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The FDA approved the two-component therapy of cipaglucosidase alfa (Pombiliti) plus miglustat (Opfolda) for adults with late-onset Pompe disease who see no improvement on enzyme replacement therapy (ERT), on Thursday.

A rare genetic lysosomal disorder, Pompe disease is caused by a deficiency of the acid alpha-glucosidase (GAA) enzyme. Reduced GAA leads to glycogen build-up in skeletal and muscle tissue, causing muscle damage that can ultimately lead to respiratory problems and heart failure.

Cipaglucosidase alfa is a recombinant human GAA enzyme that can break down glycogen, while miglustat helps stabilize the enzyme in the blood.

Findings from 123 patients in the provided the primary support for approval, despite missing for statistical significance on its primary endpoint -- an improvement in 6-minute walk distance -- in the overall population of patients with and without prior ERT. Participants had a mean age of 47 years, 54% were women, and 85% were white.

About three-fourths had prior ERT exposure. In these patients, mean change from baseline in 6-minute walk distance was numerically superior at 52 weeks with the two-drug therapy compared with alglucosidase alfa plus placebo (16 m vs 1 m).

And for the key secondary endpoint of forced vital capacity (% predicted) while sitting at 52 weeks, the study group showed stabilization as compared with a decline in the control group (0.1% vs -3.5%, respectively).

"The Pompe community continues to face unmet need and limited treatment options," said PROPEL investigator Tahseen Mozaffar, MD, of University of California Irvine, in a statement from the drugmaker.

"This two-component therapy is an important new treatment for those adults living with late-onset Pompe disease and not improving on current therapies," he continued. "I am encouraged by the evidence generated over many years of clinical research studying this therapy for ERT-experienced patients living with late-onset Pompe disease."

Safety data from PROPEL showed that nearly all patients, regardless of treatment assignment, experienced treatment-emergent adverse events (AEs). The most common AEs with cipaglucosidase alfa plus miglustat included falls (29%), headache (24%), nasopharyngitis (22%), myalgia (16%), and arthralgia (15%). One serious AE -- a case of anaphylaxis -- was deemed related to treatment.

for cipaglucosidase alfa includes boxed warnings over the risks for hypersensitivity reactions (including anaphylaxis), infusion-related reactions, and acute cardiorespiratory failure in susceptible patients, and the therapy is contraindicated in pregnant patients due to the risks for embryo-fetal toxicity.

The two-component therapy is specifically indicated for adults who weigh at least 40 kg (88 lb), with a recommended cipaglucosidase alfa dosage of 20 mg/kg every other week (delivered intravenously over 4 hours) in combination with miglustat. The prescribing information recommends that patients start 2 weeks after their last dose of ERT and also receive antihistamines, antipyretics, and/or corticosteroids before administration.

As the two-component therapy is already approved abroad, Amicus Therapeutics said it would launch the product in the U.S. immediately.

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