Enzyvant announced the US Food and Drug Administration (FDA) approval of Rethymic (allogeneic processed thymus tissue-agdc), a one-time regenerative tissue-based therapy for immune reconstitution in pediatric patients with congenital athymia.
“For too long, families have faced a reality that the brutal journey for pediatric congenital athymia patients receiving supportive care only would end tragically. The FDA approval of Rethymic will help patients access this desperately needed therapy beyond clinical study,” said Rachelle Jacques, CEO of Enzyvant. “We are deeply grateful to the 105 patients who participated in clinical trials, their families, and all of the stakeholders who contributed to this pioneering regenerative medicine research programme.”
Pediatric congenital athymia is ultra-rare with an estimated incidence of about 17 to 24 live births each year in the United States. Children who have this condition are born without a thymus and therefore have 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.
“This therapy is the result of more than 25 years of research aimed at increasing survival for patients who previously had very little hope,” said Louise Markert, M.D, Ph.D., principal investigator for Rethymic clinical trials and Professor of Pediatrics and Immunology at the Duke University School of Medicine. “Our research program was inspired each and every day by the possibilities that exist for children who have congenital athymia with an FDA-approved treatment for this devastating condition.”
With this FDA approval, Enzyvant has obtained a Priority Review Voucher (PRV) under the Rare Pediatric Disease Programme.
Ten prospective single-arm, open-label studies with patient enrollment from 1993 to 2020 form the basis of the Rethymic data set. One hundred and five patients were surgically implanted with Rethymic 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.
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% (0.670–0.841) at one year and 76% (0.658–0.832) at two years. For patients who were alive at one year post implantation, the Kaplan-Meier estimated long-term survival rate was 94% at a median follow-up time of 10.7 years. For the patients in the clinical trials, naïve T-cell levels were measured using flow cytometry at six, 12, and 24 months after implantation with Rethymic. Patients in the clinical trials started out with very few naïve T cells but naïve CD4+ and CD8+ T cells began to reconstitute over the first year, with a durable increase through year two. Reductions in the number of infections over time during the first two years after treatment were statistically significant (p<0.001).
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 US 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.
Rethymic (allogeneic processed thymus tissue-agdc) is a novel one-time tissue-based regenerative therapy used for immune reconstitution in pediatric patients with congenital athymia. Rethymic is engineered human thymus tissue designed to regenerate the thymic function children with congenital athymia are missing and does not require donor-recipient matching. Rethymic has been studied across 10 clinical trials for more than 25 years and was granted multiple US Food and Drug Administration (FDA) designations including Regenerative Medicine Advanced Therapy (RMAT), Breakthrough Therapy, Rare Pediatric Disease, and Orphan Drug. It also has been granted the Orphan Drug designation and the Advanced Therapy Medicinal Product (ATMP) designation by the European Medicines Agency (EMA). Rethymic is the first and only treatment approved by the FDA for immune reconstitution in pediatric patients with congenital athymia.