Pharmacy Prior Authorization Criteria

Ryplazim (plasminogen, human-tvmh)

Indications for Prior Authorization

Ryplazim (plasminogen, human-tvmh)

• For diagnosis of Hypoplasminogenemia
  Indicated for the treatment of patients with plasminogen deficiency type 1 (hypoplasminogenemia).

Criteria

Ryplazim

Prior Authorization (Initial Authorization)

Length of Approval: 6 Month(s)

• Diagnosis of plasminogen deficiency type 1 (hypoplasminogenemia) as confirmed by both of the following [2, A, B]:
• Deficiency of plasminogen activity evidenced by a level of less than or equal to 50%, as confirmed by a chromogenic assay [3-5, B]
AND
• Abnormal plasminogen antigen plasma level of less than 9 mg/dL, as confirmed by an enzyme-linked immunosorbent assay [3-5, B]
AND
• Presence of clinical symptoms and signs of the disease (e.g., ligneous conjunctivitis, ligneous gingivitis, occlusive hydrocephalus) [1, 5, A]
AND
• Prescribed by or in consultation with a hematologist

Ryplazim

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)

• Patient demonstrates positive clinical response to therapy (e.g., plasminogen activity trough level increased by at least 10 percentage points from baseline, improvement or resolution of lesions) [5, C]

P & T Revisions

2024-10-16, 2023-10-31, 2022-11-18, 2021-12-06

References

1. Mehta R and Shapiro AD. Plasminogen deficiency. Haemophilia. 2008; 14:1261-1268. doi: 10.1111/j.1365-2516.2008.01825.x
2. Ryplazim Prescribing Information. Prometic Biotherapeutics, Inc. Fort Lee, New Jersey. January 2024
3. Schuster V, Hügle B, Tefs K. Plasminogen deficiency. J Thromb Haemost. 2007;5(12):2315-2322. doi:10.1111/j.1538-7836.2007.02776.x
4. Schuster V, Seregard S. Ligneous conjunctivitis. Surv Ophthalmol. 2003;48(4):369-388. doi:10.1016/s0039-6257(03)00056-0
5. Shapiro AD, Nakar C, Parker JM, et al. Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency. Blood. 2018;131(12):1301-1310. doi:10.1182/blood-2017-09-806729

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End Notes

1. The diagnosis of pseudo-membranous disease secondary to plasminogen deficiency requires both clinical and laboratory findings. Clinical symptoms from ligneous lesions and abnormally decreased plasminogen activity establishes the diagnosis [1].
2. Laboratory evaluation for plasminogen deficiency should include both plasminogen antigen and activity level. The study procedures in the Shapiro et al clinical trial included measuring plasminogen activity using a commercially available chromogenic assay and measuring plasminogen antigen using a commercially available enzyme-linked immunosorbent assay. Decreased plasminogen activity and concordant decrease in protein level is associated with plasminogen deficiency type 1, whereas patients with plasminogen deficiency type II have reduced plasminogen activity but normal or only slightly reduced plasminogen antigen level and have never been reported to develop pseudo-membranous lesions at other mucosal sites. Plasminogen values in patients with hypoplasminogenemia ranged from < 1 to 9 mg/dL for plasminogen antigen plasma level and < 1%-51% for functional plasminogen activity. These values provide a rough threshold between symptomatic and asymptomatic hypoplasminogenemia [3-5].
3. The primary end point success of the clinical study was defined as at least 80% of evaluable patients achieving target trough plasminogen activity levels, which was an increase of individual plasminogen activity trough level by at least an absolute 10% above baseline for at least 3 measurements in 12 weeks. The secondary end point success was defined as 50% of patients with clinically visible or other measurable lesions achieving ≥ 50% reduction in lesion number and/or size or improved organ function [5].

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Revision History

• 2024-10-16: 2024 UM Annual review. No criteria changes. Background updates
• 2023-10-31: 2023 UM Annual Review. Updated reauth language to standard "patient demonstrates" and updated references
• 2022-11-18: Annual review - updated references.
• 2021-12-06: New Program

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