Fabry Disease Patients Get Sicker as Drugs Go Overseas

Aug. 30, 2011— -- Jerry Walter, a semi-retired Army colonel who lives in North Carolina, said he has led a "charmed life," surviving the terrorist attack on the Pentagon in 2001 and two life-threatening bacterial infections.

At 56, Walter has also outlived a brother and two other relatives who, like him, had Fabry disease, a rare genetic disorder that can wreak havoc on the kidneys and cause strokes and early death. Caused by the lack of an enzyme --- alpha-galactosidase-A -- which is required to metabolize lipids or fatlike substances in the body, its symptoms include chronic gastrointestinal and cardiovascular problems, pains in the hands and feet, renal failure, as well as skin and eye complications, according to the National Institutes of Neurological Disorders and Stroke.

Since 2003, the expensive drug Fabrazyme has kept Walter alive, but since 2009, Fabrazyme has been in short supply, and his dosage has been cut in half.

" target="_blank">arrhythmia after the shortages," said Walter, who is founder of the National Fabry Disease Foundation.

Jeanette, 33, of Royal Oak, Mich., is currently recovering from a stroke after going two years without full dosages of Fabrazyme.

"I am hanging in there, but I have trouble with my speech," said Jeanette, who did not want to use her last name, and is on disability. "It's crazy. I talked to the FDA, but they can't force a drug manufacturer to do anything."

Since early August, Genzyme, the manufacturer of Fabrazyme, has not been able to ship the drug to an estimated 1,200 Americans with the disease, and now patients fear that shipments will be stopped altogether in September.

Now Jeannette is one of 14 patients who are suing Genzyme for physical damages because of the drug's unavailability. They have also petitioned the Food and Drug Administration to impose a ban on the sale of the drug outside the United States -- Europeans are receiving full dosages of Fabrazyme as Americans get sicker. Genzyme did not wish to comment on the lawsuit.

Their lawyer, C. Allen Black of Pittsburgh, said many more will soon be joining the litigation.

"This is one of the worst avoidable tragedies in American medicine, and the suffering has been incalculable," according to Black, who said patients are suing for millions of dollars in damages because they are so sick they cannot work. The drugs cost $30,000 for each infusion, and a full dose consists of two infusions a month.

Genzyme's problems began in June 2009 when the only plant that manufactured the biological drug was shut down in Allston, Mass., by the FDA because of virus contamination

The company was fined $175 million and issued a consent decree to remediate. The French pharmaceutical giant Sanofi-Aventis took over the company in April.

Genzyme admitted to miscalculations in its drug reserves, which caused it to cut back on supplies of Fabrazyme to patients, but it said the shortage would eventually be resolved.

"People who work at Genzyme feel a close connection with patients," said Bo Piela, vice president of corporate communications at the pharmaceutical company. "We understand the impact that the Fabrazyme shortage has had on patients and their families. Our highest priority is to restore full supplies of the medicines we make. We are doing everything possible to achieve this and are making good progress toward the approval of a second manufacturing plant that will allow us to significantly increase product supply."

A similar drug, Replagal, which is marketed in Europe by the biopharmaceutical company Shire,

has not been approved for sale in the United States. About 100 Americans with Fabry disease are receiving Replagal through an investigational clinical trial sanctioned by the FDA

"Unfortunately, Shire withdrew its application for FDA approval [of Replagal], so, there is not much we can do to force Shire to make it available in the U.S.," said Black. "The only solution for U.S. patients is to increase the production of Fabrazyme."

Debra Lewis, acting director of the FDA's Office of Orphan Products Development, said the agency gives exclusive marketing to drugs for seven years, and Genzyme's rights to Fabrazyme expired in April 2010. "As far as the FDA is concerned, it would not limit another product," she said.

"We would welcome working with an outside company to help address the shortage," said Lewis. "We have limits to our authority, and people don't want the FDA to go beyond its charge to see if a product is safe and effective."

In the meantime, patients like Walter report a steep decline in their health -- heart enlargement, kidney failure and neurological problems. They are also worried about reports from Europe of health risks associated with reducing medication.

