New long-term clinical data from the Phase 2/3 trial of Ryplazym (plasminogen IV), indicates that it can prevent lesions from recurring in patients with congenital plasminogen deficiency, according to the drug’s maker Prometic Life Sciences.
“This pivotal Phase 2/3 trial of Ryplazym has successfully met all primary and secondary endpoints, and we are pleased to announce these follow-up results which confirm the durability of the positive clinical efficacy and safety profile out to 48 weeks”, a press release from Prometic quoted Dr. John Moran, chief medical officer of the company, as saying.”The 48-week clinical data will be submitted as a supplement to our BLA filing after RyplazymTM receives its expected accelerated approval in the fourth quarter of 2017.”
The most common condition 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 lesion of plasminogen deficiency, hypoplasminogen mia is a multi-systemic disease that can also affect the ears, sinuses, tracheobronchial tree, genitourinary tract, and gingiva.
Tracheobronchial lesions including hyperviscous secretions can result in respiratory failure. Hydrocephalus has also been reported in children with severe hypoplasminogenmia, thought to be related to the deposition of fibrin in the cerebral ventricles.
Plasminogen is a naturally occurring protein that is synthesized by the liver and circulates in the blood.
Activated plasminogen, plasmin, is a fundamental component of the fibrinolytic system and is the main enzyme involved in the lysis of blood clots and clearance of extravasated fibrin.
Plasminogen is vital in wound healing, cell migration, tissue remodeling, angiogenesis, and embryogenesis.
Prometic has previously reported data from this Phase 2/3 trial, which showed that Ryplazym treatment consistently replaced and maintained the plasminogen concentration at an appropriate level and that it resolved all lesions in all 10 patients treated for 12 weeks.
The findings fulfilled the clinical information required for the Biologics License Application (BLA) filing with the US Food and Drug Administration (FDA) for the Accelerated Regulatory Pathway Approval.
Under the same Phase 2/3 protocol, the 10 patients were treated for an additional 36 weeks, for a total drug exposure period of 48 weeks. In addition to the dossier filed with the FDA, the 48-week clinical efficacy data will form the basis for the upcoming regulatory filing with Health Canada in the fourth quarter of 2017.
The Ryplazym Phase 2/3 trial is still underway.
The dataset for all 15 patients that will have been treated over a period of 48 weeks is expected to be an acceptable demonstration of the efficacy of plasminogen therapy in patients with plasminogen congenital deficiency for full licensure, without the need for any additional clinical trials, according to Prometic.