Pombiliti + Opfolda approved in Japan for adults with LOPD
Nation joins EU, U.S., several other countries in backing therapy
Pombiliti + Opfolda (cipaglucosidase alfa/miglustat) has been approved for adults with late-onset Pompe disease (LOPD) by Japan’s Ministry of Health, Labour and Welfare (MHLW).
“We are delighted that we will now be able to offer a compelling new treatment option to patients living with late-onset Pompe disease in Japan,” Bradley Campbell, president and CEO of treatment developer Amicus Therapeutics, said in a company press release. “We are grateful to the MHLW and to Japan’s Pompe community, including the patients, families, and physicians who participated in our clinical studies, for their collaboration.”
With this decision, Japan joins the U.S., U.K., European Union (EU), and several other countries that have already approved the therapy for LOPD. In the U.S., only people who aren’t improving on their current enzyme replacement therapy (ERT) may use Pombiliti + Opfolda.
Phase 3 trial results supported approval
In Pompe disease, a rare genetic condition, the complex sugar molecule glycogen builds up inside cells, affecting organ and tissue function. This is caused by having no or defective acid alpha-glucosidase (GAA), an enzyme. In LOPD, symptoms begin after the first year of life.
Using ERTs to increase levels of working GAA is the current standard in the treatment of Pompe. Pombiliti + Opfolda is a two-part therapy containing a working version of GAA — Pombiliti, given as intravenous, or into-the-vein, infusions — and the stabilizer Opfolda, which is given orally and stabilizes the enzyme so it stays active in the body longer.
One-year results from the Phase 3 PROPEL trial (NCT03729362) supported approval of this combination in Japan and elsewhere. In PROPEL, Pombiliti + Opfolda was compared to alglucosidase alfa, sold as Lumizyme in the U.S. and Myozyme elsewhere, the first approved ERT. The study included 123 adult participants at sites across the world.
Specifically, the combination treatment increased the distance walked in six minutes, a standard test of exercise capacity, compared to alglucosidase alfa. However, this improvement was only significant in the subset of participants who were on ERTs before the start of the trial.
Lung function also declined significantly less during follow-up for participants in the Pombiliti + Opfolda group.
Ongoing studies test Pombiliti + Opfolda in children
The benefits of Pombiliti + Opfolda were generally maintained at two years of treatment in an open-label extension study. There was also a reduction in levels of biomarkers of muscle damage and toxic glycogen buildup.
Recent analysis indicated individuals who switched from alglucosidase alfa to Pombiliti + Opfolda in PROPEL saw improvement or stabilization of motor function, muscle strength, and lung function. Participants who remained on alglucosidase alfa remained stable or worsened on most outcomes.
Safety profiles of Pombiliti + Opfolda and alglucosidase alfa were similar in PROPEL. About one-quarter of participants on both therapies experienced reactions associated with infusion.
In two ongoing Phase 3 studies, Amicus is testing Pombiliti + Opfolda in children. The ZIP study (NCT03911505) is focused on individuals with LOPD, while the ROSSELLA study (NCT04808505) focuses on infantile-onset Pompe disease. ROSSELLA is currently recruiting at sites in the U.S., U.K., EU, and Taiwan.
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