One particular kind of SCID, called adenosine deaminase deficiency (ADA)-SCID, is caused by lack of an enzyme (a protein in the body that helps break down other chemicals). Patients with ADA-SCID typically have very low T-cells, B-cells, and NK-cells because toxic byproducts build up as result of lack of the ADA enzyme. Patients with ADA-SCID present with similar infections as seen with the other forms of SCID.
ADA-SCID is the only type of SCID where patients can receive enzyme replacement. The enzyme has been made into a drug known as SC-PEG-rADA (elapegademase; Revcovi ®). SC-PEG-rADA is a recombinant form of the bovine ADA that does not come from animals and replaces the formerly available bovine PEG-ADA (Adagen ®). SC-PEG-rADA is given by a needle into the muscle (intramuscularly). Patients / parents learn to inject it themselves. Usually it is given once per week, although dose changes (both in terms of total dose and the frequency with which SC-PEG-rADA is administered) may need to occur based upon ADA levels that are monitored in the blood.
Patients with ADA-SCID can take SC-PEG-rADA for their entire lifetime. In some situations it is used as a “bridge” to transplant (i.e. used to improve the immune system temporarily while a patient is awaiting more definitive therapy). It is controversial which approach is better. One of the goals of the PIDTC 6901 and 6902 studies is to understand long-term outcomes for both SC-PEG-rADA and transplant for ADA-SCID.
Company-sponsored clinical trials assessing whether patients develop antibodies recognizing SC-PEG-rADA have found that patients who previously received PEG-ADA (Adagen) may present a transient immunologic response to SC-PEG-rADA. Since PEG-ADA is the same class of ERT used in the treatment of ADA-SCID, the following adverse reactions may also be seen with SC-PEG-rADA treatment: hemolytic anemia, auto-immune hemolytic anemia, thrombocythemia, thrombocytopenia, injection site erythema/urticaria, and lymphomas.