Medication Policy Manual. Topic: Lumizyme, alglucosidase alfa Date of Origin: February 17, 2015

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1 Medication Policy Manual Policy No: dru392 Topic: Lumizyme, alglucosidase alfa Date of Origin: February 17, 2015 Committee Approval Date: March 13, 2015 Next Review Date: March 2016 Effective Date: July 1, 2015 IMPORTANT REMINDER This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status. Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care. Description Alglucosidase alfa (Lumizyme) is an enzyme replacement therapy (ERT) indicated for the treatment of Pompe disease (a.k.a. glycogen storage disease type II), an inherited disorder characterized by the absence or marked deficiency of an enzyme [acid alpha glucosidase (GAA)] responsible for the breakdown of glycogen in muscle cells throughout the body. Accumulation of glycogen in muscle cells can lead to movement and breathing difficulties. Pompe disease can present as infantile or late-onset form dru392.0 Page 1 of 6

2 Policy/Criteria I. Most contracts require prior authorization approval of alglucosidase alfa prior to coverage. Alglucosidase alfa may be considered medically necessary in patients with Pompe disease when criteria A, B, and C below are met. A. Alternative Site of Care - for Washington, Oregon, and Idaho commercial, fully insured members only (does not apply to Medicare) Alglucosidase alfa is administered in a non-hospital outpatient setting (also referred to as an alternative site of care ; such as a provider s office, an infusion center, or home infusion), unless both of the following criteria 1 and 2 below are met: 1. All non-hospital outpatient settings are greater than 10 miles further from the member s home than the hospital outpatient setting. AND 2. The member s home is not eligible for home infusion services (such as home is not within the service area or is deemed unsuitable for care by the home infusion provider). NOTE: Alternative Site of Care criteria will be waived for payment of the first dose, to allow for adequate transition time to arrange for a non-hospital outpatient setting for the infusion. AND B. A diagnosis of Pompe disease confirmed by biochemical assay of acid alphaglucosidase (GAA) enzyme activity in dried blood spots that is less than 20% of normal activity AND one of the following: 1. Genotyping revealing a disease-causing mutation in the GAA gene. OR 2. Elevated lysosomal glycogen levels in muscle cells. AND C. One or more clinical signs or symptoms of Pompe disease are present such as hypotonia, cardiac hypertrophy, muscle weakness of the trunk or lower limbs, or respiratory insufficiency. II. Administration, Quantity Limitations, and Authorization Period A. OmedaRx does not consider alglucosidase alfa to be a self-administered medication. B. When prior authorization is approved, alglucosidase alfa may be authorized for up to 26 infusions per year based on a total dose of less than or equivalent to 20mg/kg every 2 weeks, in a non-hospital outpatient setting, unless waived per criteria I.A. above dru392.0 Page 2 of 6

3 NOTE: Alternative Site of Care criteria will be waived for payment of the first dose, to allow for adequate transition time to arrange for a non-hospital outpatient setting for the infusion C. Authorization shall be reviewed at least annually to confirm that that the medication is effective. Documentation by chart notes of disease stability or improvement in symptoms must be provided. III. Alglucosidase alfa is considered not medically necessary when administered in doses exceeding 20mg/kg every 2 weeks. IV. For Washington, Oregon, and Idaho commercial, fully insured members only (does not apply to Medicare) Alglucosidase alfa is considered not medically necessary when administered in a hospital outpatient setting, when an alternative site of care (non-hospital outpatient setting) is a treatment option (see Section I: Alternative Site of Care). Position Statement - There is moderate certainty in the evidence that alglucosidase alfa (Lumizyme) results in improvement in lung and muscle function, and survival in patients with Pompe disease. - Diagnosis of Pompe disease is often difficult as it can clinically resemble a myriad of other neuromuscular disorders. Pompe disease is confirmed via genetic sequencing through biochemical and genetic testing. Although measurement of GAA enzyme activity is a non-invasive method of screening for Pompe disease, additional testing is necessary for final confirmation. [1] - In addition to ERT, other treatment options for late-onset Pompe disease include diet modification (high protein, low carbohydrate), exercise, and supportive care (e.g. mechanical ventilation for respiratory failure). [2] - The population for which the approval of alglucosidase alfa was approved on had clinical manifestations of Pompe disease [e.g. hypotonia, cardiac hypertrophy, muscle weakness of lower extremities, or low predicted force vital capacity (FVC)]. There is currently no high quality evidence indicating that treating asymptomatic patients with Pompe disease leads to a reduced risk of long term clinical outcomes such as mortality. - Alglucosidase alfa is administered intravenously in doses of up to 20mg/kg every 2 weeks. [3] Guidelines recommend evaluating patients annually to assess disease stability or improvement. Disease stability can be defined as a lower rate of decline in end-organ damage (lung and cardiac disease). - Studies have not demonstrated superior clinical benefit in patients receiving of 40 mg/kg every 2 weeks dosing versus those who received 20mg/kg every 2 weeks. [3] dru392.0 Page 3 of 6

