Liminal BioSciences Resubmits BLA for Ryplazim for Congenital Plasminogen Deficiency

Liminal BioSciences announced the Company, through its U.S. subsidiary Prometic Biotherapeutics Inc., has filed a resubmission of the Biologics License Application (BLA) for Ryplazim® (plasminogen) (Ryplazim®) with the U.S. Food and Drug Administration (FDA) for the treatment of congenital plasminogen deficiency (C-PLGD).

"The resubmission of this BLA represents a significant milestone for Liminal BioSciences and we believe it has meaningful potential for patients and families affected by congenital plasminogen deficiency," said Kenneth Galbraith, Chief Executive Officer of Liminal BioSciences. "We look forward to continuing to work with the FDA toward our goal of achieving regulatory approval and making Ryplazim® available to patients with this congenital rare disease in the United States."

"C-PLGD is a rare multisystem disorder that can have a profound effect on a patient's health and quality of life. With no approved treatment available, C-PLGD is an area of significant unmet need throughout the world," said Dr. Amy Shapiro, Chief Executive Officer and Co-medical Director at the Indiana Hemophilia & Thrombosis Center, Inc. and principal investigator in the pivotal clinical trial supporting the BLA resubmission.  

In a pivotal phase 2/3 clinical trial for the treatment of C-PLGD, the Company enrolled 15 patients with C-PLGD, including six pediatric patients, for 48 weeks of therapy with Ryplazim®. All of the patients treated with Ryplazim® achieved at least the targeted increase from baseline in their individual trough plasminogen activity levels through 12 weeks of therapy. In addition, all patients who had active visible lesions when enrolled in the trial had complete healing of their lesions within 48 weeks of initiating therapy. Adverse events reported in the clinical study were characterized as mild, with no patient deaths, serious adverse events or adverse events that caused study discontinuation reported.

"We are grateful to all of the stakeholders who have worked tirelessly to help us reach this milestone, including our dedicated teams in manufacturing, quality control and clinical research at Liminal BioSciences and the study investigators, patients and families who have supported this development program for Ryplazim®. We are committed to bringing patients potentially the first FDA-approved treatment option for C-PLGD that could make a positive difference in their lives," said Moira Daniels, Head of Regulatory Affairs and Quality Assurance for Liminal BioSciences.

In 2017 the Company received a Complete Response Letter (CRL) in response to a BLA submission for Ryplazim®. The Company believes that the resubmission addresses the deficiencies outlined in the CRL, which were related to certain manufacturing procedures. The Company further believes that the amended BLA represents a Class 2 resubmission that would provide for a Prescription Drug User Fee Act (PDUFA) date for FDA review and action within six months from the date of the resubmission. Pending confirmation from the FDA that the resubmission addresses the issues raised in the CRL, current published guidance from the FDA is that they will indicate the new action due date in writing to the Company within 14 days of receipt of the BLA resubmission. The FDA previously granted Orphan Drug and Rare Pediatric Disease Designations for Ryplazim® for the treatment of C-PLGD.

Under the FDA's rare pediatric disease designation and voucher programs, the FDA may grant a priority review voucher (PRV) to a sponsor who receives a product approval for a "rare pediatric disease," which is defined as a disease in which serious or life-threatening manifestations primarily affect fewer than 200,000 people in the U.S. Subject to FDA approval of Ryplazim® for the treatment of C-PLGD, the Company may be eligible to receive one priority review voucher, which then could be redeemed to receive priority review for a subsequent marketing application or sold or transferred to another company.

Plasminogen is a naturally occurring protein that is synthesized by the liver and circulates in the blood. Activated plasminogen, plasmin, is a fundamental component of the fibrinolytic system and is the main enzyme involved in the lysis of blood clots and clearance of extravasated fibrin. Plasminogen is therefore vital in wound healing, cell migration, tissue remodeling, angiogenesis and embryogenesis. Patients may be born with the inability to produce sufficient plasminogen naturally, a condition referred to as congenital plasminogen deficiency, or suffer an acute or acquired deficiency following a trauma or an illness. Patients with congenital plasminogen deficiency experience an accumulation of fibrin growths or lesions on mucosal surfaces throughout the body. Many cases are first diagnosed in the pediatric population and, if left untreated, can lead to organ-compromising disease manifestations. Peer-reviewed publications report that the condition may have a prevalence of 1.6 cases per million globally. Proprietary data sources and analyses involving the U.S. population suggest that the number of people potentially affected by plasminogen deficiency in the United States may be greater than these earlier epidemiological estimates. Congenital plasminogen deficiency requires lifelong therapy to avoid recurrence of lesions. There are currently no approved therapies for the treatment of congenital plasminogen deficiency.