- Encouraging results from a closely watched early-stage study of Amicus Therapeutis Inc's Pompe disease candidate could position the experimental therapy as a potentially best-in-class treatment for the inherited neuromuscular disease.
- Amicus' therapy, which replaces a key enzyme missing in people with Pompe disease, helped nearly all patients in the study walk longer after six months of treatment, and broadly improved muscle function in those patients already wheelchair-bound.
- Investor optimism about the treatment's potential had appeared to largely offset disappointment from last month's clinical setback for another of Amicus' rare disease candidates. Now, with positive results in hand, Amicus hopes to advance the Pompe disease therapy into a Phase 3 study or — pending discussions with regulators — a potential filing for conditional approval.
Pompe disease is an inherited lysosomal storage disorder triggered by deficiency in a key enzyme that breaks down a sugar known as glycogen. Without this enzyme, glycogen builds up in the muscles of Pompe patients, leading to progressive muscle weakening. Over time, affected patients lose the ability to walk or hold objects, eventually leading to difficulties swallowing or completing other critical functions.
Current treatment options include enzyme replacement therapies like Sanofi SA's Lumizyme (alglucosidase alfa). Efficacy remains limited however, and ultimately plateaus.
Amicus designed its therapy, known as ATB200, to better target and be absorbed by affected muscles. To accomplish this, the biotech paired a recombinant human enzyme with a pharmacological "chaperone," which is given to patients before infusion of the treatment. The chaperone stabilizes and protects the enzyme in the blood. In previous studies, this partner drug helped increase enzyme present in the muscle and reduce glycogen levels.
Results from Amicus' small open-label study published Wednesday showed treatment led to improved muscle function in 16 out of 18 patients at the six-month mark, and in all 10 patients assessed through month nine.
On a key measure known as the six-minute walk test, patients in the study who had never received enzyme replacement therapy walked an average of nearly 42 meters further at six months than they did when beginning treatment. Patients who switched to ATB200 from previous therapy saw an average 35 meter improvement.
Benefit seemed to grow with time, although fewer patients were tested at nine months.
"We were positively surprised that we saw the magnitude and consistency of change in people who had been on [other enzyme replacement therapy] for many years," Amicus' CEO John Crowley said in an interview.
ATB200 also exceeded analyst expectations of a 20 to 30 meter improvement in switch patients and a 35 meter or greater improvement in treatment-naive patients.
Notably, the functional improvement seen was complemented by data showing lower levels of certain biomarkers associated with muscle damage — a point that Crowley says reinforces the clinical profile of Amicus' therapy.
On measures of pulmonary function, treatment appeared to deliver less of a benefit, although most patients either remained stable or improved slightly.
In light of the results, Amicus hopes to advance its Pompe therapy quickly. "We are committed to working collaboratively with regulators to determine the fastest regulatory pathways that may be available to bring this new treatment paradigm to as many patients living with Pompe disease globally, as quickly as possible," said Crowley in a statement released Wednesday morning.
In that statement, Amicus said it would provide an update on its path forward sometime in the first half of next year.
Amicus has already been the beneficiary of a more friendly Food and Drug Administration. The agency had previously said it would require an additional Phase 3 trial for Amicus' Fabry disease drug migalastat. But after Commissioner Scott Gottlieb took office, the regulator dropped its requirement and allowed Amicus to file for approval with the data it currently has.
If Amicus' Pompe treatment makes it across the regulator's desk, it could carve out a profitable market. Last year, Sanofi earned roughly €725 million in sales of Lumizyme, which is marketed as Myozyme in Europe. A strong safety profile and potentially superior efficacy for ATB200 could help Amicus make inroads in the future.