Plasminogen deficiency is a rare condition in which the lack of plasminogen – a protein synthesized by the liver and involved in the degradation of plasma proteins – leads to a variety of problems, including conjunctivitis and gingivitis that can impede vision.
At present, the only treatment option is surgery. Lesions, however, tend to return and multiple surgeries, especially ones involving the eyes, can lead to permanent damage.
Prometic Life Sciences is developing a potential treatment for plasminogen deficiency, and Rare Disease Report
spoke with Pierre Laurin, the president and chief executive officer of the company, about Ryplazim.
Rare Disease Report: Can you describe plasminogen and plasminogen deficiency
Plasminogen is involved in many healing processes. It actually interacts with over 34 receptors in the body. A person who does not have enough plasminogen will develop complications, mainly fibrous material will tend to grow, most notably in the eyes, the nasal-pharynx area, the bronchial tree. It can affect the kidney and the brain as well. So a plasminogen deficiency patient can have numerous fibrous lesions that can be life threatening. Right now, the only option they have is surgery to have the fibrous lesions removed – which can involve an ophthalmologist if the lesions are in the eyes, a nephrologist if in the kidney, etc.
Unfortunately, the surgery itself actually becomes a trigger for more lesions. So these patients have to undergo multiple surgeries and while the surgeries themselves are necessary to remove the lesions, they are also the trigger for more surgeries in the future. It’s a vicious cycle.
RDR: What is the therapy Prometic is developing for plasminogen deficiency?
We developed a process to extract plasminogen and be able to provide plasminogen to those patients who need plasminogen to dissolve their lesions in order to prevent the need for surgery. And that is the product we hope to bring to the market.
Ryplazim, as it is called, is plasminogen replacement therapy. This is a native, endogenous protein that is extracted by an FDA-approved process from plasma and processed, using a proprietary process, to form a stable form of plasminogen that can be stored in a vial. The product can be used for an acute care situation when the lesions are causing life threatening situations. It can also be administered in a home infusion set up and as maintenance therapy to avoid the recurrence of those lesions.
RDR: Is Replazim being reviewed by the FDA?
We have filed a BLA (Biologics License Application) with the FDA and it is under review right now. We hope to hear soon on when we can expect to receive a target date for approval.
Currently, based on various assumptions, we should be in a position to have a commercial launch for this product in Q1 of 2018.
We are also preparing to file for approval in Canada and Mexico. For Europe, we may need to wait for the entire Phase 3 to be completed. The FDA was satisfied with evidence of clinical efficacy for the first 10 patients in that trial that competed 12 weeks of treatment.
RDR: What did the efficacy data show in those first 10 patients?
There was a 100% response in those 10 patients. It was a remarkable result. Patients walked into that trial with visible lesions or lesions documented by CAT Scan or X-ray. They saw their lesions get resolved, sometimes in hours or within a couple weeks.
The infusion of plasminogen does not restore the plasminogen to 100% but it does restore it to levels that provides enough to digest those lesions.
We announced recently that those 10 patients have now competed over 48 weeks of treatment and there were no recurrences of any lesions as well as no adverse events throughout the program. So this is really impressive.
RDR: How is Ryplazim administered?
It is an infusion that initially will be given by a health professional but after 2 or 3 infusions we know that patients or their caregivers can usually administer the product at home. There will be home infusion centers for those who prefer that approach.
The frequency of the administration will depend on the patient and their condition. For acute care to remove lesions, infusions every 3 or 4 days will be likely but once the lesions are out, the maintenance treatment needed to prevent lesions from coming back will vary from patient to patient—maybe every second or third week.
RDR: You recently received a pediatric rare disease designation for this drug.
Yes. Pediatric cases of plasminogen deficiency tend to be more severe and the lesions they experience can be life threatening. Also the complications associated with plasminogen deficiency tend to be more severe in pediatric patients (hydrocephalus, airway blockage, blindness).
The pediatric designation also gives us a chance to be eligible for a Priority Review Voucher. This Voucher we can use for a future drug in our pipeline and/or monetize the voucher. These vouchers have been sold anywhere from $70 million to over $300 million in the recent past. So we are really proud to have received this pediatric designation. The program by the FDA is a great incentive for companies to focus on pediatric indications that are often overlooked.
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