Michael A. Masula, 36, lives a stone's throw from one of the researchers who developed the drug that briefly made his life so much better.
To get enough of the drug Fabrazyme, though, he would have to move from Kilbuck to Europe. That's because Boston-based Genzyme Corp., the maker of Fabrazyme, developed with local expertise and federal funds, is strictly rationing the drug in the United States while European medical regulators demand that patients there get their regular treatment regimen.
"Why is it OK for Americans to take a half or a third [of a] dose when the Europeans have a different standard?" asked Erin Masula, Mr. Masula's wife, who has agonized as her husband's symptoms from Fabry's disease -- gastrointestinal turmoil, stabbing pain and palpitations in his heart, aching and swelling of the hands and feet -- returned after Genzyme cut his dose in half.
For the estimated 2,000 Americans with Fabry's disease, news that some overseas patients don't face the same strict rationing that they do here has capped two years of frustration.
Before 2003, most depended on dialysis and kidney transplants to keep them alive past age 50. From 2003 to 2009, they had Fabrazyme, which stopped the deterioration in their vital organs caused by Fabry's disease, a genetic inability to clear certain waste molecules from cells.
Then, in 2009, a virus infected the biotech plant that creates Fabrazyme. Around the same time, federal regulators, armed with information from an internal whistle-blower, slapped Genzyme with a fine and took oversight of drug production.
Genzyme expects "to return patients to normal dosing within the fourth quarter of this year, and we continue to make progress toward meeting this goal," said a company spokeswoman, in a written response to questions.
None of its production problems stopped company executives from completing the sale of the firm to a European drug giant, resulting in eight- and nine-figure payouts to top executives. Patients are suing and hoping federal agencies will come to their aid.
John Barranger of Ben Avon Heights -- next door to Kilbuck -- has been a consultant to Genzyme since the early 1980s, when his research for the National Institutes of Health contributed to the development of Fabrazyme and other drugs. In February, he filed a writ in Allegheny County Court of Common Pleas preserving his right to sue the company.
"When it came time that Genzyme was really going to be acquired [by French pharmaceutical titan Sanofi-aventis], I was offended," Dr. Barranger explained last week. A company that could have been "the jewel of biotechnology," dedicating itself to saving the lives of thousands worldwide, became more interested in "the idea that one needed to be 'big pharma.' "
Genzyme was a few years old, with a few dozen employees, when Dr. Barranger agreed to provide it with technology he'd been developing at NIH since 1976. His team studied lysosomes, tiny incinerators within cells that break down waste molecules. If the body lacks certain specialized enzymes, the waste products build up in the cells, causing debilitating conditions like Fabry's disease and Gaucher's disease.
His team, and a competing unit led by Robert J. Desnick of Mount Sinai School of Medicine, figured out how to synthesize the enzymes. They are now made in 4,000-liter vats of Chinese hamster ovary cells, infused with a human gene, that churn out life-saving Fabrazyme and, for Gaucher's patients, Cerezyme.
Such medicines are known as "orphan drugs," because the market for them is too narrow to support the costs of development. Development often requires federal funding, and the ultimate price tag for the treatment can be staggering.
The NIH granted $4.1 million toward Fabrazyme's development from 1984 through 1999. A year's worth of treatment costs upward of $160,000. Mr. Masula's annual hospital bill for Fabrazyme and related treatment tops $400,000.
Dr. Barranger consulted for Genzyme part time while at the NIH and then while serving as a professor at the University of Pittsburgh from 1990 through 2004. He helped Genzyme full time for several years after that. He loved what he and the company were able to achieve.
"The children I treated when they were young are adults who have no mark of the disease," Dr. Barranger said.
Mr. Masula said he "was feeling like an 18-year-old who could conquer the world" after he started taking Fabrazyme at age 33. His pain eased, he didn't need to be constantly aware of the location of the nearest bathroom and he began sweating for the first time in his life.
The company was happy, too.
Fabrazyme "delivered double-digit growth in 2008 in a market that is competitive outside the United States," Genzyme boasted in an annual report that portrayed enzyme replacement drugs as stars of its portfolio. Fabrazyme competes overseas with Replagal, which has not been approved for general use domestically. In 2008, Genzyme brought in $4.6 billion in revenue and made a profit of $420 million.
Dr. Barranger said he was promised a small percentage of the gross from his inventions and initially took no action when he didn't get the compensation he expected. Then Genzyme executives negotiated a $20 billion sale of the firm to Sanofi-aventis.
Filings with the Securities and Exchange Commission show Genzyme executives getting eight-figure paydays from the sale. CEO Henri Termeer is getting $146 million and, potentially, another $63 million in contingency payments, according to the filings.
"You can't be walking away with bags of $150 million, like Henri Termeer did, and not pay for the technology, as you promised," Dr. Barranger said.
He has not yet filed a complaint detailing his allegations and demands. He continues to treat Fabry's patients, but he's frustrated that his patients can't get their recommended doses of Fabrazyme and that only a handful of new patients can get the drug.
Genzyme should have stockpiled Fabrazyme, he said. It should have built a backup production line. Instead, the company was "making a lot of money for their shareholders."
"They took far too many profits," he said, "out of the cures of these diseases."
