Enzyvant Announces Publication of Positive Clinical Data in Pediatric Patients with Congenital Athymia Treated with Investigational RVT-802 (allogeneic processed thymus tissue-agdc)

Kaplan-Meier Estimated Survival One Year and Two Years After Treatment with RVT-802 for Study was 77% and 76%, respectively

Follow-up duration in the Efficacy Analysis Set (EAS) ranged from 0 to 25.5 years; For patients alive one year after 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 that occurred in patients treated with RVT-802 for investigation were low platelets, neutropenia, fever, protein in urine, hair loss, and wound dehiscence.

CAMBRIDGE, Mass. and BASEL, Switzerland, Aug. 4, 2021 (GLOBE NEWSWIRE) — Positive clinical trial results of Enzyvant’s investigational RVT-802 (allogeneic modified thymic tissue-agdc), engineered human thymic tissue implanted in 105 pediatric patients, were published today in The Journal of Allergy and Clinical Immunology

“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 health care providers and others who have enabled research into this regenerative therapy,” said Louise. Markert, MD, Ph.D., principal investigator for RVT-802 clinical trials and professor of pediatrics and immunology at Duke University School of Medicine. “These data suggest we are on the brink of a better day for pediatric patients with congenital athymia.”

Congenital athymia in children is extremely rare, with an estimated incidence in the US of ~17 to 24 live births per year.2 Children with this condition are born without a thymus, leading to severe immunodeficiency, life-threatening immune dysregulation and high susceptibility to potentially fatal infections. With only supportive care, children with congenital athymia usually die by age two or three. There are currently no FDA-approved treatments for congenital athymia.

“With evidence of long-term survival of up to 25.5 years and a study group of 105 patients, RVT-802 is unique in research 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 childhood congenital athymia are testament to the extraordinary vision of Dr. Louise Markert and the tireless efforts of the Duke University Medical Center team.”

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Engineered human thymic tissue has been studied by researchers in 10 clinical trials at a single center for more than 25 years. RVT-802 clinical trials at Duke University Medical Center are supported with funding from Enzyvant.

1 M. Louise Markert, Stephanie E. Gupton, Elizabeth A. McCarthy, Experience with cultured thymic 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
2 Hsieh, EWY, Kim-Chang, JJ, 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

Ten prospective single-arm, open-label studies with patient enrollment from 1993 to 2020 form the basis of the study dataset RVT-802. One hundred and five patients were surgically implanted with RVT-802 according to one of 10 protocols approved by the Institutional Review Board (IRB). 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 studies after implantation with RVT-802 to detect naive 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, the survival rates estimated by Kaplan-Meier (95% CI) were 77% (67.0-84.4) at one year and 76% (65.7-83.4) at two years. For patients alive one year after implantation, the long-term survival rate estimated by Kaplan-Meier was 93% with a median follow-up of 10.9 years. Patients in the clinical trials started out with very few naive T cells, but those who survived up to a year after implantation developed mature and naive T cell levels sufficient to fight infection and support survival.

To investigate the number of infections over time after RVT-802 treatment for investigation, the number of infections during the first six months after implant was analyzed and compared with the number of infections during the second six months after implant. In the second half of the year there was a significant decrease (p<.001) in the number of infections. The number of infections was 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) at year two after implantation.

The most common adverse reactions (incidence in at least two patients) reported following investigational RVT-802 implantation were thrombocytopenia, neutropenia, pyrexia (fever), proteinuria, alopecia, wound dehiscence (wound reopening), Coombs positive haemolytic anaemia, autoimmune haemolytic anaemia, haemolysis, rash, decrease in blood bicarbonate, 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 were 13 deaths from infection or complications from infection, five deaths from respiratory failure/hypoxia, three deaths from bleeding-related events, and one death from cardiorespiratory arrest. Of the six patients who died more than a year after implantation, two died from respiratory failure and one died from each of the following conditions: cardiac arrest, intracranial hemorrhage, infection, and unknown cause.

About the thymus and congenital athymia

The “T” in T cell stands for thymus because it is where T cells are selected to fight infection or destroyed if they have the potential to attack the body rather than invaders. Congenital athymia is an extremely rare condition in which children are born without a thymus, causing severe immune deficiency, vulnerability to potentially fatal infections and life-threatening immune dysregulation. With only supportive care, children with congenital athymia usually 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 US states. SCID and congenital athymia are both primary immunodeficiency disorders, but they are different conditions. The estimated incidence of congenital athymia in children in the United States is 17 to 24 live births per year

About Investigational RVT-802

Investigational RVT-802 is a novel one-time tissue-based regenerative therapy used for immune reconstruction in pediatric patients with congenital athymia. It has been studied for more than 25 years by researchers at Duke University Medical Center in 10 clinical trials. Investigational RVT-802 is engineered human thymic tissue designed to regenerate thymic function that children with congenital athymia lack and does not require donor-recipient matching. Investigational RVT-802 has received multiple designations from the U.S. Food and Drug Administration (FDA), including Regenerative Medicine Advanced Therapy (RMAT), Breakthrough Therapy, Rare Pediatric Disease, and Orphan Drug. The RVT-802 Biologics Licensing Application (BLA) has been 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.

About Enzyvant

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 main asset is its tissue-based regenerative therapy, RVT-802, for congenital athymia, an extremely rare and life-threatening pediatric immunodeficiency disorder. 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 fully owns Urovant, Enzyvant, Spirovant and Altavant. Sumitovant’s promising pipeline consists of early to late stage investigational drugs for a range of disease areas targeting high unmet need. Sumitovant is a wholly owned subsidiary of Sumitomo Dainippon Pharma. For more information about Sumitovant, visit https://www.sumitovant.com. Follow Sumitovant on LinkedIn.

About Sumitomo Dainippon Pharma Co., Ltd.
Sumitomo Dainippon Pharma ranks among the top ten publicly traded pharmaceutical companies in Japan and operates globally in key pharmaceutical markets, including Japan, the US, China and the European Union. Sumitomo Dainippon Pharma is based on the 2005 merger 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 the company website at https://www.ds-pharma.com/.

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