Subject:
Emapalumab-lzsg (Gamifant)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Gamifant is an interferon gamma (IFNã) blocking antibody indicated for the treatment of adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.
HLH is a rare, aggressive, and life-threatening condition of excessive immune activation in pediatric patients in which the patient’s immune cells can damage the body’s own liver, brain, and bone marrow. HLH occurs most commonly in infants from birth to 18 months of age, but has also been observed in children and adults of all ages. Primary or familial HLH is inherited, and patients usually develop symptoms within the first months or years of life. Based on epidemiological data, the incidence is estimated to be 1 case of HLH per 3000 inpatient admissions.
The safety and efficacy of Gamifant was studied in a multicenter, open-label, single-arm clinical trial of pediatric patients with suspected or confirmed primary HLH (NCT01818492). The patients had refractory, recurrent, or progressive disease during conventional HLH therapy, or were intolerant to conventional HLH therapy. The median age of enrolled patients was 1 year old. Of the 27 patients enrolled in the study, 20 patients (74%) completed the study and 7 patients (26%) were prematurely withdrawn. 22 patients (81%) enrolled into an open-label extension study which monitored patients for up to 1 year after HCT or after the last Gamifant infusion (NCT02069899). The study treatment duration was up to 8 weeks after which patients could continue treatment on the extension study. All patients received an initial starting dose of GAMIFANT of 1 mg/kg every 3 days. Subsequent doses could be increased to a maximum of 10 mg/kg based on clinical and laboratory parameters. All patients received dexamethasone as background HLH treatment, and cyclosporine A, intrathecal methotrexate, and intrathecal glucocorticoids were continued if administered prior to screening or at baseline.
The endpoints included overall response rate (ORR) at the end of treatment, defined as achievement of either a complete or partial response or HLH improvement. ORR was evaluated using an algorithm that included the following objective clinical and laboratory parameters: fever, splenomegaly, central nervous system symptoms, complete blood count, fibrinogen and/or D-dimer, ferritin, and soluble CD25 (also referred to as soluble interleukin-2 receptor) levels. Complete response was defined as normalization of all HLH abnormalities (i.e., no fever, no splenomegaly, neutrophils > 1x109/L, platelets > 100x109/L, ferritin < 2,000 g/L, fibrinogen > 1.50 g/L, D-dimer < 500 ug/L, normal CNS symptoms, no worsening of sCD25 > 2-fold baseline). Partial response was defined as normalization of ≥ 3HLH abnormalities. HLH improvement was defined as ≥ 3 HLH abnormalities improved by at least 50% from baseline. Of the 17 patients (63%) who experienced a response (p=0.013, 95%CI: 0.42-0.81), 7 (26%) experienced complete response, 8 (30%) experienced a partial response, and 2 (7.4%) had HLH improvement. Side effects included infections, hypertension, infusion-related reactions, low potassium, and fever. Ongoing phase 2 and 3 studies examining safety and efficacy with long-term follow-up are currently being conducted.
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
1. Gamifant (empalumab-lzsg) is considered medically necessary for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) in adult and pediatric (newborn and older) patients with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy if ALL of the following are met:
a. Member has a diagnosis of primary HLH assessed by a treating physician based on:
i. A molecular diagnosis or family history consistent with primary HLH. Members must not have a diagnosis of secondary HLH consequent to a proven rheumatic, metabolic or neoplastic disease; OR
ii. 5 out of following the 8 criteria
1. Fever
2. Splenomegaly
3. Cytopenias affecting 2 of 3 lineages in the peripheral blood
a. Hemoglobin < 90 g/L
b. Platelets < 100 x 109/L
c. Neutrophils < 1 x 109/L
4. Hypertriglyceridemia (fasting triglycerides > 3 mmol/L or ≥ 265 mg/dL) AND/OR Hypofibrinogenemia (≤ 1.5 g/L)
5. Hemophagocytosis in bone marrow, spleen, or lymph nodes with no evidence of malignancy
6. Low or absent NK-cell activity
7. Ferritin ≥ 500 mcg/L
8. Soluble CD25 ≥ 2400 U/Ml
b. Member must fulfill one of the following criteria as assessed by the treating physician:
i. Having not responded or not achieved a satisfactory response or having not maintained a satisfactory response to conventional HLH therapy (cyclosporine A, dexamethasone, and etoposide)
ii. Intolerance to conventional HLH treatments (cyclosporine A, dexamethasone, and etoposide)
c. Member must be up to 18 years of age at the diagnosis of HLH
d. Member must weigh more than 3 kg
e. Member must not have active infections caused by pathogens favored by IFNã neutralization (e.g., mycobacteria, Herpes Zoster virus, and Histoplasma Capsulatum).
f. Member should receive prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and fungal infections prior to Gamifant administration.
g. Members at risk for tuberculosis, or known to have a positive PPD test result, or positive IFNy release assay, should receive prophylaxis for tuberculosis before initiating treatment with Gamifant.
