WASHINGTON _ A panel of experts convened by the NationalInstitutes of Health (NIH) concluded that while Genzyme Corp.'senzyme therapy for Gaucher's disease is an unmitigated success, thecost of treatment remains a serious problem. They said thatgovernment-sponsored clinical trials to determine the "lowesteffective initial and maintenance doses" of Ceredase (or the secondgeneration recombinant product, Cerezyme) should be a researchpriority.
In addition, the panel recommended a study of enzyme therapy'spotential as a prophylactic treatment in asymptomatic, enzyme-deficient patients, a clinical indication that could enlarge the potentialmarkets for Genzyme's drug.
Gaucher's disease, a rare inherited enzyme deficiency that afflictsbetween 10,000 to 20,000 Americans, is a potentially lethal disorder.A genetic defect in the enzyme glucocerebrosidase causes anaccumulation of lipids within intracellular structures calledlysosomes, debilitating many patients. Anemia, bone damage, andenlarged livers and spleens are common and some Gaucher'ssufferers sustain severe central nervous system damage.
Genzyme, of Cambridge, Mass. manufactures and markets Ceredaseand Cerezyme for type 1 Gaucher's disease in adults, by far the mostcommon form (type 2 afflicts infants and type 3, juveniles). Bothdrugs are expensive to produce, even though Cerezyme is arecombinant form of the first generation product, Ceredase, whichmust be painstakingly extracted from tons of human placentas.
According to company estimates, only about 2,500 patients in theU.S. are deemed ill enough to need Ceredase or Cerezyme. One yearof therapy can range anywhere from $100,000 to $400,000 perpatient, but the average cost is closer to $145,000.
Controversy over the high price of Ceredase has plagued Genzymesince the drug first hit the market in 1991. Part of the uproar was dueto the fact that NIH scientists initially discovered and tested enzymereplacement therapy while Genzyme later developed it and brought itto market.
The company even took the unusual step of opening its books lastyear during the health care reform battle over drug prices. Thatexercise revealed that Genzyme's pretax margins on Ceredase are 31percent, lower than the pharmaceutical industry's estimated averagepretax margin of 50-plus percent. Nevertheless, the company'saverage margin per patient still chalks up to $45,000 a year.
In an attempt to lower the extraordinary costs to patients and insurers,physicians have experimented with using lower doses of Ceredase.One study published in The New England Journal of Medicine in1992 showed that by changing the schedule of recommended doses,some patients do as well on one-fourth the recommended amount ofdrug.
As a result of that study and others, debate about the correct dosage,methods and frequency of administration of enzyme therapy havebeen simmering for years. The NIH panel, composed of specialistsand generalists from the medical and other related scientificdisciplines, as well as a public representative, was given the task ofevaluating the current state of Gaucher's disease therapy, diagnosisand screening efforts.
The panel concluded that widespread genetic screening, either todetect presymptomatic Gaucher's disease patients or carriers of thedisease, is "not appropriate at this time" because the medical value ofidentifying these individuals has not been established. But thehypothesis that enzyme therapy used prophylactically might benefitasymptomatic patients should be tested in clinical trials.
A 20-page "technology assessment statement" written by the panelacknowledged that both high and low dose regimens ofCeredase/Cerezyme have shown efficacy in clinical trials. But thedebate over dosage has been complicated by "the failure to comparedata in an adequate fashion and the diversity of protocols."Apparently, patients vary considerably and unpredictably in theirresponse to therapy, although many seem to benefit from low doseregimens.
"Answering the many questions concerning the management ofGaucher's disease will require a cooperative effort of considerablescale," the panel's report stated. "For this cooperative to have itsintended impact, it will be important that the organizer of this effortbe free of real or perceived bias. The NIH should take the initiativeand foster the establishment of a cooperative group of investigatorsinvolved in the diagnosis and treatment of patients with Gaucher'sdisease."
Further, the panel recommended the establishment of a nationwideclinical data base "independent of any corporate entity" and theinitiation of nationwide controlled clinical trials "free of influencefrom any commercial entity."
Genzyme has long argued that economies of scale (i.e., producinglarger amounts of drug for a larger patient population is cheaper)impact the high price tag of its drugs. NIH panelists agreed. "As aprototype for all rare disease, the plight of the patients withGaucher's disease raises difficult financial and ethical issues, whichwe as a society must address," the panel wrote. n
-- Lisa Piercey Washington Editor
(c) 1997 American Health Consultants. All rights reserved.