Decision comes a day after the agency charged Genzyme with a $175 million disgorgement fee.
FDA gave Genzyme’s Lumizyme (alglucosidase alfa), produced at the 4000 L scale at its manufacturing facility in Geel, Belgium, the go-ahead to treat patients ages eight years and older with late-onset Pompe disease. Sanction comes just a day after Genzyme confirmed being slapped with a $175 million disgorgement fee and inked a consent decree with the FDA to correct violations at its Allston Landing, MA, facility.
The Allston plant produced the only other treatment for Pompe disease available in the U.S., Myozyme, which is also alglucosidase alfa but produced at the 160 L scale. Also manufactured at a facility in Framingham, MA, the drug has been in short supply due to the shut-down of the Allston plant last year after the company found viral contamination in one of its bioreactors. Later inspections by the FDA brought to light further contamination issues, which resulted in the $175 million fine and consent decree.
Due to limited manufacturing capacity, Genzyme reserved Myozyme to treat infants and children in the U.S. with Pompe disease because younger patients generally have a much more aggressive form of the disease. Last week, the firm received regulatory approval to fill and finish Myozyme produced at the 160 L scale at its facility in Waterford, Ireland, and will no longer be conducting fill/finish operations for Myozyme in Allston. Some adult patients in the U.S. received Lumizyme under a temporary access program.
Genzyme says that it has invested nearly $1 billion to support its Pompe disease development program. In 2006, it received approval for Myozyme manufactured at the 2000 L bioreactor scale in Europe and some countries outside of the U.S. to treat all patients with Pompe disease. At this time, Genzyme also received FDA approval for Myozyme manufactured at the 160 L bioreactor scale in the U.S.
In 2009, Genzyme received approval outside of the U.S. to manufacture Myozyme in 4000 L bioreactors at its facility in Geel. The firm then began to transition patients globally to the product manufactured at this larger scale. To prepare for growing demand for alglucosidase alfa, Genzyme has installed a third 4000 L bioreactor in Geel with an anticipated approval in 2011.
Today’s U.S. approval of the 4000 L bioreactor scale comes with a risk evaluation and mitigation strategy and will only be available through a restricted distribution system called the Lumizyme ACE (alglucosidase alfa control and education) Program to ensure that it is used by the correct patient group. It is specifically indicated for those who do not have evidence of cardiac hypertrophy. The drug will also carry a boxed warning stating the risk of anaphylaxis, severe allergic reactions, and immune-mediated reactions.
The safety and efficacy of Lumizyme are based on a clinical study in 90 patients, ages 10 to 70 years, with late-onset Pompe disease. The most commonly reported side effects for Lumizyme were infusion-related reactions and included severe allergic reactions, hives, diarrhea, vomiting, shortness of breath, itchy skin, skin rash, neck pain, partial hearing loss, flushing, pain in extremities, and chest discomfort.
In Pompe disease, a gene mutation prevents the body from making the enzyme—or making enough of the enzyme—called acid alpha-glucosidase (GAA). GAA is necessary for proper muscle functioning and is used by the heart and muscle cells to convert a form of sugar called glycogen into energy. Without the enzyme action, glycogen builds up in the cells and ultimately weakens the heart and muscles. Lumizyme is believed to work by replacing the deficient GAA, thereby reducing the accumulated glycogen in heart and skeletal muscle cells.