In a 2010 letter from Genzyme Europe, the company said that lowered dosages of the drugs could cause "aggravation" of disease symptoms and or "adverse events" -- "pain, cardiac manifestations and deafness."

"This story should scare the hell out of everyone in America," said Black, the lawyer. "There's a lot of monopoly out there. It could have hit insulin production or chemotherapy."

In all, 18 members of Walter's family have been affected by the X-linked genetic disorder. Men with the gene can pass it on to their daughters. Women with the gene have a 50-50 chance of passing it on to their sons or daughters.

The average age of death for an untreated male is 50, according to Walter, whose brother died at 37. He said the drug had been a godsend, but now Fabry patients feel abandoned.

"I was down to a third of a dose at one point, and now I am back to a half, but recently the shipments have been on hold completely with no expected date to return to shipping," said Walter.

Genzyme's Piela said that despite delays, August doses will be available to patients soon. "However, we do not expect to ship Fabrazyme to meet this allocation until September," he said.

"These are biologic drugs, and there is variability in production based on various factors," said Piela.

The company is in the midst of constructing a second manufacturing plant in Framingham, Mass., and when that is approved "We will be able to meet full demands," he said. "But licensing takes time."

Piela said he expects production there to be in full swing by 2012 and "significantly increase capacity and help end the supply shortage."

But that isn't soon enough for patients who say they need full dosages of the drug now.

"There are really no options," said one 27-year-old New Yorker with the disease, who did not want his name used because the Fabry community is so small he fears he might not get his medication.

"Recently, [Genzyme] canceled another dose for me -- the appointment was for one of two people. I don't know if they are manually picked, and I would rather not give them a reason not to pick me again. ... I don't want to be singled out as a troublemaker." His last half dose was Aug. 3.

Now, he is considering moving to France, where he has dual citizenship and can obtain the lifesaving Fabrazyme or Replagal.

"I count my blessings," he said. "Thankfully, there's a treatment option out there."

But American patients still want to know why they cannot have the same access to full doses as patients in Europe. Genzyme officials said that the European Medicine Agency has required full dosages of Fabrazyme, and the company is complying with that "guidance."

"We provide the drug to every patient in the world that needs it," countered Genzyme's Piela. "It's an extremely rare disease, and we have been treating patients in Europe, Latin America and Asia where it's been approved.

In addition to asking the FDA to stop overseas shipments of the drug, the plaintiffs filed petitions with the National Institutes of Health to allow other manufacturers to license the patent on Fabrazyme. That was denied in December.

Patients could also ask for an executive order by President Obama. "This is extraordinarily rare and used for national defense, but I think it rises to that level," said Black.

Walter said he agrees that critical action is needed.

"It's not really fair to accuse [Genzyme] of wrongdoing for a virus, but they could have planned better and built an inventory," he said. "But now, we are not confident they are doing everything they can for the Fabry community."

His last infusion was set for Aug. 16 and never arrived; as his Aug. 30 dose approaches, Walter still doesn't know if he will be able to get it.

He called Genzyme, but said, "It's been a good two weeks with no answers yet. I am about to miss my second one in a row, and I don't know what's happening. ... We are in grave need of help."

"This is one of the worst avoidable tragedies in American medicine, and the suffering has been incalculable," according to Black, who said patients are suing for millions of dollars in damages because they are so sick they cannot work. The drugs cost $30,000 for each infusion, and a full dose consists of two infusions a month.

Genzyme's problems began in June 2009 when the only plant that manufactured the biological drug was shut down in Allston, Mass., by the FDA because of virus contamination

The company was fined $175 million and issued a consent decree to remediate. The French pharmaceutical giant Sanofi-Aventis took over the company in April.

Genzyme admitted to miscalculations in its drug reserves, which caused it to cut back on supplies of Fabrazyme to patients, but it said the shortage would eventually be resolved.

"People who work at Genzyme feel a close connection with patients," said Bo Piela, vice president of corporate communications at the pharmaceutical company. "We understand the impact that the Fabrazyme shortage has had on patients and their families. Our highest priority is to restore full supplies of the medicines we make. We are doing everything possible to achieve this and are making good progress toward the approval of a second manufacturing plant that will allow us to significantly increase product supply."

