Enzyvant receives FDA approval for its treatment for congenital athymia
Ultra-Orphan Pipeline: Life-saving treatment for congenital athymiaOctober 15, 2021
Disease State Background:1-4 Congenital athymia is an ultra-rare disease where the patient is born with a complete lack of a functional thymus, leading to severe immunodeficiency due to inability to produce normally functioning T-cells. Without immune system reconstitution, children cannot fight infections and typically die within the first 24 months of life. According to Enzyvant, approximately 20 infants a year are born with congenital athymia in the United States.
RVT-802:1-5 Thymus tissue is obtained from infants <9 months of age with congenital heart disease during open heart surgery (the thymus is located on top of the heart at birth). The removed thymus tissue is cut into thin slices (0.5 mm) and cultured for 12-21 days which depletes the donor thymocytes. The tissue is evaluated for microbiological contamination and histological features. HLA matching is not required for most patients as they do not have a functioning immune system. The tissue is implanted into the quadriceps muscle of the infant recipient where bone marrow stem cells migrate to and eventually become naïve, immunocompetent T cells. The procedure takes approximately 1.5 hours and will only be performed at Duke University Medical Center.
Efficacy:2,5 As of the BLA filing in June 2019, a total of 85 patients who received RVT-802 met criteria for inclusion for the efficacy analysis. Naïve T-cell emergence typically occurs at six months after implantation. The Kaplan-Meier estimate of survival at year one was 76% (95% CI: 66-84%), and year two post treatment was 75% (95% CI: 63-83%), respectively. For patients surviving 12 months post-treatment, there is a 93% probability of surviving 10 years post-treatment.
- Survival was maintained: The longest surviving patient has been followed for almost 24 years as of August 2019.
- Safety:2,5 The most commonly reported RVT-802 adverse events: thrombocytopenia (11%), neutropenia (8%), pyrexia (5%), and proteinuria (5%).
Other Treatment Options:1-5 There are no FDA-approved treatment options. Treatments that have been tried in the past with various success include: T-cell replete hematopoietic stem cell transplantation and total thymus transplantation. The only U.S. medical center that performs thymus transplants is Duke Children’s Hospital with an overall survival rate of 71%.
Anticipated cost: Prime expects few utilizers, but anticipates RVT-802 will be high cost. Enzyvant has noted that the price will be similar to other one-time treatments. For comparison, the wholesale acquisition cost (WAC) of chimeric antigen receptor T-cell (CAR-T) therapy is $373,000. But real-world costs average more than $700,000, and in some cases exceed $1 million, according to data from a recent Prime study.6
1. Enzyvant.com Area of focus. Accessed in August 2021 at: https://enzyvant.com/areas-of-focus/
a. Biospace.com Enzybant resubmits biologics licensing application (BLA) to FDA for RVT-802 for pediatric congenital athymia. Accessed in August 2021 at: https://www.biospace.com/article/releases/enzyvant-resubmits-biologics-licensing-application-bla-to-fda-for-rvt-802-for-pediatric-congenital-athymia/
2. Data on File. Enzyvant.
3. Markert ML, Devlin BH, McCarthy EA. Thymus transplantation. Clin Immuno 2010; 135(2): 236-246.
4. Janda A, Sedlacek P, Honig M, et al. Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly. Blood 2010; 116(13): 2229-2236.
5. Duke.edu Enzyvant announces FDA acceptance of biologics license application (BLA) and priority review status for RVT-802, a novel investigational tissue-based regenerative therapy for pediatric congenital athymia. Accessed in November at: https://olv.duke.edu/news/enzyvant-announces-fda-acceptance-of-biologics-license-application/
6. Primetherapeutics.com Prime Therapeutics’ study shows total cost of care for CAR-T plus post-treatment events can exceed $1 million. Accessed in August 2021 at: https://www.primetherapeutics.com/en/news/pressreleases/2021/release-2021-cost-of-care-car-t-exceed-million.html
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