What is Plasminogen Deficiency?
In all patients with plasminogen deficiency, plasma plasminogen levels are markedly reduced.1 Plasminogen is a naturally occurring protein that is synthesized by the liver and circulates in the blood. Activated plasminogen, known as plasmin, is an enzymatic component of the fibrinolytic system and the main enzyme involved in the lysis of clots and clearance of extravasated fibrin.2 Activated plasminogen is also involved in wound healing, cell migration, tissue remodeling, angiogenesis, and embryogenesis.3
Patients may be born with the inability to produce sufficient plasminogen naturally, a condition referred to as congenital plasminogen deficiency (C-PLGD). The most common and visible lesion associated with plasminogen deficiency is ligneous conjunctivitis, which is characterized by thick, woody (ligneous) growths on the conjunctiva of the eye, and if left untreated, can lead to corneal damage and blindness. Ligneous growths tend to recur after surgical excision, thereby requiring multiple surgeries.
While ligneous conjunctivitis is the best characterized and visible lesion, congenital plasminogen deficiency is a multi-systemic disease that can also affect the ears, sinuses, tracheobronchial tree, genitourinary tract, and gingiva. Tracheobronchial lesions including hyper viscous secretions can result in respiratory failure. Hydrocephalus, a condition related to the deposition of fibrin in the cerebral ventricular system, has also been reported in children with severe plasminogen deficiency.
The effectiveness and safety of Ryplazim® (plasminogen) is primarily based on one single-arm, open-label (unblinded) clinical trial enrolling 15 adult and pediatric patients with plasminogen deficiency type 1. All patients received Ryplazim® administered every two to four days for 48 weeks. The effectiveness of Ryplazim® was demonstrated by at least 50% improvement of their lesions in all 11 patients who had lesions at baseline, and absence of recurrent or new lesions in any of the 15 patients through the 48 weeks of treatment.
The most common side effects reported by patients who received Ryplazim® were abdominal pain, bloating, nausea, bleeding, limb pain, fatigue, constipation, dry mouth, headache, dizziness, joint pain, and back pain.
Through its’ US subsidiary, Prometic Biotherapeutics Inc., the Company resubmitted a BLA in September 2020 with the FDA seeking approval to treat patients with hypoplasminogenemia. The FDA granted approval on the 4th June 2021, as the first approved treatment for plasminogen deficiency type 1.
Ryplazim® (plasminogen) has previously been granted Orphan Drug and Rare Pediatric Disease Designations by the FDA for the treatment of congenital plasminogen deficiency.
Selected Relevant Publications:
Shapiro, Amy D. et al. ‘Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency’ Blood. 2018 Mar 22;131(12) :1301-1310.
Shapiro, Amy D. et al. ‘An international registry of patients with plasminogen deficiency (HISTORY)’ Haematologica. 2020 Mar; 105(3):554-561.
For further information please visit Clinicaltrials.gov
*Ryplazim® (plasminogen) is an FDA approved drug, in the US, for plasminogen deficiency type 1. For important safety information please visit the FDA website by clicking here.
- Tefs K, Gueorguieva M, Klammt J, et al. Molecular and clinical spectrum of type I plasminogen deficiency: a series of 50 patients. Blood. 2006;108(9):3021-3026.
- Collen D, Ong EB, Johnson AJ. Human plasminogen in vitro and in vivo evidence for the biological integrity of NH2-terminal glutamic acid plasminogen. hromb Res. 1975;7(4):515-529.
- Castellino FJ, Ploplis VA. Structure and function of the plasminogen/plasmin system. Thromb Haemost. 2005;93(4):647-654.