UK Gives Eligible Late-onset Pompe Patients Early Access to AT-GAA

AT-GAA, an investigational therapy by Amicus Therapeutics for late-onset Pompe disease, will be available to select patients in the U.K. through an early access program before its potential regulatory approval.

Eligible patients are adults who have received the enzyme replacement therapy (ERT) alglucosidase alfa — the current standard Pompe treatment marketed as Myozyme in Europe and Lumizyme in the U.S. — for at least two years.

The Early Access to Medicines Scheme in the U.K. gives people with life-threatening or seriously debilitating conditions and a clear unmet medical need access to therapies not yet approved for commercial use.

“Alternative treatment options that have the potential to have a meaningful impact in managing this devastating neuromuscular disease are desperately needed, and this decision will allow eligible patients access to AT-GAA at the earliest opportunity,” Mark Roberts, MD, consultant neurologist at the Greater Manchester neurosciences unit at Salford Royal NHS Foundation Trust, in the U.K., said in a press release.

Allan Muir, chair of the board of trustees of the U.K.-based Pompe Support Network, said that “with significant unmet needs and a lack of treatment choices for people living with Pompe disease in the UK, we are closer to a new option for patients.”

“Amicus has been a true partner for the Pompe community for more than a decade, and I look forward to potentially having a new therapy available in the UK,” Muir added.

The decision was based on a positive scientific opinion granted by the country’s Medicines and Healthcare Products Regulatory Agency (MHRA).

Standing for at least one year, the opinion provides physicians with information on the therapy’s benefit-risk balance based on available data to help them decide whether or not to prescribe an unapproved treatment.

John F. Crowley, Amicus’s chairman and CEO, said that this opinion reaffirms the “significant unmet medical need in Pompe disease today, and supports our strategy of advancing AT-GAA as quickly as possible to as many patients as possible.”

“We are privileged to offer eligible patients in the UK access to this novel medicine prior to marketing authorization, reinforcing our commitment to people living with Pompe and other rare diseases,” he added.

Amicus plans to file regulatory applications with health authorities in the U.K. and in the European Union in the second half of this year, seeking the approval of AT-GAA for late-onset Pompe disease.

In the U.K., the company will seek AT-GAA’s approval for all late-onset Pompe disease patients, regardless of whether they received Myozyme treatment or for how long.

A similar application is expected to be filed with the U.S. Food and Drug Administration by late June. Initiated in December 2020, the rolling application allows Amicus to submit completed sections of the application as soon as they are ready, instead of waiting to file the entire document at once, as is typically done.

The therapy received a priority innovative medicines designation in the U.K. and breakthrough therapy designation in the U.S. for late-onset Pompe; both are meant to accelerate its development and regulatory review.

AT-GAA combines cipaglucosidase alfa, a lab-made version of the missing enzyme in Pompe that was designed to enter cells more effectively, with miglustat, which stabilizes the enzyme’s structure.

Cipaglucosidase alfa is administered directly into the bloodstream, while miglustat (sold as Zavesca for the treatment of Gaucher disease) is taken as an oral capsule.

By providing the missing enzyme to patients’ cells, the therapy is designed to prevent further damage associated with Pompe’s toxic accumulation of glycogen in several tissues, particularly muscles. Glycogen is a large sugar molecule used for energy storage.

MHRA’s decision to provide adult Pompe patients early access to AT-GAA was mainly based on positive data from the open-label Phase 1/2 ATB200-02 trial (NCT02675465) and the Phase 3 PROPEL study (NCT03729362). Most patients in these studies had previously received standard ERT, alglucosidase alfa.

ATB200-02’s results showed that two years of treatment with AT-GAA improved the muscle strength and motor function of adults with Pompe disease, while stabilizing or improving their lung function.

PROPEL evaluated the safety and effectiveness of AT-GAA against alglucosidase alfa plus placebo capsules in 123 adults with late-onset Pompe disease — making it the largest placebo-controlled trial in Pompe disease.

Top-line data highlighted the presence of significant gains in physical and lung function among people switching from standard ERT to AT-GAA, but not in those who continued on alglucosidase alfa.

AT-GAA-treated patients also showed muscle and motor function improvements, reductions in muscle damage biomarkers, and increased glycogen clearance, compared with those given the standard treatment. However, not all group differences reached statistical significance.

All of PROPEL’s participants chose to enter an open-label extension study, in which all are receiving the experimental therapy for longer periods.

AT-GAA is also being evaluated in the Phase 3 ZIP study (NCT03911505), which is enrolling children and adolescents with late-onset Pompe disease at sites in the U.S., Canada, Japan, and Taiwan.

In addition, Amicus plans to test the therapy in up to 22 patients, from birth to 17 years old, with classic infantile-onset Pompe disease in an upcoming Phase 3 trial, named Rossella (NCT04808505). The trial is not yet recruiting but is expected to start in August.