The Massachusetts biotech company Genzyme showed everybody else the way to make money by developing ultra-high-priced drugs for people with rare diseases. But lately it’s discovered the downside of that strategy.
And boy, is it a big one.
In the year since Genzyme discovered viral contamination in equipment used to produce the $300,000-a-year drug Fabrazyme, and then foreign particles like bits of stainless steel in vials of the drug, the company has been fined $175 million by the Food and Drug Administration and become a takeover target.
Fabrazyme replaces a missing enzyme in patients who have a genetic disease that can lead to an early death. But Genzyme's manufacturing woes mean the medicine is in short supply — less than a third of the needed amount is available.
Now patients who depend on Fabrazyme are asking Health and Human Services Secretary Kathleen Sebelius to exercise "march-in rights" under a 1980 law to abrogate Genzyme’s patent on the drug, allowing another company to fill the demand.
Such petitions have been filed several times – never successfully. But this is the first time patients have made the case, alleging that a patent-holder isn’t satisfying their needs.
"They have not taken proper care of those patients that have these rare diseases," says Joseph Carik, a 53-year-old Fabrazyme patient in Las Vegas who filed the petition yesterday along with his cousin Anita Hochendoner and her daughter Anita Bova.
All three have Fabry disease, a rare genetic disorder that interferes with fat metabolism. And, all told, 22 members of Carik's family have Fabry disease.
Fats build up in virtually every tissue of the body, leading to premature death from heart and kidney failure. Along the way, though, patients suffer pain in the arms and legs, severe intestinal problems, profound fatigue and other maladies.
There may be as many as 50,000 people with the disorder, but only about 1,500 depend on Fabrazyme, which was approved in 2001. The rest are presumably undiagnosed or misdiagnosed.
Carik and other Fabrazyme patients are currently able to get only 30 percent of the needed dose. That’s because Fabrazyme production is only 30 percent of normal. Genzyme says it hopes to begin increasing supplies by late this year, but it’s making no promises about when stocks will be in full supply.
"We sympathize with the challenges patients are facing," Genzyme said in a statement yesterday, "and we share a common goal of restoring reliable supplies of product for all patients."
The company said it's making "excellent progress" on a new manufacturing plant "which is on track for approval next year." Genzyme declined to make anyone available for an interview.
But a string of broken promises has alienated many patients who were once loyal to the company and led to this week's petition.
"Since the shortage in 2009, three to six months turned into six to nine, nine to 12, and now we’re (talking about) late 2011," Carik says. "I would like to have a backup plan, for myself, for my famly, and for those in the Fabry community. I do not know of a backup plan"
Patients are especially anguished because one backup plan has evaporated – while they waited for Genzyme to get past rationing of Fabrazyme.
The British drugmaker Shire had offered to supply its Fabry enzyme-replacement drug, Replegal, free of charge to U.S. patients under an emergency-use provision. Shire applied to the FDA for market approval of Replegal earlier this year.
However, a Shire spokeswoman says only about 100 Fabry patients in this country have accessed Repligal so far. And this summer – just around the time Genzyme announced another delay in increasing Fabrazyme supplies – Shire said it could no longer provide Replegal to new patients.
Allen Black, a Pittsburgh patent attorney who’s representing the Fabry disease petitioners on a pro-bono basis, says many Fabrazyme patients were holding back from accepting Shire’s earlier offer.
"They’ve been told by Genzyme that drug was on its way, that the problem is going to be fixed soon, there’s nothing to worry about," Black says."They probably wish they had applied (to Shire) for treatment. They were led to believe they would be OK, essentially."
Carik especially regrets not urging his cousin's daughter Anita Bova to take Shire up on its offer. She’s only in her late 40s, and since Fabrazyme has been rationed, she has developed heart failure, Carik says.
Carik and Allen acknowledge they face an uphill battle in getting HHS, or the National Institutes of Health, which funded initial studies that led to Fabrazyme, to exercise their march-in rights. It’s never happened before.
But even if their petition is granted, it’s not at all clear what practical effect it would have. No other company is waiting in the wings to take advantage of an opportunity to make Fabrazyme, and even if there were, it would take time to gear up to make it and get past various regulatory hurdles.
And as Genzyme’s experience amply demonstrates, Fabrazyme is not a snap to make.
Still, the petitioners hope they will bring attention to the need for a back-up supply for life-saving drugs – either stand-by capacity from more than one supplier, or inventory requirements to address manufacturing glitches.
Meanwhile, frustrations are running high in the small community of Fabry disease patients and caregivers – and anxiety may be mounting among other sufferers of "orphan" diseases who depend on the biotech industry.
"We’re been promoting awareness of Fabry disease for several years because we think it’s potentially life-saving to get on therapy," says Dr. Robert Hopkin of Cincinnati Children’s Hospital Medical Center. "And now we have patients who want treatment, who qualify for treatment and there's just no medicine available."