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

Abstract

IntroductionType 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.AimThis study investigated the long‐term safety and efficacy of IV PLG concentrate treatment for PLGD‐1 patients.MethodsA 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.ResultsThe 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.ConclusionLong‐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.

Bilateral infection-triggered ligneous conjunctivitis in a 6-month-old patient treated successfully with heparin and allogenic serum eye drops

“… 5 Past treatment strategies have included systemic treatments with FFP or IV administration of plasminogen, human-tvmh (Ryplazim, Prometic Biotherapeutics Inc., Laval, Canada), a plasma-derived human Glu-PLG. 4 , 5 These treatments are limited by the risk of systemic complications, as well as the high burden associated with the need for frequent IV administrations. 4 , 6 Their use is, therefore, commonly restricted to patients requiring systemic therapy for disease with multiorgan involvement.…”

“… 4 , 5 These treatments are limited by the risk of systemic complications, as well as the high burden associated with the need for frequent IV administrations. 4 , 6 Their use is, therefore, commonly restricted to patients requiring systemic therapy for disease with multiorgan involvement.…”

“… 1 , 3 Treatment approaches to systemic disease include administration of fresh frozen plasma (FFP) or intravenous (IV) plasminogen; however, both carry non-negligible risks for adverse events such as nasopharyngitis, oropharyngeal pain and headaches. 4 For patients with clinically isolated LC, reported topical treatment options include topical plasminogen drops, cyclosporin A, corticosteroids or surgical excision; however, these treatment options show inconsistent success and currently there are no established guidelines for the treatment of LC nor PLGD. 2 Due to the ultra-rare nature of the disease, large prospective clinical trials and cohort studies are difficult to implement.…”

Bilateral infection-triggered ligneous conjunctivitis in a 6-month-old patient treated successfully with heparin and allogenic serum eye drops

“… 5 Past treatment strategies have included systemic treatments with FFP or IV administration of plasminogen, human-tvmh (Ryplazim, Prometic Biotherapeutics Inc., Laval, Canada), a plasma-derived human Glu-PLG. 4 , 5 These treatments are limited by the risk of systemic complications, as well as the high burden associated with the need for frequent IV administrations. 4 , 6 Their use is, therefore, commonly restricted to patients requiring systemic therapy for disease with multiorgan involvement.…”

“… 4 , 5 These treatments are limited by the risk of systemic complications, as well as the high burden associated with the need for frequent IV administrations. 4 , 6 Their use is, therefore, commonly restricted to patients requiring systemic therapy for disease with multiorgan involvement.…”

“… 1 , 3 Treatment approaches to systemic disease include administration of fresh frozen plasma (FFP) or intravenous (IV) plasminogen; however, both carry non-negligible risks for adverse events such as nasopharyngitis, oropharyngeal pain and headaches. 4 For patients with clinically isolated LC, reported topical treatment options include topical plasminogen drops, cyclosporin A, corticosteroids or surgical excision; however, these treatment options show inconsistent success and currently there are no established guidelines for the treatment of LC nor PLGD. 2 Due to the ultra-rare nature of the disease, large prospective clinical trials and cohort studies are difficult to implement.…”

Sustained Therapeutic Efficacy of Intravenous Plasminogen Concentrate in Pediatric Patients With Type 1 Plasminogen Deficiency: An Analysis of Dosing Parameters and Clinical Outcomes

“…Patients enrolled in the pivotal trial, except for Patient 1, enrolled in the long-term study after the end-of-study visit. The study design, inclusion and exclusion criteria, and endpoints have been previously described for the pivotal and long-term studies [36][37][38].…”

Bilateral infection-triggered ligneous conjunctivitis in a 6-month-old patient treated successfully with heparin and allogenic serum eye drops

“… 5 Past treatment strategies have included systemic treatments with FFP or IV administration of plasminogen, human-tvmh (Ryplazim, Prometic Biotherapeutics Inc., Laval, Canada), a plasma-derived human Glu-PLG. 4 , 5 These treatments are limited by the risk of systemic complications, as well as the high burden associated with the need for frequent IV administrations. 4 , 6 Their use is, therefore, commonly restricted to patients requiring systemic therapy for disease with multiorgan involvement.…”

“… 4 , 5 These treatments are limited by the risk of systemic complications, as well as the high burden associated with the need for frequent IV administrations. 4 , 6 Their use is, therefore, commonly restricted to patients requiring systemic therapy for disease with multiorgan involvement.…”

“… 1 , 3 Treatment approaches to systemic disease include administration of fresh frozen plasma (FFP) or intravenous (IV) plasminogen; however, both carry non-negligible risks for adverse events such as nasopharyngitis, oropharyngeal pain and headaches. 4 For patients with clinically isolated LC, reported topical treatment options include topical plasminogen drops, cyclosporin A, corticosteroids or surgical excision; however, these treatment options show inconsistent success and currently there are no established guidelines for the treatment of LC nor PLGD. 2 Due to the ultra-rare nature of the disease, large prospective clinical trials and cohort studies are difficult to implement.…”

Sustained Therapeutic Efficacy of Intravenous Plasminogen Concentrate in Pediatric Patients With Type 1 Plasminogen Deficiency: An Analysis of Dosing Parameters and Clinical Outcomes

“…Patients enrolled in the pivotal trial, except for Patient 1, enrolled in the long-term study after the end-of-study visit. The study design, inclusion and exclusion criteria, and endpoints have been previously described for the pivotal and long-term studies [36][37][38].…”

Bilateral infection-triggered ligneous conjunctivitis in a 6-month-old patient treated successfully with heparin and allogenic serum eye drops

“… 5 Past treatment strategies have included systemic treatments with FFP or IV administration of plasminogen, human-tvmh (Ryplazim, Prometic Biotherapeutics Inc., Laval, Canada), a plasma-derived human Glu-PLG. 4 , 5 These treatments are limited by the risk of systemic complications, as well as the high burden associated with the need for frequent IV administrations. 4 , 6 Their use is, therefore, commonly restricted to patients requiring systemic therapy for disease with multiorgan involvement.…”

“… 4 , 5 These treatments are limited by the risk of systemic complications, as well as the high burden associated with the need for frequent IV administrations. 4 , 6 Their use is, therefore, commonly restricted to patients requiring systemic therapy for disease with multiorgan involvement.…”

“… 1 , 3 Treatment approaches to systemic disease include administration of fresh frozen plasma (FFP) or intravenous (IV) plasminogen; however, both carry non-negligible risks for adverse events such as nasopharyngitis, oropharyngeal pain and headaches. 4 For patients with clinically isolated LC, reported topical treatment options include topical plasminogen drops, cyclosporin A, corticosteroids or surgical excision; however, these treatment options show inconsistent success and currently there are no established guidelines for the treatment of LC nor PLGD. 2 Due to the ultra-rare nature of the disease, large prospective clinical trials and cohort studies are difficult to implement.…”

Sustained Therapeutic Efficacy of Intravenous Plasminogen Concentrate in Pediatric Patients With Type 1 Plasminogen Deficiency: An Analysis of Dosing Parameters and Clinical Outcomes

“…Patients enrolled in the pivotal trial, except for Patient 1, enrolled in the long-term study after the end-of-study visit. The study design, inclusion and exclusion criteria, and endpoints have been previously described for the pivotal and long-term studies [36][37][38].…”