Amicus Therapeutics Rare Disease Combo Therapy Wins Long-Awaited FDA Nod

Amicus Therapeutics Rare Disease Combo Therapy Wins Long-Awaited FDA Nod


An Amicus Therapeutics combination treatment for the rare enzyme deficiency Pompe disease now has FDA approval, giving the drugmaker the opportunity to help patients who don’t respond to Sanofi products that are currently the standard of care.

In Pompe disease, patients lack acid alpha-glucosidase (GAA), an enzyme that breaks down a sugar called glycogen. The resulting GAA buildup damages muscles, leading to walking difficulties and progressively worsening respiratory problems. FDA approval of the Amicus therapy announced Thursday covers the treatment of adults with late-onset Pompe who are not improving from their current enzyme replacement therapy.

Philadelphia-based Amicus takes a two-pronged approach to Pompe. Cipaglucosidase alfa-atga, brand name Pombiliti, is an engineered version of the deficient enzyme administered as an intravenous infusion. That product is administered alongside miglustat, brand name Opfolda. This small molecule, taken as a tablet, doesn’t do anything to break down glycogen. Instead, it stabilizes Pombiliti in the blood, enabling muscle cells to better take in the engineered enzyme.

“Over the past decade, we have compiled a body of clinical evidence, for Pombiliti and Opfolda, that demonstrate improvement in [enzyme replacement therapy]-experienced adults,” Amicus President and CEO Brad Campbell said during a conference call Thursday. “We are confident that the consistency and durability of effect in patients across key manifestations of the disease illustrates the potential impact Pombiliti and Opfolda can have for many individuals.”

The standard Pompe enzyme replacement treatment is Sanofi’s Lumizyme. The FDA approval of Pombiliti and Opfolda is based on the results a Phase 3 study that compared the combination treatment to Lumizyme and a placebo. The main goal was to show the change in walking distance in a six minute walk test, measured at baseline and after 52 weeks of treatment. On average, patients treated with the Amicus drug combination showed a 21 meter improvement compared to seven meters in the Lumizyme group. While the change was numerically greater, it was not enough to be statistically significant.

Despite falling short of the main study goal, the trial results showed a statistically significant improvement in forced vital capacity, a lung function measure that was a key secondary goal. Furthermore, subsequent data reports from an open-label extension study showed that in those treated up to two years, the improvements in muscle function, walking, and breathing continued. The results also showed reduction in biological indicators of muscle damage.

Because Amicus’s Pompe therapy comprised of two separate drugs that each work differently, the company in 2021 submitted separate applications for each one. Both were expected to receive FDA decisions in 2022, but the FDA last year extended the review period. Last fall, the FDA again extended the review, citing the inability to complete inspections of the therapy’s manufacturing facility due to Covid-19 travel restrictions.

In an investor presentation, Amicus said it expects the Pompe combination treatment will become available within two weeks.

Amicus estimates the current U.S. Pompe market represents a more than $500 million opportunity; $1.2 billion globally. Pombiliti and Opfolda received European Union approval earlier this year. Amicus projects the Pompe combo treatment could achieve peak sales of about $1 billion. The approval covers patients who have previously been treated with Lumizyme or Nexviazyme (Nexviadyme in Europe), a next-generation Pompe enzyme replacement therapy that Sanofi designed for better cellular uptake.

On measures of safety, the Amicus treatment was comparable to Sanofi’s. Pombiliti’s label carries a black box warning that flags the risk of hypersensitivity reactions including anaphylaxis, infusion-associated reactions, and potential acute cardiorespiratory failure in those who have underlying respiratory or heart problems. Both Sanofi products carry similar warnings.

Pombiliti and Opfolda together represent Amicus’s second commercialized therapy. The company’s first product, Galafold, treats Fabry disease, a different rare enzyme deficiency. The Pompe combination treatment is dosed according to patient weight. Campbell said the two products together will carry a list price of about $650,000 annually for a patient weighing 60 kilograms (about 132 pounds), which is a modest discount to the currently available enzyme replacement therapies. He added that similar to Galafold, Amicus commits to not raising the price any higher than increases to the consumer price index in order to maintain broad access to the treatment.

Photo by FDA



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