A similar drug, Replagal, which is marketed in Europe by the biopharmaceutical company Shire,

has not been approved for sale in the United States. About 100 Americans with Fabry disease are receiving Replagal through an investigational clinical trial sanctioned by the FDA

"Unfortunately, Shire withdrew its application for FDA approval [of Replagal], so, there is not much we can do to force Shire to make it available in the U.S.," said Black. "The only solution for U.S. patients is to increase the production of Fabrazyme."

Debra Lewis, acting director of the FDA's Office of Orphan Products Development, said the agency gives exclusive marketing to drugs for seven years, and Genzyme's rights to Fabrazyme expired in April 2010. "As far as the FDA is concerned, it would not limit another product," she said.

"We would welcome working with an outside company to help address the shortage," said Lewis. "We have limits to our authority, and people don't want the FDA to go beyond its charge to see if a product is safe and effective."

In the meantime, patients like Walter report a steep decline in their health -- heart enlargement, kidney failure and neurological problems. They are also worried about reports from Europe of health risks associated with reducing medication.

In a 2010 letter from Genzyme Europe, the company said that lowered dosages of the drugs could cause "aggravation" of disease symptoms and or "adverse events" -- "pain, cardiac manifestations and deafness."

"This story should scare the hell out of everyone in America," said Black, the lawyer. "There's a lot of monopoly out there. It could have hit insulin production or chemotherapy."

In all, 18 members of Walter's family have been affected by the X-linked genetic disorder. Men with the gene can pass it on to their daughters. Women with the gene have a 50-50 chance of passing it on to their sons or daughters.

The average age of death for an untreated male is 50, according to Walter, whose brother died at 37. He said the drug had been a godsend, but now Fabry patients feel abandoned.

"I was down to a third of a dose at one point, and now I am back to a half, but recently the shipments have been on hold completely with no expected date to return to shipping," said Walter.

Genzyme's Piela said that despite delays, August doses will be available to patients soon. "However, we do not expect to ship Fabrazyme to meet this allocation until September," he said.

"These are biologic drugs, and there is variability in production based on various factors," said Piela.

The company is in the midst of constructing a second manufacturing plant in Framingham, Mass., and when that is approved "We will be able to meet full demands," he said. "But licensing takes time."

Piela said he expects production there to be in full swing by 2012 and "significantly increase capacity and help end the supply shortage."

But that isn't soon enough for patients who say they need full dosages of the drug now.

"There are really no options," said one 27-year-old New Yorker with the disease, who did not want his name used because the Fabry community is so small he fears he might not get his medication.

"Recently, [Genzyme] canceled another dose for me -- the appointment was for one of two people. I don't know if they are manually picked, and I would rather not give them a reason not to pick me again. ... I don't want to be singled out as a troublemaker." His last half dose was Aug. 3.

Now, he is considering moving to France, where he has dual citizenship and can obtain the lifesaving Fabrazyme or Replagal.

"I count my blessings," he said. "Thankfully, there's a treatment option out there."

But American patients still want to know why they cannot have the same access to full doses as patients in Europe. Genzyme officials said that the European Medicine Agency has required full dosages of Fabrazyme, and the company is complying with that "guidance."

"We provide the drug to every patient in the world that needs it," countered Genzyme's Piela. "It's an extremely rare disease, and we have been treating patients in Europe, Latin America and Asia where it's been approved.

In addition to asking the FDA to stop overseas shipments of the drug, the plaintiffs filed petitions with the National Institutes of Health to allow other manufacturers to license the patent on Fabrazyme. That was denied in December.

Patients could also ask for an executive order by President Obama. "This is extraordinarily rare and used for national defense, but I think it rises to that level," said Black.

Walter said he agrees that critical action is needed.

"It's not really fair to accuse [Genzyme] of wrongdoing for a virus, but they could have planned better and built an inventory," he said. "But now, we are not confident they are doing everything they can for the Fabry community."

His last infusion was set for Aug. 16 and never arrived; as his Aug. 30 dose approaches, Walter still doesn't know if he will be able to get it.

He called Genzyme, but said, "It's been a good two weeks with no answers yet. I am about to miss my second one in a row, and I don't know what's happening. ... We are in grave need of help."

