Safety and Efficacy of Long-Term Treatment of Type 1 Plasminogen Deficient Patients With Intravenous Plasminogen Replacement Therapy.

Introduction: Type 1 plasminogen deficiency (PLGD-1), or hypoplasminogenaemia, is an ultra-rare autosomal-recessive disorder characterised by fibrin-rich lesions on mucous membranes, often leading to serious complications if left untreated. Prior treatments have shown limited and inconsistent success, but IV PLG concentrate (Ryplazim) offers a targeted therapy.

Aim: This study investigated the long-term safety and efficacy of IV PLG concentrate treatment for PLGD-1 patients.

Methods: A long-term study (NCT03642691) followed 12 participants who had previously been included in pivotal or expanded access trials of IV PLG concentrate. Participants received 6.6 mg/kg IV PLG concentrate infusions, with dosing frequency adjusted based on clinical response and plasminogen levels. Safety assessments and plasminogen level measurements were conducted.

Results: The median treatment duration during this long-term follow-up study was 41 months (range: 25-42 months). The median total exposure for participants in this study throughout the clinical development was 68 months (range: 28-71 months). No new or recurring ligneous lesions occurred when participants adhered to the prescribed regimen. Temporary disruptions in the drug supply led to some lesion recurrences, which resolved upon resuming the prescribed dosing frequency. A total of 2165 infusions were administered in this study, and most adverse events were mild. No anti-plasminogen antibodies or treatment-related fatalities occurred.

Conclusion: Long-term treatment with IV PLG concentrate is safe and effective for PLGD-1, demonstrating the potential for tailored dosing regimens. This study highlights the importance of individualised treatment and provides valuable insights into managing this ultra-rare disorder.