Budget Impact Analysis of Eliglustat for the Treatment of Gaucher Disease Type 1 in the United States.

BACKGROUND: Gaucher disease type 1 (GD1) is a rare, genetic, lysosomal storage disease with no cure. Current treatment options include intravenous (IV) enzyme replacement therapy ([ERT]; imiglucerase, velaglucerase alfa, or taliglucerase alfa) or oral substrate reduction therapy ([SRT]; eliglustat or miglustat). The cost to U.S. payers of an IV-administered drug can vary depending on the site of care (i.e., home, outpatient clinic, or hospital setting). Treatment with oral eliglustat may present an opportunity for cost savings. OBJECTIVE: To evaluate the budget impact from a U.S. payer perspective associated with transitioning patients receiving ERTs to the oral SRT eliglustat for the treatment of adults with GD1. METHODS: A budget impact model estimated the change in pharmaceutical and administration costs resulting from increasing the market share of eliglustat from 12% (current) to 44% (new). The market share for eliglustat was drawn equally from existing shares of imiglucerase (40%) and velaglucerase alfa (40%) and assumed to be static over the analysis period. ERT costs were adjusted to account for site of care-based markup and the proportion of patients receiving infusions in each site of care (home, infusion center, or hospital outpatient). Annual ERT costs were calculated assuming a biweekly dose of 47.4 U per kg, a 72-kg patient weight, and 24 infusions per year. The effect of key variables was tested in the sensitivity analyses. All costs are expressed in 2017 U.S. dollars. RESULTS: In a new plan with 5 million members and 25 GD1 treated patients, increased use of eliglustat resulted in an annual savings of $1,526,710 and a total savings of $4,580,130 (13.6%) over 3 years. The corresponding annual per member per month savings was $0.025. This is further illustrated in the sensitivity and scenario analyses where the use of eliglustat was cost saving in all cases. Shifting more patients receiving ERT in the hospital outpatient setting to eliglustat resulted in increased savings. CONCLUSIONS: Based on these analyses, increased use of eliglustat resulted in meaningful cost savings to a payer's overall budget. Cost savings are highest among patients switching from ERT administered in a hospital outpatient setting. The results suggest that cost savings are also likely achievable from initiating patients on oral eliglustat instead of infusion-based therapy from the outset of treatment. DISCLOSURES: This study was sponsored by Sanofi Genzyme. Evidera received funding from Sanofi Genzyme to conduct this study and prepare the manuscript. The sponsor collaborated on the study design, analysis, interpretation of results, and writing of the manuscript. Nalysnyk is an employee of and shareholder in Sanofi Genzyme. Ward, Cele, and Uyei are employees of Evidera, which provides consulting and other research services to biopharmaceutical companies. Sugarman was also an Evidera employee when the study was being conducted and the manuscript written. This study was presented as a poster at the Academy of Managed Care Pharmacy Nexus 2016, October 3-6, 2016; National City, MD, and at the International Society for Pharmacoeconomics and Outcomes Research, 22nd Annual International Meeting; May 20-24, 2017; Boston, MA.

Alglucerase. A pharmacoeconomic appraisal of its use in the treatment of Gaucher's disease.

Alglucerase is a modified form of human placental glucocerebrosidase used as enzyme replacement therapy for patients with Gaucher's disease, in whom functional glucocerebrosidase is deficient. Alglucerase has provided a breakthrough in treatment for patients with this relatively rare disease. With alglucerase infusions typical disease manifestations are ameliorated or normalised: hepatosplenomegaly is reduced, haematological parameters improve, and patients experience an increased quality of life usually within 4 to 6 months of treatment. Parameters of bone disease also respond, but generally over a longer period of treatment. Alglucerase is well tolerated by children and adults, with few adverse effects reported. Seroconversion occurs in approximately 15% of patients on high-dose therapy, but does not appear to affect the efficacy of treatment. Several dosage regimens have been used to deliver alglucerase, and the comparative benefits of these remain controversial. High-dose regimens of 60 IU/kg bodyweight administered every 2 weeks are clearly effective; however, smaller dosages given more frequently are also effective and incur a greatly reduced acquisition cost. Patient responses are variable, and the dosage regimen should be tailored to individual needs. Dosage regimens may be considerably reduced for the maintenance phase of treatment, but clinical experience is as yet insufficient to establish the minimum dosages required in the long term. Acquisition cost of alglucerase is $US3.70 per unit (1994 US dollars); thus, a dosage regimen of 60 IU/kg bodyweight administered every 2 weeks for a patient weighing 70kg costs $US404,040 per year. The minimal costs per quality-adjusted life year saved (QALY) have been estimated for 3 dosage regimens over a 10-year period. Cost per QALY was $US147,000 for 60 IU/kg bodyweight administered every 2 weeks, $US75,000 for 30 IU/kg every 2 weeks, and $US49,000 for 2.3 IU/kg administered 3 times per week. These costs were calculated assuming immediate death with no treatment, which suggests that the actual costs per QALY for most patients with type 1 or 3 disease are likely to be much higher. Drug administration costs may become a significant part of the cost during maintenance therapy; in addition, possible cost savings due to increased patient productivity and reduced palliative treatments remain unresolved. Although some patients may obtain increased benefit from high-dosage regimens, the very high cost may preclude general use of these regimens. Healthcare resources consumed by alglucerase therapy represent a large opportunity cost for other therapeutic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Imiglucerase in the treatment of Gaucher disease: a history and perspective.

