the RVT-802 clinical trial program for more than two decades and I am deeply grateful to them, as well as the healthcare practitioners and others who have made investigation of this regenerative therapy possible,” said Louise Markert, M.D., Ph.D., principal investigator for RVT-802 clinical trials and Professor of Pediatrics and Immunology at the Duke University School of Medicine. “These data suggest we are on the threshold of a brighter day for pediatric patients with congenital athymia.”
Pediatric congenital athymia is ultra-rare with an estimated incidence in the U.S. of ~17 to 24 live births each year.2 Children who have this condition are born without a thymus, which leads to profound immunodeficiency, life-threatening immune dysregulation, and high susceptibility to potentially fatal infections. With only supportive care, children with congenital athymia typically die by age two or three. There are currently no FDA-approved treatments for congenital athymia.
“With evidence of long-term survival up to 25.5 years and a study group of 105 patients, investigational RVT-802 is unique among regenerative medicine candidates for ultra-rare diseases,” said Rachelle Jacques, CEO of Enzyvant. “The scope and quality of these data underlying RVT-802 for pediatric congenital athymia are testaments to the extraordinary vision of Dr. Louise Markert and the tireless efforts of the Duke University Medical Center team.”
Engineered human thymus tissue has been studied by researchers across 10 clinical studies at a single center for more than 25 years. RVT-802 clinical trials at Duke University Medical Center have been supported with funding from Enzyvant.
Ten prospective single-arm, open-label studies with patient enrollment from 1993 to 2020 form the basis of the investigational RVT-802 data set. One hundred and five patients were surgically implanted with RVT-802 under one of 10 Institutional Review Board (IRB)-approved protocols. Ninety-five patients were included in the Efficacy Analysis Set (EAS) and 105 patients were included in the Safety Analysis Set.
Patients were tested in clinical trials after implantation with RVT-802 to detect naïve T cells using flow cytometry at three, six, and 12 months. Survival rates were analyzed with the longest follow-up period of 25.5 years. In the EAS, Kaplan-Meier estimated survival rates (95% CI) were 77% (67.0–84.4) at one year and 76% (65.7–83.4) at two years. For patients who were alive at one year post implantation, the Kaplan-Meier estimated long-term survival rate was 93% at a median follow-up time of 10.9 years. Patients in the clinical trials started out with very few naive T cells but those who survived to one year after implantation developed mature and naïve T-cell levels sufficient to fight infection and support survival.
To explore the number of infections over time following treatment with investigational RVT-802, the number of infections were analyzed for the first six months post implantation and compared to the number of infections in the second six months after implantation. There was a significant decrease (p<.001) in the number of infections in the second six months. The number of infections were also compared between the first and second year after implantation with similar results. There was a significant decrease in the number of infections (p<.001) in year two after implantation.
The most common adverse reactions (incidence in at least two patients) reported following implantation with investigational RVT-802 were thrombocytopenia, neutropenia, pyrexia (fever), proteinuria, alopecia, wound dehiscence (wound re-opening), Coombs-positive hemolytic anemia, autoimmune hemolytic anemia, hemolysis, rash, blood bicarbonate decrease, diarrhea, and autoimmune hepatitis. Of the 105 patients, 28 patients died after receiving RVT-802, including 22 deaths in the first year (< 365 days) after implantation. Causes of death in the first year included 13 deaths due to infection or complications due to infection, five deaths due to respiratory failure/hypoxia, three deaths due to hemorrhage-related events, and one death due to cardiorespiratory arrest. Of the six patients who died more than one year post implantation, two died due to respiratory failure and one died due to each of the following: cardiopulmonary arrest, intracranial hemorrhage, infection, and unknown cause.
 M. Louise Markert, Stephanie E. Gupton, Elizabeth A. McCarthy, Experience with cultured thymus tissue in 105 children,
Journal of Allergy and Clinical Immunology, 2021, ISSN 0091-6749. https://www.sciencedirect.com/science/article/abs/pii/S0091674921010563?dgcid=author
 Hsieh, E.W.Y., Kim-Chang, J.J., Kulke, S. et al. Defining the Clinical, Emotional, Social, and Financial Burden of Congenital Athymia. Adv Ther (2021). https://doi.org/10.1007/s12325-021-01820-9
About the Thymus and Congenital Athymia
The “T” in T cell stands for thymus because it is where T cells are selected to fight infections or are destroyed if they have the potential to attack the body instead of invaders. Congenital athymia is an ultra-rare condition in which children are born without a thymus, causing profound immunodeficiency, vulnerability to potentially fatal infections, and life-threatening immune dysregulation. With only supportive care, children with congenital athymia typically die by age two or three. Congenital athymia is initially detected by T-cell deficiency observed in newborn screening for SCID (severe combined immune deficiency), which is now required in all 50 U.S. states. SCID and congenital athymia are both primary immunodeficiency disorders but they are distinct conditions. The estimated incidence of pediatric congenital athymia in the United States is 17 to 24 live births each year.2
About Investigational RVT-802
Investigational RVT-802 is a novel one-time, tissue-based regenerative therapy used for immune reconstitution in pediatric patients with congenital athymia. It has been studied by researchers at Duke University Medical Center across 10 clinical studies for more than 25 years. Investigational RVT-802 is engineered human thymus tissue designed to regenerate the thymic function that children with congenital athymia are missing and does not require donor-recipient matching. Investigational RVT-802 has been granted multiple U.S. Food and Drug Administration (FDA) designations including Regenerative Medicine Advanced Therapy (RMAT), Breakthrough Therapy, Rare Pediatric Disease, and Orphan Drug. The RVT-802 Biologics Licensing Application (BLA) was resubmitted this year and the expected action date provided by the FDA under the Prescription Drug User Fee Act (PDUFA) is October 8, 2021. The European Medicines Agency (EMA) has granted Orphan Drug designations and the Advanced Therapy Medicinal Product (ATMP) designation for RVT-802.
Enzyvant, a wholly owned subsidiary of Sumitovant Biopharma Ltd. (wholly owned by Sumitomo Dainippon Pharma Co., Ltd.), is a biotechnology company dedicated to developing novel, transformative regenerative therapies for people with devastating rare diseases. Enzyvant’s lead asset is the investigational tissue-based regenerative therapy, RVT-802, for congenital athymia, an ultra-rare and life-threatening pediatric immunodeficiency. For more information about Enzyvant, visit Enzyvant.com. Follow @Enzyvant on Twitter, Facebook, and LinkedIn.
About Sumitovant Biopharma Ltd.
Sumitovant is a global biopharmaceutical company with offices in New York City and London. Sumitovant is the majority shareholder of Myovant (NYSE: MYOV) and wholly owns Urovant, Enzyvant, Spirovant, and Altavant. Sumitovant’s promising pipeline is comprised of early-through late-stage investigational medicines across a range of disease areas targeting high unmet need. Sumitovant is a wholly owned subsidiary of Sumitomo Dainippon Pharma. For further information about Sumitovant, please visit https://www.sumitovant.com. Follow Sumitovant on LinkedIn.
About Sumitomo Dainippon Pharma Co., Ltd.
Sumitomo Dainippon Pharma is among the top-ten listed pharmaceutical companies in Japan, operating globally in major pharmaceutical markets, including Japan, the U.S., China and the European Union. Sumitomo Dainippon Pharma is based on the merger in 2005 between Dainippon Pharmaceutical Co., Ltd., and Sumitomo Pharmaceuticals Co., Ltd. Today, Sumitomo Dainippon Pharma has more than 7,000 employees worldwide. Additional information about Sumitomo Dainippon Pharma is available through its corporate website at https://www.ds-pharma.com/.