Prior to 2021, there were no FDA-approved treatments for patients with type 1 plasminogen deficiency, or hypoplasminogenemia. As a result, there was an urgent need to fill this unmet need within this patient population. However, things have now changed! On June 4, 2021, the FDA announced that it had approved Ryplazim (plasminogen, human-tvmh) for patients with hypoplasminogenemia.

Hypoplasminogenemia

Also known as type 1 plasminogen deficiency, hypoplasminogenemia is a rare genetic disorder characterized by low or deficient plasminogen levels. Overall, PLG gene mutations cause hypoplasminogenemia. Normally, PLG encodes for the production of plasminogen. Later, plasminogen activators turn plasminogen into plasmin, which helps dissolve fibrin clots. However, in patients with hypoplasminogenemia, the deficient or low levels of plasminogen prevent these clots from being dissolved. As a result, inflamed growths or legions form on mucous membranes. These lesions interrupt tissue growth and can impair organ function. Most commonly, these growths affect the conjunctiva of the eye and may frequently recur, even after removal. Without treatment, conjunctival hypoplasminogenemia can cause vision loss or blindness. Symptoms often appear in infancy. These symptoms include:

• Gingivitis
• Corneal tears or scarring
• Ligneous conjunctivitis
  • Note: This form of conjunctivitis causes inflammation around the eyelids. Additionally, ligneous conjunctivitis manifests in the development of yellow, white, or red thick and woody growths.
• The formation of ligneous growths in the vagina, mouth, or nasal cavities
• Gastrointestinal ulcers
• Obstructed airways and difficulty breathing
• Kidney inflammation and/or kidney stones
• Hydrocephalus (excess fluid in the skull)
• Hearing and vision abnormalities
• Cervicitis

Learn more about hypoplasminogenemia.

Ryplazim

The FDA’s approval was granted to ProMetic Biotherapeutics, Inc. (“ProMetic”), a subsidiary of Liminal BioSciences. According to a prior press release regarding Ryplazim development, Liminal BioSciences described Ryplazim as:

an investigational plasma-derived protein [that] acts as a replacement therapy for activated plasminogen, a fundamental component of the fibrinolytic system and the main enzyme involved in the lysis of blood clots, clearance of extravasated fibrin and other vital physical processes.

Since patients with hypoplasminogenemia lack plasminogen, Ryplazim works to replenish plasminogen levels. Through doing so, the drug allows the body to break down fibrin clots and accumulation, reducing related health impacts. Researchers determined the safety, efficacy, and tolerability of Ryplazim through a clinical trial in which 15 patients enrolled. During the trial, patients received Ryplazim every 2-4 days for a total of 48 weeks (approximately 11 months). Ultimately, researchers determined that:

• During the trial, patients did not develop any new lesions or see any recurring lesions.
• All patients who began the trial with hypoplasminogenemia-related lesions saw at least a 50% improvement rate.
• Altogether, Ryplazim was relatively safe and well-tolerated. Side effects included:
  • Dry mouth
  • Constipation
  • Abdominal, limb, back, and joint pain
  • Fatigue
  • Nausea
  • Bloating
  • Dizziness
  • Bleeding or shedding from active lesions

Prior to its approval, Ryplazim received Orphan Drug, Fast Track, Rare Pediatric Disease, and Priority Review designations. Now, the therapy can be used to improve the lives of patients with hypoplasminogenemia.