Alan R. Boisvert saw the quest for profit manifest itself as an unwillingness to spend money.
As a lead maintenance technician at Genzyme in 2008, Mr. Boisvert refused to sign off on inspections that he believed never happened, according to a lawsuit he filed in the Trial Court of Massachusetts.
Instead, he started looking deeper into conditions in and around the "clean rooms" where cells churned out Fabrazyme and Cerezyme, he said.
Among his findings: "There were dead bugs, like a carpet of them, up [in the ceiling], right above the clean rooms," Mr. Boisvert said in an interview. Dust was entering the clean room. Equipment meant to supply pure water was rusting. Mold grew.
Starting in mid-2008, he took his concerns up the chain of command, sending a slew of emails and getting meetings, eventually reaching Mr. Termeer. At every stage, he was told the problems wouldn't hurt anyone.
"Wait a minute," he said in the interview. "We've got rust in the medicine, we've got bugs, we've got all of these problems. And you're telling me there's no problem for the patients.
"I can't be that guy who signs off and then someone uses that medicine."
He said minor repairs were made, but not the complete revamp that was warranted.
On Aug. 20, 2009, he contacted the Food and Drug Administration. On Aug. 27, according to his complaint, Genzyme fired him.
Currently unemployed, Mr. Boisvert is pursuing his whistle-blower lawsuit pro se, since he has been unable to find an attorney to take the case. He faces an Aug. 9 hearing on Genzyme's motion to dismiss.
When Mr. Boisvert approached the FDA, it was already in the midst of a review of Genzyme's production lines. An October 2008 inspection found inadequate maintenance, poor air flow through the facility and other technical problems.
In early 2009, a hard-to-eradicate virus infiltrated the production lines, crippling the hamster ovary cells and forcing a slowdown. Because there was no back-up production line and very little inventory, the company began rationing Cerezyme and Fabrazyme, giving patients half, or sometimes one-third, of their usual dose. It has frequently suggested that a return to full doses is around the corner and recently announced that a new plant could be open at year's end.
"Adequate dosing matters," Dr. Barranger said. "If you don't take enough, you get sick."
For Mr. Masula, a half-dose has meant a return to constant bathroom trips, hyper-sensitive hands and feet and also chest pain that has made him think he was having a heart attack. He and his wife of two years have put off deciding whether to have kids.
"I don't know what's going to happen on what day," said Mr. Masula, who has continued his career selling steel buildings.
"Lately," Mrs. Masula said, "there have been a lot more bad days."
The FDA inspected Genzyme's plant again in October and November 2009, and this time it detected metal, fiber, rubber and glass contamination in the drugs.
In May 2010, the agency forced Genzyme into a consent degree under which it paid more than $175 million in profits, exacted a promise to bring its production lines back into compliance and took over supervision of drug production.
Dr. Barranger said the FDA's action was driven less by contamination than by the company's failure to have a plan in place to deal with a production slowdown. "The real reason why the FDA came down that hard on Genzyme is that they did not provide that level of consideration for the patients."
From the beginning, the European Medicines Agency was skeptical of the idea of rationing Fabrazyme.
"Patients who demonstrate a deterioration of disease should reinitiate the original treatment with Fabrazyme," the EMA wrote in a September 2009 press release about the shortage. Genzyme echoed that language in advisories to European physicians.
In October 2010, the EMA took a harder line after it noted "an increase in reported adverse events" in patients on reduced doses of Fabrazyme. "At first, most of the events were pain-related, soon followed by reports of events affecting the heart, the central nervous system and the kidneys," the agency wrote in a press release. It recommended "that physicians switch back to prescribing the full dose of Fabrazyme" or switch to Replagal.
"Europeans get a full dosage. Americans don't," said attorney C. Allen Black of McCandless, who represents Fabry's patients. "It's absolutely bizarre that Americans should essentially have no choice and be kept on a low dose, while the Europeans who have a choice [of Replagal] should be able to get a full dose."
He said he believes that Genzyme is treating Europe differently because it doesn't want to lose customers there to Replagal. To the contrary, wrote a Genzyme spokeswoman, the company has "worked with local physician experts to switch many [European] patients to other treatment," while others have returned to full doses of Fabrazyme.
Late last year, patients represented by Mr. Black asked the NIH to authorize other manufacturers to make Fabrazyme, under the agency's never-used power to "march in" on medical patents developed with its funds if the inventions are not being used.
Initially rebuffed, the patients asked NIH for reconsideration this year when they learned European patients were getting back their regular doses.
Mr. Black and attorney Matthew L. Kurzweg also filed a federal lawsuit against Genzyme and Mount Sinai in Pittsburgh in March. It was transferred at Genzyme's request to U.S. District Court in Boston in April. The 20 plaintiffs include Mr. and Mrs. Masula.
Genzyme has responded in court filings that the plaintiffs haven't demonstrated that they've suffered any injury or made a legally viable case.
Though their complaint demands money, plaintiffs have said it's really about pressuring the company to restore full doses -- before someone dies.
"Right now this is a product liability action," Mr. Black said. "We don't want it to be a wrongful death. We want the drug."
Rich Lord: firstname.lastname@example.org or 412-263-1542