The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ultra-orphan disorder: Gaucher disease.

Stakeholder involvement in expensive drug recommendation decisions: an international perspective.

OBJECTIVES: To describe stakeholder involvement in the priority setting and appeals processes across five drug reimbursement recommendation committees. METHODS: We conducted qualitative case studies of how five independent drug advisory committees from Canada, Israel, England and Wales, Australia, and the USA made funding decisions for six expensive drugs. Interviews with 48 informants were conducted with committee members, patient groups, and industry representatives. RESULTS: Different stakeholders were allowed, in varying degrees, to participate in the formal mechanisms for revisions and appeals of decisions. Participants identified a number of stakeholder groups who were already involved in the process, as well as stakeholders whom they believed should be included in the decision-making process. CONCLUSIONS: A central component of a legitimate and fair priority setting process is to make priority setting explicit and to involve both pertinent values and stakeholders in decision-making. Study participants believed that the involvement of multiple stakeholder groups within the deliberative and appeals/revisions processes would contribute to a fair and legitimate drug reimbursement process.

A plant-derived recombinant human glucocerebrosidase enzyme--a preclinical and phase I investigation.

UNLABELLED: Gaucher disease is a progressive lysosomal storage disorder caused by the deficiency of glucocerebrosidase leading to the dysfunction in multiple organ systems. Intravenous enzyme replacement is the accepted standard of treatment. In the current report, we evaluate the safety and pharmacokinetics of a novel human recombinant glucocerebrosidase enzyme expressed in transformed plant cells (prGCD), administered to primates and human subjects. Short term (28 days) and long term (9 months) repeated injections with a standard dose of 60 Units/kg and a high dose of 300 Units/kg were administered to monkeys (n = 4/sex/dose). Neither clinical drug-related adverse effects nor neutralizing antibodies were detected in the animals. In a phase I clinical trial, six healthy volunteers were treated by intravenous infusions with escalating single doses of prGCD. Doses of up to 60 Units/kg were administered at weekly intervals. prGCD infusions were very well tolerated. Anti-prGCD antibodies were not detected. The pharmacokinetic profile of the prGCD revealed a prolonged half-life compared to imiglucerase, the commercial enzyme that is manufactured in a costly mammalian cell system. These studies demonstrate the safety and lack of immunogenicity of prGCD. Following these encouraging results, a pivotal phase III clinical trial for prGCD was FDA approved and is currently ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT00258778.

Lysosomal storage diseases: natural history and ethical and economic aspects.

Potential treatment for lysosomal diseases now includes enzyme replacement therapy, substrate reduction therapy, and chaperone therapy. The first two of these have been implemented commercially, and the spectrum of diseases that are now treatable has expanded from Gaucher disease to include several other disorders. Treatment of these diseases is extremely costly. We explore some of the reasons for the high cost and discuss how, by proper selection of patients and appropriate dosing, the economic burden on society of treating these disease may be ameliorated, at least in part. However, the cost of treating rare diseases is a growing problem that society needs to address.

Gaucher disease, enzyme replacement therapy, and the Patient Assistance Program.

