Regenerative Therapy for Rare Immune Disorder Receives FDA Approval

Babys lymphatic system, illustration
Illustration of a babys lymphatic system.

Enzyvant, a subsidiary of Sumitovant Biopharma, received a long-awaited FDA approval for its tissue based regenerative therapy for treatment of congenital athymia last week after almost 30 years of development.

The treatment, which is known as Rethymic, is a single use therapy that is inserted as small slices of tissue into the quadriceps muscle in the thigh. It aims to rebuild immune function in infants born without a thymus gland, a small organ in the chest where T cells are produced. No other therapies are approved for this indication.

Overall, of 105 children who received the therapy between 1993 and 2020, 76 are still alive. Children born with congenital athymia often die before the age of 3 years with only supportive care.

“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, which was sold to Sumitovant Biopharma in 2019.

Congenital athymia is very rare, affecting around 17-24 children born in the U.S. each year. These children are often diagnosed during early testing for severe combined immune deficiency (SCID) a similar, but distinct immune disorder.

Rethymic, allogeneic processed thymus tissue-agdc, is made of engineered human thymus tissue that slowly rebuilds the ability to produce T-cells in children given the implant over 6-12 months.

Duke University Hospital started enrolling patients into trials of the therapy as early as 1993 and since then 10 prospective single-arm, open-label studies of the therapy have been carried out including 105 patients in total.

Survival rates after being given the therapy were 77% at one year and 76% at two years. Notably, survival at one year seemed to predict long-term survival, as long-term survival rate after this time was 94% with a median follow up time of 10.7 years and longest follow-up time of 25.5 years.

This coincides with the time it takes the therapy to ‘activate’ in a patient’s body. It is not immediately effective with patients initially having very few T cells with numbers of CD4+ and CD8+ T cells gradually increasing over the first year and continuing to go up in year two after implantation. This coincided with a statistically significant decrease in infections over the same time period in treated children.

In total 29 patients enrolled in the studies died, 23 in the first year after treatment. Six died after one year, but these were from causes not considered to be linked to treatment with Rethymic such as cardiopulmonary arrest and intracranial hemorrhage.

In addition to the need for caution and monitoring for infections while the implant takes effect, as with other similar immune therapies, there is a risk that patients given the implant will develop graft versus host disease and puts them at higher risk for a range of other immune system related conditions.

Enzyvant suffered a setback in 2019 when Rethymic was rejected by the FDA because of questions around the chemistry, manufacturing and controls (CMC) processes used to manufacture the therapy.

However, it addressed all the issues raised and resubmitted to the FDA earlier this year with last weeks announcement finally allowing the biotech to offer this potentially life-saving therapy to more children.

“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, principal investigator on the 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.”

Pricing for Rethymic as well as information about its availability in the U.S., as well as other countries, has yet to be announced by the company.

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