Pombiliti Plus Opfolda Approved for Late-Onset Pompe Disease

The Food and Drug Administration (FDA) has approved Pombiliti^™ (cipaglucosidase alfa-atga) in combination with Opfolda^™ (miglustat) for the treatment of adults with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing at least 40kg and who are not improving on their current enzyme replacement therapy.

Pompe disease is a rare, degenerative muscle disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). GAA deficiency results in intra-lysosomal accumulation of glycogen in various tissues and subsequent organ impairment.

Pombiliti plus Opfolda is a 2-component therapy. Cipaglucosidase alfa-atga provides an exogenous source of GAA, while miglustat, an enzyme stabilizer, reduces loss of enzyme activity in the blood.

The approval was based on data from the double-blind, active-controlled, phase 3 PROPEL trial (ClinicalTrials.gov Identifier: NCT03729362), which included 123 adults with late-onset Pompe disease who still had the ability to walk and breathe without mechanical ventilation. Patients were randomly assigned 2:1 to receive either cipaglucosidase alfa-atga plus miglustat or alglucosidase alfa, an enzyme replacement therapy. The primary endpoint was the change from baseline in 6-minute walk distance (6MWD) at week 52.

Results showed that patients treated with cipaglucosidase alfa-atga plus miglustat walked on average 21 meters farther from baseline compared with 8 meters for those treated with alglucosidase alfa (treatment difference, 14 meters [95% CI, -1, 28]). Among ERT-experienced patients, the cipaglucosidase alfa-atga plus miglustat arm experienced a numerically favorable change in 6MWD at week 52 (nominal P =.047). 

At week 52, patients treated with cipaglucosidase alfa-atga plus miglustat experienced a mean change in sitting forced vital capacity (FVC) of -1.1% compared with -3.3% for alglucosidase alfa-treated patients (estimated treatment difference, 2.3% [95% CI, 0.02-4.62]). Among ERT-experienced patients, the cipaglucosidase alfa-atga plus miglustat arm showed a numerically favorable change in sitting FVC at week 52 (nominal P =.006).

The most common adverse reactions reported with cipaglucosidase alfa-atga plus miglustat were headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia. The prescribing information for Pombiliti includes a boxed warning regarding the potential for severe hypersensitivity reactions and infusion-associated reactions, as well as a risk of acute cardiorespiratory failure in susceptible patients.

Pombiliti is supplied as 105mg of cipaglucosidase alfa-atga as a lyophilized powder in a single-dose vial for reconstitution. Opfolda is supplied as 65mg capsules. Both products are expected to launch immediately.

Amicus Therapeutics is offering a support program for eligible patients through Amicus Assist.