FDA Approves Pombiliti Plus Opfolda for Late-Onset Pompe Disease
[ad_1]
Pompe disease, a rare genetic disorder that causes severe and often life-threatening heart and lung problems in newborns and young children — and which can also occur later in life, causing progressive muscle and breathing dysfunction in children, teens, and adults — has historically had few viable treatment options.
However, that has started to change in recent years with the advent of enzyme replacement therapy (ERT) — and now, this category of treatments has expanded with the U.S. Food and Drug Administration (FDA) approval, on September 28, 2023, of Pombiliti plus Opfolda, a combination of the drugs cipaglucosidase alfa (Pombiliti) and miglustat (Opfolda).
The new drug combination is specifically approved for adults weighing at least 40 kilograms (88 pounds) who are not improving on their current enzyme replacement therapy.
“This is a potential lifesaving therapy for Pompe disease, yet it has limitations,” says Priya S. Kishnani, MD, medical director of the Y.T. and Alice Chen Pediatrics Genetics and Genomics Center at Duke University Medical Center in Durham, North Carolina, and an expert in Pompe disease. “Like other next-generation therapies, it allows for better targeting to the skeletal muscles,” which are adversely affected by the disorder.
‘Breakthrough Therapy’ Designation Speeds Drug Development
Pombiliti plus Opfolda was designated as a breakthrough therapy by the FDA, which means that it treats a serious condition and that preliminary clinical evidence suggests it “may demonstrate substantial improvement over available therapy,” according to the agency.
The designation is intended to expedite the development and review of drugs that qualify.
Pompe disease, which occurs in roughly 1 in 40,000 people in the general population, according to the National Organization for Rare Disorders, is caused by the body’s inability to break down glycogen, a stored form of glucose, due to a deficiency in an enzyme called acid alpha-glucosidase (GAA). As glycogen builds up in the cells in the body, it adversely affects muscle, organ, and tissue development.
This can lead to poor muscle development and weakness as well as heart and lung problems and damage to organs such as the liver and spleen. Many people with Pompe disease require supplemental oxygen or mechanical ventilation to maintain breathing as their symptoms progress.
Currently, there’s no cure for the disorder, though ERT can manage symptoms and slow progression in some of those affected.
Most people with the disorder first experience symptoms during infancy, or within a few months of birth, and often don’t live past early childhood.
However, others may not have symptoms until later in childhood or even adulthood.
Developed by drug manufacturer Amicus Therapeutics, Pombiliti plus Opfolda is a form of ERT intended to treat this latter group, or those with what’s known as late-onset Pompe disease.
New Drug Combines an Enzyme With an Enzyme Stabilizer
Pombiliti plus Opfolda contains two primary ingredients: cipaglucosidase alfa — a man-made form of the GAA enzyme designed to effectively enter muscle cells — and miglustat, a drug that works to stabilize the man-made enzyme so that it remains active over a longer period (similar to an extended-release formulation of a medication).
The treatment is administered in two separate components: Cipaglucosidase alfa is given via infusion into the bloodstream, at a dose of 20 milligrams per kilogram of body weight, while miglustat is taken in tablet form, by mouth, at a dose of 260 milligrams. Both are administered every other week.
The therapy is expected to cost about $650,000 a year for a person weighing about 70 kilograms, according to Reuters.
Phase 3 Trial Show Better Lung Function and Walking Ability
In a phase 3 clinical trial, published in December 2021 by the journal The Lancet Neurology, Pombiliti plus Opfolda enhanced walking ability and improved or stabilized lung function within one year of starting treatment in 85 adults with Pompe disease. However, those treated with the new drug were more likely to experience side effects such as falls, headaches, cold-like symptoms, and muscle and joint pain, compared with study participants given another form of ERT, alglucosidase alfa.
A phase 3 clinical trial is the final stage of the drug research and development process prior to FDA approval.
Virginia Kimonis, MD, a professor of pediatric genetics and genomic medicine at the University of California in Irvine, says the approval of Pombiliti plus Opfolda is “very significant,” given that there’s currently no cure for Pompe disease and that existing therapies have historically had limited effect on symptoms and progression.
It appears to be “more effective” than existing treatments and may be particularly helpful for those whose health “may be deteriorating” due to ongoing disease progression, she adds.
[ad_2]