4 - New technologies and pharmaceuticals allow therapeutic services, such as infusion therapy, to be administered safely, effectively, and much less costly outside of the hospital outpatient setting. Alternative sites of care (such as doctor s offices, infusion centers, and home infusion) are well-established, accepted by physicians, and reduce the overall cost of care. Clinical Efficacy - There is moderate certainty in the evidence for the use of alglucosidase alfa in the treatment of both infantile and late-onset Pompe disease, based on three low-confidence studies in patients with infantile-onset Pompe disease and one high-quality systematic review of studies evaluating alglucosidase alfa in patients with late-onset Pompe disease. - Three open-label controlled studies evaluated alglucosidase alfa in 57 treatment naïve patients aged 0.2 months to 3.5 years with infantile-onset Pompe disease treated for 52 to 104 weeks. [3] * Primary outcomes assessed were death and the need for invasive ventilator support. * All studies demonstrated a significant survival benefit, with 76% to 88% of subjects alive at the time of the primary efficacy analysis. Historical controls were used to compare relative efficacy of alglucosidase alfa to no treatment in one study. Two percent of historical controls were alive at the same point in time as the primary efficacy endpoint (18 months). In all the trials, a minority of patients required invasive ventilator support, which ranged from 0% to 17% of subjects treated with alglucosidase alfa. * One of the pivotal trials evaluated 20mg/kg and 40mg/kg dosing of alglucosidase alfa in patients with infantile-onset Pompe disease. No difference in efficacy (i.e. survival) was noted for either dose. * The precision of the study results is uncertain due to the absence of a control group in two of the studies, and the use of a historical control group in one of the studies. - One high quality systematic review of 21 studies evaluated the use of alglucosidase alfa in a total of 368 patients with late-onset Pompe disease. [4] * The top four outcomes with the most data included reduction in creatinine kinase levels (n=138), increased motor performance as measured by the six minute walk test (n=122), improved respiratory status as measured by forced vital capacity (n=124), and the reduction in need for ventilator support (n=66). * Although quality of life was assessed in some trials, no assessment tools have been designed to specifically measure the impact of clinical improvements on quality of life in patients with late-onset Pompe disease. * Results for all four endpoints demonstrated improvement or stability in a majority of patients receiving alglucosidase alfa. The percent of subjects showing improvement or stability in creatinine kinase, motor performance, respiratory status and duration of ventilator support were 81%, 86%, 65.3%, and 95.5% respectively. dru392.0 Page 4 of 6

5 * The studies included in the systematic review were of low quality as study populations were small (n<90), most studies evaluated surrogate endpoints, and retrospective studies were included in the systematic review (case reports, observational studies, and statistical analyses) undermining the certainty in the evidence of clinical benefit. - A guideline based on the available evidence and consensus recommendations of specialists experienced in the treatment of late-onset Pompe disease recommend initiating treatment with ERT at the onset of symptoms and to re-evaluate annually to reassess whether treatment should continue. [5] Safety - The most common side effects associated with alglucosidase alfa ( 10%) include hypersensitivity reactions (e.g. rash), fever, urticarial, flushing and increased blood pressure. [3] - Rare cases of hypersensitivity reactions and fluid overload in patients with infantileonset Pompe disease have been reported. - Patients receiving alglucosidase alfa should be monitored for IgG antibodies every three months for two years, then annually thereafter. Alternative Site of Care: - Use of an alternative site of care, including non-hospital outpatient infusion centers and home infusion services, is an accepted standard medical practice. These alternative sites of care offer high-quality services for patients and reduce the overall cost of care, as compared to a hospital-based infusion center. - All medications infused outside of a hospital setting (at an alternative site of care) have undergone an evaluation for safe infusion and development of infusion standards, including adverse drug reaction (ADR) management and reporting algorithms. - For use of an alternative site of care, every patient undergoes a patient assessment during the intake process by the infusion provider, which includes evaluation of individual clinical assessment parameters. These parameters may include, but are not limited to, previous tolerance of products (such as IVIG), assessment of kidney function, risk factors for developing thromboembolic events, and venous access. - For use of home infusion services, an assessment is conducted to determine whether or not the home is a safe, appropriate site of care, with adequate support for infusion in the home. - Because these alternative site of care providers need time to arrange for assessment and coordinate the first dose of each new medication, the first dose of infused medications may be covered in a hospital-based infusion center, if needed, to allow adequate time for a seamless transition of care. This may include arranging for delivery of medications and/or patient education, such as for self-administration of medications such as subcutaneous immune globulin (SCIG). dru392.0 Page 5 of 6

6 Codes Number Description HCPCS J0221 Injection, alglucosidase alfa, (Lumizyme), 10 mg ICD Glycogenosis: Pompe Disease References 1. Kishnani, PS, Steiner, RD, Bali, D, et al. Pompe disease diagnosis and management guideline. Genet Med. 2006;8: PMID: Darras, B, Craigen, W. Lysosomal acid maltase deficiency (glycogen storage disease II, Pompe disease) In: UpToDate, Hahn, SH. (Ed). UptoDate, Waltham, MA, Lumizyme [package insert]. Cambridge, MA: Genzyme Corporation; August Toscano, A, Schoser, B. Enzyme replacement therapy in late-onset Pompe disease: a systematic literature review. Journal of neurology Apr;260(4): PMID: Cupler, EJ, Berger, KI, Leshner, RT, et al. Consensus treatment recommendations for lateonset Pompe disease. Muscle & nerve Mar;45(3): PMID: dru392.0 Page 6 of 6