Benzinga | Aug 4, 2021 09:51AM EDT

Myovant Highlights Results From Trials Of Enzyvant's RVT-802 Were Published In 'The Journal Of Allergy, Clinical Immunology'

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. and BASEL, Switzerland, Aug. 04, 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.

1 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

2 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

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 na?ve 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 na?ve 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.