A similar drug, Replagal, which is marketed in Europe by the biopharmaceutical company Shire,

has not been approved for sale in the United States. About 100 Americans with Fabry disease are receiving Replagal through an investigational clinical trial sanctioned by the FDA

"Unfortunately, Shire withdrew its application for FDA approval [of Replagal], so, there is not much we can do to force Shire to make it available in the U.S.," said Black. "The only solution for U.S. patients is to increase the production of Fabrazyme."

Debra Lewis, acting director of the FDA's Office of Orphan Products Development, said the agency gives exclusive marketing to drugs for seven years, and Genzyme's rights to Fabrazyme expired in April 2010. "As far as the FDA is concerned, it would not limit another product," she said.

"We would welcome working with an outside company to help address the shortage," said Lewis. "We have limits to our authority, and people don't want the FDA to go beyond its charge to see if a product is safe and effective."

In the meantime, patients like Walter report a steep decline in their health -- heart enlargement, kidney failure and neurological problems. They are also worried about reports from Europe of health risks associated with reducing medication.

In a 2010 letter from Genzyme Europe, the company said that lowered dosages of the drugs could cause "aggravation" of disease symptoms and or "adverse events" -- "pain, cardiac manifestations and deafness."

"This story should scare the hell out of everyone in America," said Black, the lawyer. "There's a lot of monopoly out there. It could have hit insulin production or chemotherapy."

In all, 18 members of Walter's family have been affected by the X-linked genetic disorder. Men with the gene can pass it on to their daughters. Women with the gene have a 50-50 chance of passing it on to their sons or daughters.

The average age of death for an untreated male is 50, according to Walter, whose brother died at 37. He said the drug had been a godsend, but now Fabry patients feel abandoned.

"I was down to a third of a dose at one point, and now I am back to a half, but recently the shipments have been on hold completely with no expected date to return to shipping," said Walter.

Genzyme's Piela said that despite delays, August doses will be available to patients soon. "However, we do not expect to ship Fabrazyme to meet this allocation until September," he said.

"These are biologic drugs, and there is variability in production based on various factors," said Piela.

The company is in the midst of constructing a second manufacturing plant in Framingham, Mass., and when that is approved "We will be able to meet full demands," he said. "But licensing takes time."

Piela said he expects production there to be in full swing by 2012 and "significantly increase capacity and help end the supply shortage."

But that isn't soon enough for patients who say they need full dosages of the drug now.

"There are really no options," said one 27-year-old New Yorker with the disease, who did not want his name used because the Fabry community is so small he fears he might not get his medication.

"Recently, [Genzyme] canceled another dose for me -- the appointment was for one of two people. I don't know if they are manually picked, and I would rather not give them a reason not to pick me again. ... I don't want to be singled out as a troublemaker." His last half dose was Aug. 3.

Now, he is considering moving to France, where he has dual citizenship and can obtain the lifesaving Fabrazyme or Replagal.

"I count my blessings," he said. "Thankfully, there's a treatment option out there."

But American patients still want to know why they cannot have the same access to full doses as patients in Europe. Genzyme officials said that the European Medicine Agency has required full dosages of Fabrazyme, and the company is complying with that "guidance."

"We provide the drug to every patient in the world that needs it," countered Genzyme's Piela. "It's an extremely rare disease, and we have been treating patients in Europe, Latin America and Asia where it's been approved.

In addition to asking the FDA to stop overseas shipments of the drug, the plaintiffs filed petitions with the National Institutes of Health to allow other manufacturers to license the patent on Fabrazyme. That was denied in December.

Patients could also ask for an executive order by President Obama. "This is extraordinarily rare and used for national defense, but I think it rises to that level," said Black.

Walter said he agrees that critical action is needed.

"It's not really fair to accuse [Genzyme] of wrongdoing for a virus, but they could have planned better and built an inventory," he said. "But now, we are not confident they are doing everything they can for the Fabry community."

His last infusion was set for Aug. 16 and never arrived; as his Aug. 30 dose approaches, Walter still doesn't know if he will be able to get it.

He called Genzyme, but said, "It's been a good two weeks with no answers yet. I am about to miss my second one in a row, and I don't know what's happening. ... We are in grave need of help."

