Congenital plasminogen deficiency is caused by mutations in PLG, the gene coding for production of the
zymogen plasminogen, and is an ultrarare disorder associated with abnormal accumulation or growth of
fibrin-rich pseudomembranous lesions on mucous membranes. Left untreated, these lesions may impair organ function and impact quality of life.
Plasminogen replacement
therapy should provide an effective treatment of the manifestations of
congenital plasminogen deficiency. An open-label phase 2/3 study of human
Glu-plasminogen administered IV at 6.6 mg/kg every 2 to 4 days in 15 patients with
congenital plasminogen deficiency is ongoing. Reported here are data on 14 patients who completed at least 12 weeks of treatment. The primary end point was an increase in trough
plasminogen activity levels by at least an absolute 10% above baseline. The secondary end point was clinical success, defined as ≥50% improvement in lesion number/size or functionality impact from baseline. All patients achieved at least an absolute 10% increase in trough
plasminogen activity above baseline. Clinical success was observed in all patients with clinically visible (conjunctiva and gingiva), nonvisible (nasopharynx, bronchus, colon, kidney, cervix, and vagina), and wound-healing manifestations of the disease.
Therapeutic effects were rapid, as all but 2 lesions resolved or improved after 4 weeks of treatment. Human
Glu-plasminogen was well tolerated in both children and adults. This study provides critical first evidence of the clinical utility of ongoing replacement
therapy with human
Glu-plasminogen for the treatment of children and adults with
congenital plasminogen deficiency. This trial was registered at www.clinicaltrials.gov as #NCT02690714.