BOSTON and LONDON, Sept. 18, 2023 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced the U.S. Food and Drug Administration (FDA) has accepted the filing of its Biologics License Application (BLA) for OTL-200 in metachromatic leukodystrophy (MLD) under Priority Review. The agency has set a Prescription Drug User Fee Act (PDUFA) goal date of March 18, 2024.
“Today is another significant step forward for patients and families in the U.S. impacted by this devastating and cruel disease who for too long have dealt with the unimaginable burden of going through the diagnostic odyssey, being told there were no treatments beyond supportive care, and then having to watch their child slip away,” said Bobby Gaspar, M.D., Ph.D., co-founder and chief executive officer of Orchard Therapeutics. “We look forward to collaborating with the FDA throughout the review and evaluation of our application. Due to the nature of the disease and the urgency to treat children affected by MLD, we are working diligently in parallel to prepare for a potential launch in 2024 and ensure OTL-200 will be available to patients in the U.S. as quickly as possible.”
About Metachromatic Leukodystrophy (MLD)
MLD is a rare and life-threatening inherited disease of the body’s metabolic system estimated to occur in approximately one in every 100,000 live births based on existing literature. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. In its late infantile form, mortality at five years from onset is estimated at 50 percent and 44 percent at 10 years for juvenile patients.
Symptoms of MLD
Damage to the protective myelin covering the nerves results in progressive worsening of brain and nervous system functions, including:
Loss of the ability to detect sensations, such as touch, pain, heat and sound
Loss of intellectual, thinking and memory skills
Loss of motor skills, such as walking, moving, speaking and swallowing
Stiff, rigid muscles, poor muscle function and paralysis
Loss of bladder and bowel function
Gallbladder problems
Blindness
Hearing loss
Seizures
Emotional and behavioral problems, including unstable emotions and substance misuse
Each form of metachromatic leukodystrophy occurs at a different age and can have different initial signs and symptoms and rates of progression:
Late infantile form. This is the most common form of metachromatic leukodystrophy, starting around 2 years of age or younger. Progressive loss of speech and muscle function occurs rapidly. Children with this form often do not survive beyond childhood.
Juvenile form. This is the second most common form and starts in children between 3 and 16 years of age. Early signs are behavior and cognitive problems and increasing difficulty in school. Loss of the ability to walk may occur. Although the juvenile form doesn't progress as fast as the late infantile form, survival is generally less than 20 years after symptoms begin.
Adult form. This form is less common and typically starts after age 16. Signs progress slowly and may begin with behavior and psychiatric problems, drug and alcohol misuse, and issues with school and work. Psychotic symptoms such as delusions and hallucinations may occur. The course of this form varies, with periods of stable symptoms and periods of rapid decline in functioning. Adults may survive for several decades after initial symptoms.
Cause of MLD
Metachromatic leukodystrophy is an inherited disorder caused by an abnormal (mutated) gene. The condition is inherited in an autosomal recessive pattern. The abnormal recessive gene is located on one of the nonsex chromosomes (autosomes). To inherit an autosomal recessive disorder, both parents must be carriers, but they do not typically show signs of the condition. The affected child inherits two copies of the abnormal gene — one from each parent.
The most common cause of metachromatic leukodystrophy is a mutation in the ARSA gene. This mutation results in a lack of the enzyme that breaks down lipids called sulfatides that build up in the myelin.
Rarely, metachromatic leukodystrophy is caused by a deficiency in another kind of protein (activator protein) that breaks down sulfatides. This is caused by a mutation in the PSAP gene.
The buildup of sulfatides is toxic, destroying the myelin-producing cells — also called white matter — that protect the nerves. This results in damage to the function of nerve cells in the brain, spinal cord and peripheral nerves
"Rare Diseases South Africa is excited to hear about this new development and the priority review the product will receive as patients with this condition have had limited interventions available to them for many years. We hope that innovative drugs on this nature will receive the same sense of urgency from local authorities when it comes to market access, to ensure our citizens
are not left behind." ~ Kelly du Plessis, CEO, Rare Diseases South Africa