h. Members should be monitored for tuberculosis, adenovirus, EBV, and CMV every 2 weeks and as clinically indicated.
i. Member does not have concomitant disease or malformation severely affecting cardiovascular, pulmonary, CNS, liver, or renal function, or have presence of malignancy.
j. Vaccination with live vaccines will not to be administered during treatment and at least 4 weeks after the last dose of Gamifant.
k. Member is a candidate for but has not yet undergone a stem cell transplant
l. Member is taking dexamethasone concomitantly
2. When Gamifant (empalumab-lzsg) is considered medically necessary, initial therapy for 8 weeks will be approved based on the following FDA approved dose:
a. 1mg/kg given as an intravenous infusion over 1 hour twice per week. Doses may be increased base on clinical and laboratory criteria.
3. Gamifant (empalumab-lzsg) is considered medically necessary, for continued therapy every 6 months based on the following criteria
a. Achievement of positive clinical response
i. Compete response: normalization of all HLH abnormalities (no fever, no splenomegaly, neutrophils > 1 x 10^9/L, platelets >100x10^9/L, ferritin < 2,000microgram/L, fibrinogen >1.50g/L, D-dimer <500 microgram/L, normal CNS symptoms, no worsening of sCD25 > 2-fold baseline) OR
ii. Partial response: normalization of at least HLH abnormalities OR
iii. HLH improvement: at least 50% improvement from baseline of at least 3 HLH abnormalities
b. Continue treatment until
i. Hematopoietic allogeneic stem cell transplantation is performed
ii. Unacceptable toxicity (i.e. severe infection).
[INFORMATIONAL NOTE:
Pre-Medications Administer prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and for fungal infections prior to Gamifant administration.
Concomitant Medications For patients who are not receiving baseline dexamethasone treatment, begin dexamethasone at a daily dose of at least 5 to 10 mg/m2 the day before Gamifant treatment begins. For patients who were receiving baseline dexamethasone, they may continue their regular dose provided the dose is at least 5 mg/m2 . Dexamethasone can be tapered according to the judgment of the treating physician
Dose Modification Based on Response
| Treatment Day | GAMIFANT Dose | Criteria for Dose Increase |
| Day 1 | Starting Dose of 1 mg/kg | N/A |
| On Day 3 | Increase to 3 mg/kg | Unsatisfactory improvement in clinical condition, as
assessed by a healthcare provider AND at least one of
the following:
Fever – persistence or recurrence
Platelet count
If baseline < 50,000/mm3
and no improvement
to >50,000/mm3
If baseline > 50,000/mm3
and less than 30%
improvement
If baseline > 100,000/mm3 and decrease to <
100,000/mm3
Neutrophil count
If baseline < 500/mm3
and no improvement to >
500/mm3
If baseline > 500 -1000/mm3
and decrease to <
500/mm3
If baseline 1000-1500/mm3
and decrease to <
1000/ mm3
Ferritin (ng/mL)
If baseline ≥ 3000 ng/mL and < 20% decrease
If baseline < 3000 ng/mL and any increase to >
3000 ng/mL
Splenomegaly – any worsening
Coagulopathy (both D-Dimer and Fibrinogen must
apply)
D-Dimer
If abnormal at baseline and no
improvement
Fibrinogen (mg/dL)
If baseline levels ≤ 100 mg/dL and no
improvement
If baseline levels > 100 mg/dL) and any
decrease to < 100 mg/dL |
| From Day 6 onwards | Increase to 6 mg/kg |
| From Day 9 onwards | Increase to 10 mg/kg | Assessment by a healthcare provider that based on initial signs of response, a further increase in GAMIFANT dose can be of benefit |
4. Other use of Gamifant, including but not limited to secondary hemophagocytic lymphohistiocytosis, macrophage activation syndrome, juvenile arthritis are considered investigational.
Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.
Medicaid Coverage:
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Emapalumab-lzsg (Gamifant)
Gamifant (Emapalumab-lzsg)
References:
1. Gamifant [package insert]. Sobi Inc,. Waltham, MA. November 2018.
2. MICROMEDEX® 2.0 (Healthcare Series). DRUGDEX® Evaluations. Gamifant. Available at: http://www.thomsonhc.com. Accessed May 2019.
3. ClinicalTrials.gov. A Study to Investigate the Safety and Efficacy of an Anti-IFNy mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis. Available at https://clinicaltrials.gov/ct2/show/NCT01818492
4. McClain KL, Eckstein O. Clinical features and diagnosis of hemophagocytic lymphohistiocytosis. UpToDate. Updated 29 Oct, 2019. Accessed Dec 5 2018. Available from: www.uptodate.com.
5. McClain KL. Treatment and prognosis of hemophagocytic lymphohistiocytosis. UpToDate. Updated 12 Aug 2017. Accesssed Dec 5 2018. Available from: www.uptodate.com
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s)
does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2019 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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