The US Food and Drug Administration (FDA) has approved elapegademase-lvlr (Revcovi, Leadiant Biosciences) for the treatment of adults and children with adenosine deaminase severe combined immune deficiency (ADA-SCID) — an "ultra-rare, inherited genetic disorder" in which the adenosine deaminase (ADA) enzyme is deficient, according to a company news release
ADA-SCID compromises the immune system, leaving patients vulnerable to infectious bacteria, viruses, and fungi; it is fatal if untreated.
"For decades, physicians, patients, and their families have relied upon enzyme replacement therapy as a life-saving treatment for adenosine deaminase severe combined immunodeficiency, a disease in which the buildup of toxic metabolites can cripple children's immune systems," Morna Dorsey, MD, MMSc, professor of pediatrics at the University of California, San Francisco, said in the news release. "Individuals with ADA-SCID are at an increased risk of severe and recurrent infections and often fail to thrive. By providing specific and direct replacement of the adenosine deaminase enzyme, Revcovi can reduce patients' risk of potentially serious, life-threatening infections and their debilitating complications."
Elapegademase-lvlr is a new injectable PEGylated recombinant adenosine deaminase (rADA) enzyme that supplements ADA levels and does not need to be sourced from animals. The FDA designated elapegademase-lvlr as an orphan drug and gave Fast Track and Priority Review status to the application.
The approval follows consideration of data from two multicenter, open-label clinical trials that showed elapegademase-lvlr increased ADA activity, decreased concentrations of toxic metabolites usually seen in patients with ADA-SCID, and improved total lymphocyte counts.
The company is conducting a postmarketing clinical study that will collect information about the health status of patients using the drug and provide additional safety and efficacy data, particularly in patients who have been newly diagnosed with the disorder.
Patients with thrombocytopenia may experience injection site bleeding; therefore, elapegademase-lvlr is contraindicated in those with severe thrombocytopenia. Immune-deficient patients should be protected from infections until their immune function improves.
The most frequent adverse effects were cough and vomiting. Postmarketing reports of adverse events in patients taking the same class of enzyme replacement therapy include hematologic events, such as hemolytic anemia, autoimmune hemolytic anemia, thrombocythemia, thrombocytopenia, and autoimmune thrombocytopenia; dermatological events, including injection site erythema and urticaria; and lymphomas. These may also occur in patients taking elapegademase-lvlr.
Trough plasma ADA activity and trough dAXP (total 2'-deoxyadenosine nucleotides) levels should be monitored in patients undergoing treatment with elapegademase-lvlr to maintain therapeutic targets. In patients with persistently low plasma ADA activity, monitor immune function and clinical status and take precautions to minimize the risk for infection.
Newborns in most states are screened for ADA-SCID at birth, and it is usually diagnosed within the first several months of life. As a result, ADA enzyme therapy is usually begun early, improving outcomes.
Between 1 in 200,000 and 1 in 1,000,000 newborns globally are estimated to have the disorder, which accounts for approximately 15% of SCID cases.
Patients with ADA-SCID experience severe, recurrent opportunistic infections, failure to thrive, extreme lymphopenia with nonexistent or profoundly impaired immune function, and metabolic abnormalities (such as an abnormally elevated intracellular buildup of purine nucleotides). When undiagnosed, children usually die of infections before age 2 years.
"We are gratified by the FDA's timely recognition of Revcovi as an effective and safe treatment for ADA-SCID, which, in addition to being ultra-rare, is one of the most devastating genetic disorders," Michael Minarich, chief executive officer, Leadiant Biosciences Inc, said in the news release.
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Cite this: FDA Approves Revcovi for Adenosine Deaminase SCID - Medscape - Oct 08, 2018.