Rare Disease Report

Replacement Therapy for Plasminogen Deficiency Extremely Effective

DECEMBER 10, 2017
Jim Radke, PhD
New long-term data exhibiting the safety and efficacy of Prometic’s plasminogen in patients with congenital plasminogen deficiency were presented at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition. The results displayed the therapy’s clear clinical benefit.

Plasminogen deficiency is a rare congenital disease in which patients lack a sufficient plasminogen to properly degrade plasma proteins. Signs and symptoms vary, but often include fibrinous lesions in various organs, most notably in the eyes.

Currently, there are no approved therapies for plasminogen deficiency, and treatment depends on the location of the fibrous lesions and the level of discomfort it provides to the patient. Surgery to remove the lesions is commonly performed, however, tends to trigger the development of more lesions, which ultimately lead to the need for further surgical procedures. With the surgical approach for this condition, an unmet need lies in the simple fact that plasminogen deficiency is the result of an inability to properly manage fibrin, and fibrin is a necessary part of the healing process following any surgery.

Prometic has developed an intravenous plasminogen replacement therapy to treat and prevent extravascular fibrinous lesions in patients with plasminogen deficiency.

In the open-label study, 15 patients with plasminogen deficiency received plasminogen (6.6 mg/kg) for 48 weeks. During the study, patients were dosed every 2, 3, or 4 days based upon a pharmacokinetic (PK) profile geared toward maintaining a trough plasminogen activity level that was at least 10% above baseline values. Extravascular ligneous lesions were assessed at weeks 0, 4, 8, 12, and every subsequent 12 weeks up to 48 weeks. Data from 10 patients were presented at the ASH meeting in Atlanta. Patient Demographics are shown in Table 1.

Table 1. Patient Demographics (n = 10)
  2-11 years
  12 -17 years
  >17 years
2
2
6
  Male
  Female
2
8
Body weight (range) 65.2 Kg
Mean baseline plasminogen activity 24% ± 10.6

At the start of the study, 6 of the 10 subjects had 15 visible lesions. By the 12th week, most of those lesions (14 of 15) had completely resolved, and after 48 weeks, all 15 lesions were gone. No new lesions or recurrences of previous lesions were observed throughout the study. The therapy was well-tolerated with no serious adverse events (AEs) or AEs resulting in discontinuation reported. Nasopharyngitis was the most frequently reported AE.

Table 2. Efficacy
Time Visible Lesions New Lesions
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
15
2
1
1
0
0
0
-
0
0
0
0
0
0

The authors concluded that plasminogen replacement therapy “represents a pivotal breakthrough in the treatment of this very rare coagulation deficiency and an important therapeutic advance for affected patients who have suffered under the burden of their disease due to lack of an available efficacious therapy.”

Reference
Nakar CT, Parker JM, Thakral N, et al. Pivotal Trial with Intravenous Plasminogen Replacement in Patients with Plasminogen Deficiency Demonstrates Long-Term Efficacy for Treatment and Prevention of Ligneous Lesions. Presented at the 59th ASH Annual Meeting & Exposition, December 9-12, 2017; Atlanta GA. Abstract 84. https://ash.confex.com/ash/2017/webprogram/Paper100480.html

Copyright © RareDR 2013-2018 Rare Disease Communications. All Rights Reserved.