Announcement • 8h
Ultragenyx Pharmaceutical Inc Announces FDA Approval Of GENGLYCOS Gene Therapy For Glycogen Storage Disease Type Ia
Ultragenyx Pharmaceutical Inc. announced that the U.S. Food and Drug Administration granted accelerated approval for GENGLYCOS (pariglasgene brecaparvovec-opnr), also known as DTX401, in adult and pediatric patients eight years and older with glycogen storage disease type Ia (GSDIa). GENGLYCOS is the first gene therapy approval, and fifth FDA approval overall, for the company. Approval provides a long-awaited first-ever option to reduce the burden of care associated with GSDIa. Ultragenyx received a Priority Review Voucher upon approval. GENGLYCOS fulfills the commitment to provide the first therapy that directly targets the root cause of GSDIa. The reduced reliance on cornstarch, experienced by patients in clinical studies, demonstrates this gene therapy’s ability to establish the normal breakdown of glycogen to produce glucose during fasting or episodes of metabolic stress. This ability to regulate glucose has alleviated the disease burden and has the potential to mitigate the risk of severe or life-threatening hypoglycemia for these patients. GSDIa is an ultra-rare genetic metabolic disorder caused by a deficiency of the enzyme needed to release glucose from the liver to the bloodstream. The deficiency reduces the liver’s ability to control glucose levels and is associated with potentially life-threatening hypoglycemia episodes and other serious complications, requiring rigorous nutritional management that involves a burdensome, around-the-clock regimen of raw cornstarch intake as an oral glucose replacement therapy. Glucose control with cornstarch is crude with large swings in glucose, and patients instead end up spending a large fraction of their day significantly hyperglycemic to avoid hypoglycemic episodes. GSDIa affects 1,500-2,500 patients in the U.S. and 6,000-8,000 worldwide within commercially accessible geographies. Clinical Program and Post-Marketing Study Requirements Supporting Accelerated Approval of GENGLYCOS: The approval of GENGLYCOS is based on positive data from the 48-week randomized, double-blind, placebo-controlled Phase 3 GlucoGene study which treated 46 participants aged eight years and older with DTX401 (1.0 x 10^13 GC/kg dose) or placebo, showing a reduction in the cornstarch requirements in the treated group. GENGLYCOS will be available through a national network of Qualified Treatment Centers (QTCs) with specialized expertise and training to safely administer gene therapy. GENGLYCOS is manufactured entirely at Ultragenyx’s Gene Therapy Manufacturing Facility (GTMF) in Bedford, Mass., strengthening the Company’s ability to scale production of high-quality gene therapy products and deliver them to patients as efficiently as possible. GENGLYCOS (pariglasgene brecaparvovec-opnr) is indicated to reduce daily cornstarch intake as an adjunct to nutritional management in adult and pediatric patients 8 years of age and older with glycogen storage disease type Ia (GSDIa). This indication is approved under accelerated approval based on reduction in daily cornstarch intake. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s). GENGLYCOS is contraindicated in patients with known severe hepatic fibrosis or cirrhosis. Hypersensitivity reactions including anaphylaxis and infusion reactions have occurred with GENGLYCOS treatment. Severe reactions have been reported. Monitor for signs and symptoms of hypersensitivity and infusion reactions, including urticaria, flushing, hypotension, bronchospasm, dyspnea, chest tightness, nausea, vomiting, headache, abdominal pain, lightheadedness, flu-like symptoms, shivering, rash, and hypertension. Premedicate with acetaminophen and non-sedating antihistamines and administer GENGLYCOS according to recommended infusion rates. Monitor patients during and after completion of GENGLYCOS infusion as clinically indicated. If anaphylaxis or severe infusion reaction occurs, pause GENGLYCOS infusion immediately and initiate medical treatment as clinically indicated, monitoring as needed. For mild to moderate infusion reactions, consider slowing or temporarily interrupting the infusion, and administer symptomatic treatment as clinically indicated. The infusion may be restarted at half the prior rate upon resolution of symptoms. Medical support measures, including cardiopulmonary resuscitation equipment and medications for the treatment of anaphylaxis (e.g., epinephrine, antihistamines, corticosteroids), should be available during GENGLYCOS administration. Immune-mediated hepatotoxicity, with elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels, has occurred with GENGLYCOS. Avoid use in patients with preexisting hepatic impairment or acute hepatic viral infection. Prior to GENGLYCOS infusion, evaluate liver-related medical history and assess liver function by clinical examination and laboratory testing. Advise patients to immediately report signs and symptoms of hepatotoxicity, including fatigue, jaundice, dark urine, nausea, vomiting, and right upper quadrant pain. Administer corticosteroids to all patients after GENGLYCOS infusion in order to mitigate hepatic reactions. Elevated transaminases may require adjustment of the corticosteroid treatment regimen, including increased dose or prolongation of the corticosteroid taper. Monitor transaminase levels for the first 6 months after GENGLYCOS administration. Continue to monitor transaminases in all patients who develop transaminase elevations, until transaminases return to baseline or as clinically indicated. Adrenal insufficiency, including serious events, has been reported in patients receiving GENGLYCOS during corticosteroid use and tapering. Signs and symptoms of adrenal insufficiency include fatigue, weakness, anorexia, nausea, vomiting, hypotension, hyponatremia, and hypoglycemia. Adrenal crisis may present as severe hypotension, acute abdominal pain, or loss of consciousness. Monitor patients for signs and symptoms of adrenal insufficiency and adrenal crisis after GENGLYCOS administration during and after corticosteroid therapy and tapering. Taper corticosteroid therapy gradually. Do not abruptly discontinue corticosteroid therapy. There is a theoretical risk of tumorigenicity due to integration of AAV vector DNA into the genome. GENGLYCOS is composed of a recombinant, non-replicating AAV8 vector whose DNA persists largely in episomal form. Random integration of recombinant AAV-vector DNA into human DNA has been reported with AAV gene therapies.
