PHILADELPHIA ( TheStreet) -- Fabry disease patients treated with Amicus Therapeutics' ( FOLD) experimental pill migalastat exhibited improvements in the size of their hearts and fewer disease-related events compared to similar patients treated with currently approved injectable therapies.
The new migalastat data compliment earlier results from a successful phase III study announced in August. New and previously announced results from the migalastat phase III study in Fabry patients were presented Saturday at the American Society of Nephrology annual meeting.
Amicus is meeting with European regulators later this quarter to finalize plans to submit migalastat for approval. A similar meeting with the FDA will likely be held in the first quarter of next year, Amicus said.
Fabry is an inherited disease affecting about 10,000 people worldwide in which a genetic mutation stops an enzyme from breaking down a fatty substance known as globotriaosylceramide, or GL3. The buildup of GL3 in blood vessels throughout the body causes severe damage to kidneys, heart, brain, and other organ systems. Current Fabry treatments -- Fabrazyme, marketed by the Genzyme unit of Sanofi ( SNY) and Shire's ( SHPG) Replagal -- are injections which replace the patient's misshapen or missing native enzyme and clears GL3 from the body.
In the Amicus study, Fabry patients who were switched to migalastat, a pill taken every other day, from Fabrazyme or Replagal showed a statistically significant decrease in left ventricular mass index (LVMi) compared to patients who remained on the injectable therapies after 18 months. LVMi measures the size of the heart. Fabry patients often have enlarged hearts, which leads to cardiovascular complications and death. Approximately one-third of the Fabry patients entered the study with abnormal LVMi measurements. The percentage of these patients achieving normal LVMi levels after 18 months was not disclosed.
The Fabry patients in the study continue to be followed to determine if improvements in LVMi lead to lower incidences of cardiovascular adverse events or death, said Amicus CEO John Crowley.
Treatment with migalastat was also associated with a lower incidence of Fabry-related clinical events compared to Fabrazyme or Replagal by a margin of 29% to 44%, although the difference was not statistically significant. On all the components of the Fabry-associated clinical events score -- cardiac, kidney and central nervous system -- migalastat-treated patients reported fewer events than the injectable therapies.
Amicus's migalastat takes a different approach to treating Fabry disease compared to Fabrazyme or Replagal. The drug is a "chaperone" which accompanies, or fixes, a patient's native enzyme. Without the migalastat chaperone, the native enzyme in a Fabry patient doesn't work well and can't get to the place in a cell where it's needed to break down GL3. But with migalastat as a helper, the native enzyme is stabilized and has increased cellular activity so it can break down GL3. Migalastat doesn't work unless enough native enzyme is present, which is why Fabry patients with too little native enzyme or badly mutated enzyme don't benefit. Amicus estimates migalastat could be an effective therapy for between 30-50% of Fabry patients.
As reported last August, in the phase III study, 60 Fabry patients with amenable mutations were treated for at least 12 months with either Fabrazyme or Replagal. Thirty-six patients were then switched to migalastat and the remaining 24 patients remained on their currently approved enzyme replacement therapy. The patients were followed for 18 months, after which two measures of kidney function -- estimated GFR and measured GFR -- found migalastat to be statistically equivalent to the enzyme replacement therapies, meeting the co-primary endpoints of the study. In addition, levels of plasma lyso-Gb3, a biomarker used to assess Fabry progression, remained low and stable across both arms of the study.