FDA Approves Enzyvant’s Rethymic for Pediatric Congenital Athymia

The U.S. Food and Drug Administration approved Enzyvant’s Rethymic as a one-time regenerative tissue-based therapy for immune reconstitution in children born without a thymus.

With the approval, the FDA awarded Enzyvant a Priority Review Voucher under the Rare Pediatric Disease Program.

Known as pediatric congenital athymia, the ultra-rare condition has an estimated incidence of about 17 to 24 live births each year in the United States. 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. Children born without a thymus therefore have profound immunodeficiency, life-threatening immune dysregulation, and high susceptibility to potentially fatal infections. With only supportive care, these children 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.

“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, a wholly-owned subsidiary of Sumitomo Dainippon Pharma.

Rethymic (allogeneic processed thymus tissue-agdc) is the first and only treatment approved by the FDA for immune reconstitution in pediatric patients with congenital athymia. It is engineered human thymus tissue designed to regenerate the thymic function children with congenital athymia are missing and does not require donor-recipient matching.

The approval was based on the ten prospective single-arm, open-label studies with patient enrollment from 1993 to 2020 that 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-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 were 77 percent at one year and 76 percent at two years. For patients who were alive at one year post implantation, the Kaplan-Meier estimated long-term survival rate was 94 percent 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.

The most common adverse reactions (incidence in at least 10 percent of patients) reported following administration of Rethymic were hypertension (high blood pressure), cytokine release syndrome, rash, hypomagnesemia (low magnesium), renal impairment / failure (decrease of kidney function), thrombocytopenia (low platelets), and graft versus host disease. Of the 105 patients in the clinical trials, 29 patients died after receiving Rethymic, including 23 deaths in the first year 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 two deaths due to cardiorespiratory arrest. Of the six patients who died more than one-year post-implantation, the deaths were considered unrelated to study treatment: two died due to respiratory failure and one died due to each of the following: cardiopulmonary arrest, intracranial hemorrhage, infection, and unknown cause.

The FDA granted Rethymic Regenerative Medicine Advanced Therapy (RMAT), Breakthrough Therapy, Rare Pediatric Disease, and Orphan Drug designations. The European Medicines Agency also granted it Orphan Drug designation and the Advanced Therapy Medicinal Product (ATMP) designation.

Photo: Rachelle Jacques, CEO of Enzyvant

Author: Rare Daily Staff