Gaucher disease is the most common lysosomal storage disorder characterized by a missing enzyme, glucocerebrosidase. Enzyme replacement therapy has been available in the form of Ceredase (Genzyme Corporation, Cambridge, Massachusetts) (alglucerase injection) since 1991, and in the form Cerezyme (Genzyme Corporation, Cambridge, Massachusetts) (imiglucerase for injection) since 1994. Because of the high cost associated with enzyme replacement therapy, the Genzyme Corporation, manufacturers of Ceredase and Cerezyme, developed the Patient Assistance Program. The program assisted those patients who chose to use it with the facilitation of coverage approvals from their insurance carriers. The program has become a comprehensive case management service made up of nurses and social workers who work with patients on many issues from access to coverage. Case managers also provide support to providers who are transitioning patients to home therapy. Home health agencies can benefit from the information and assistance offered by this program as well as other resources throughout Genzyme and the Gaucher community.

Glucocerebrosidase for treatment of Gaucher's disease: first German long-term results.

Until recently, there was no specific therapy available for patients with Gaucher's disease. Since April 1991 a highly purified human placental preparation of glucocerebrosidase (Ceredase, Genzyme) has been available for clinical studies in Germany. Sequential deglycosylation of the native enzyme yields a mannose-terminated preparation that may preferentially bind to the plasma membrane of macrophages. The present report analyzes the first German (and European) long-term results with glucocerebrosidase therapy in five patients with type I Gaucher's disease (four women and one man, aged 29-40 years). All patients suffered from excessive enlargement of the liver and spleen with subsequent pancytopenia and from skeletal complications. Multiple pathological fractures had already occurred in three of the five patients, requiring several surgical procedures. Fatigue and asthenia were present in all patients. The initial dose of glucocerebrosidase was chosen according to the severity of complications in the individual patient (20-50 U/kg given i.v. every 2nd week) and was performed in the five patients for 12-18 months. After a few weeks all patients reported that fatigue and asthenia were markedly reduced. After 12 months, blood counts of erythrocytes, leukocytes and platelets had completely normalized in all but one of the patients. After 4-6 months a significant reduction in the sizes of liver and spleen could be observed in all patients. No further fractures occurred during treatment. Significant side-effects of glucocerebrosidase treatment did not occur. The new glucocerebrosidase preparation offers the first effective drug therapy for patients with Gaucher's disease. Although the treatment proved effective and harmless, it is, at least initially, very expensive.(ABSTRACT TRUNCATED AT 250 WORDS)

A less costly regimen of alglucerase to treat Gaucher's disease.

BACKGROUND: Alglucerase (Ceredase) provides effective enzyme-replacement treatment for patients with Gaucher's disease, but at the usually recommended dose of 60 U per kilogram of body weight every two weeks (130 U per kilogram per month), it costs $382,200 per year for a 70-kg patient. Theoretical considerations suggest that more frequent administration would be more efficient. METHODS: Fourteen patients with type 1 Gaucher's disease that was moderately severe to severe were given 30 U of alglucerase per kilogram per month, in divided doses given either daily or three times weekly, or 120 U given three times weekly. The effect of the treatment on the size of the liver and spleen and on blood counts was compared with published data on patients who received a total dose four to five times as large as the lower dose we used and who received treatment every two weeks. RESULTS: The response to 30 U of alglucerase per kilogram per month, fractionated into three or seven doses weekly, was approximately the same as that reported after the administration every two weeks of a dose four or five times as large, given in the large infusions usually recommended. A fourfold increase in the dose given three times weekly, from 2.3 to 9.2 U per kilogram, did not substantially increase the rate of improvement. CONCLUSIONS: The treatment of Gaucher's disease with smaller total doses of alglucerase given more frequently yields satisfactory results. A dose of 2.3 U per kilogram three times weekly yields major financial benefits with no sacrifice of therapeutic effect. Even taking into account the increased ancillary costs of more frequent administration, this method of administering alglucerase reduces the annual cost of the drug for a 70-kg patient to about $100,000.

Creating the costliest orphan. The Orphan Drug Act in the development of Ceredase.

The FDA recently approved Ceredase, a new treatment for Gaucher's disease, under the provisions of the Orphan Drug Act. Ceredase is unusually expensive, but there are no satisfactory alternative therapies. It appears likely that Ceredase would not have become available without the protection of the Orphan Drug Act, but its expense and the lack of information about its long-term effects on health raise questions about whether the ODA provides appropriate incentives to develop cost-effective technologies.