In all, 18 members of Walter's family have been affected by the X-linked genetic disorder. Men with the gene can pass it on to their daughters. Women with the gene have a 50-50 chance of passing it on to their sons or daughters.

The average age of death for an untreated male is 50, according to Walter, whose brother died at 37. He said the drug had been a godsend, but now Fabry patients feel abandoned.

"I was down to a third of a dose at one point, and now I am back to a half, but recently the shipments have been on hold completely with no expected date to return to shipping," said Walter.

Genzyme's Piela said that despite delays, August doses will be available to patients soon. "However, we do not expect to ship Fabrazyme to meet this allocation until September," he said.

"These are biologic drugs, and there is variability in production based on various factors," said Piela.

The company is in the midst of constructing a second manufacturing plant in Framingham, Mass., and when that is approved "We will be able to meet full demands," he said. "But licensing takes time."

Piela said he expects production there to be in full swing by 2012 and "significantly increase capacity and help end the supply shortage."

But that isn't soon enough for patients who say they need full dosages of the drug now.

"There are really no options," said one 27-year-old New Yorker with the disease, who did not want his name used because the Fabry community is so small he fears he might not get his medication.

"Recently, [Genzyme] canceled another dose for me -- the appointment was for one of two people. I don't know if they are manually picked, and I would rather not give them a reason not to pick me again. ... I don't want to be singled out as a troublemaker." His last half dose was Aug. 3.

Now, he is considering moving to France, where he has dual citizenship and can obtain the lifesaving Fabrazyme or Replagal.

"I count my blessings," he said. "Thankfully, there's a treatment option out there."

But American patients still want to know why they cannot have the same access to full doses as patients in Europe. Genzyme officials said that the European Medicine Agency has required full dosages of Fabrazyme, and the company is complying with that "guidance."

"We provide the drug to every patient in the world that needs it," countered Genzyme's Piela. "It's an extremely rare disease, and we have been treating patients in Europe, Latin America and Asia where it's been approved.

In addition to asking the FDA to stop overseas shipments of the drug, the plaintiffs filed petitions with the National Institutes of Health to allow other manufacturers to license the patent on Fabrazyme. That was denied in December.

Patients could also ask for an executive order by President Obama. "This is extraordinarily rare and used for national defense, but I think it rises to that level," said Black.

Walter said he agrees that critical action is needed.

"It's not really fair to accuse [Genzyme] of wrongdoing for a virus, but they could have planned better and built an inventory," he said. "But now, we are not confident they are doing everything they can for the Fabry community."

His last infusion was set for Aug. 16 and never arrived; as his Aug. 30 dose approaches, Walter still doesn't know if he will be able to get it.

He called Genzyme, but said, "It's been a good two weeks with no answers yet. I am about to miss my second one in a row, and I don't know what's happening. ... We are in grave need of help."

"I count my blessings," he said. "Thankfully, there's a treatment option out there."

But American patients still want to know why they cannot have the same access to full doses as patients in Europe. Genzyme officials said that the European Medicine Agency has required full dosages of Fabrazyme, and the company is complying with that "guidance."

"We provide the drug to every patient in the world that needs it," countered Genzyme's Piela. "It's an extremely rare disease, and we have been treating patients in Europe, Latin America and Asia where it's been approved.

In addition to asking the FDA to stop overseas shipments of the drug, the plaintiffs filed petitions with the National Institutes of Health to allow other manufacturers to license the patent on Fabrazyme. That was denied in December.

Patients could also ask for an executive order by President Obama. "This is extraordinarily rare and used for national defense, but I think it rises to that level," said Black.

Walter said he agrees that critical action is needed.

"It's not really fair to accuse [Genzyme] of wrongdoing for a virus, but they could have planned better and built an inventory," he said. "But now, we are not confident they are doing everything they can for the Fabry community."

His last infusion was set for Aug. 16 and never arrived; as his Aug. 30 dose approaches, Walter still doesn't know if he will be able to get it.

He called Genzyme, but said, "It's been a good two weeks with no answers yet. I am about to miss my second one in a row, and I don't know what's happening. ... We are in grave need of help."