Subject:
Patisiran (Onpattro)
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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Onpattro contains a transthyretin-directed small interfering RNA and is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
Hereditary transthyretin-mediated amyloidosis (hATTR) is a rare inherited progressive, life-threatening disease caused by a mutation in transthyretin (TTR) gene. This results in misfolded transthyretin(TTR) protein accumulating as amyloid fibrils in organs and tissues including the heart, nerves and gastrointestinal tract. Deposits in the peripheral nervous system and autonomic nervous system result in polyneuropathy, including peripheral neuropathy and disruption in involuntary body functions. hATTR affects approximately 50,000 individuals worldwide. If untreated, death occurs approximately 10 years after onset of hATTR amyloidosis. Current treatment options include managing symptomology, stabilizing the TTR protein and orthotropic liver transplantation to suppress production of TTR protein.
The efficacy of Onpattro was demonstrated in a multicenter clinical international, randomized, double-blind, placebo-controlled, clinical trial in adult patients with polyneuropathy caused by hATTR amyloidosis. Patients were randomized in a 2:1 ratio. 148 patients were randomized to receive Onpattro 0.3 mg/kg or and 77 patients were randomized to placebo, via intravenous infusion once every 3 weeks for 18 months. All patients received premedication with a corticosteroid, acetaminophen, and H1 and H2 blockers. Ninety-three percent of Onpattro-treated patients and 62% of placebo-treated patients completed 18 months of the assigned treatment. The primary efficacy endpoint was the change from baseline to Month 18 in the modified Neuropathy Impairment Score +7 (mNIS+7). At 18 months, the least-squares (LS) mean change from baseline in the primary endpoint, modified Neuropathy Impairment Score plus 7 (mNIS+7), was lower with patisiran compared to placebo with a treatment difference of -34.0 (p<0.001). Furthermore, the LS mean change from baseline to 18 months in mNIS+7 among patisiran treated patients was -6.0, indicating an overall improvement in polyneuropathy. At 18 months, 56% of patients treated with patisiran demonstrated reversal in neuropathy impairment (change less than 0 from baseline in mNIS+7) compared to 4% of patients in the placebo arm (odds ratio [OR] of improvement with patisiran vs placebo, 39.9; p<0.001).
The modified Neuropathy Impairment Scores + 7 (mNIS+7) assessment tool is a 304 point composite measure of neurologic impairment. This measure accounts for motor strength and weakness, quantitative sensory testing, reflexes, nerve conduction studies and autonomic function (postural blood pressure). An increase in mNIS +7 score or any of the components of the assessment indicate worsening impairment.
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
1. Please refer to a separate policy on Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) under the Drug Section.
2. Patisiran (Onpattro) is medically necessary for the following FDA approved indications when ALL of the following criteria are met
- For the treatment of treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults with a documented transthyretin TTR mutation (documentation of medical records required)
- The prescriber is a specialist in the area of the patient’s diagnosis (e.g. cardiologist, neurologist) or has consulted with a specialist in the area of the patient’s diagnosis AND
- Be at least 18 years of age AND
- Patient has a definitive diagnosis of hATTR amyloidosis/FAP as documented by amyloid deposition on tissue biopsy and identification of a pathogenic TTR variant using genetic testing (documentation of medical records required); AND
- Used for the treatment of polyneuropathy as demonstrated by at least TWO of the following criteria (documentation of medical records required)
a. Symptoms consistent with the polyneuropathy of hATTR amyloidosis including any of the following
i. Peripheral sensorimotor polyneuropathy (e.g., tingling or increased pain in the hands, feet, hands and/or arms, loss of feeling in the hands and/or feet, numbness or tingling in the wrists, carpal tunnel syndrome, loss of ability to sense temperature, difficulty with fine motor skills, weakness in the legs, difficulty walking, seizures, headaches); or
ii. Autonomic neuropathy symptoms (e.g., orthostasis, abnormal sweating, sexual dysfunction, recurrent urinary tract infection, dysautonomia [constipation and/or diarrhea, nausea, vomiting, anorexia, early satiety]);
b. Abnormal nerve conduction studies are consistent with polyneuropathy;
c. Abnormal neurological examination is suggestive of neuropathy; AND
- Patient’s peripheral neuropathy is attributed to hATTR/FAP and other causes of neuropathy have been excluded; AND
- Baseline polyneuropathy disability (PND) score ≤ IIIb OR baseline Familial Amyloid Polyneuropathy (FAP) Stage 1 or 2 (documentation of medical records required) AND
- Baseline in strength/weakness has been documented using an objective clinical measuring tool (e.g. Medical Research Council (MRC) muscle strength, etc) (documentation of medical records required); AND
- Patient has not been the recipient of an orthotopic liver transplant (OLT)
- Patisiran (Onpattro) is not to be used in combination with inotersen (Tegsedi)
[INFORMATIONAL NOTE:
- In the Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy(APOLLO) inclusion criteria of individuals ≥ 18 years old was followed
- In the Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy(APOLLO) exclusion criteria of individuals with an orthotopic liver transplant was followed
- Polyneuropathy disability (PND) score allows for assessing and monitoring disease severity. It primarily use factors such as a patient’s ability to walk in assessing patient outcome.
o PND Score
§ I: preserved walking, sensory disturbances
§ II: impaired walking but can walk without stick or crutch
§ IIIa: walk with 1 stick or crutch
§ IIIb: walk with 2 sticks or crutches
§ IV: confined to wheelchair or bedridden
- Medical Research Council Manual Muscle Testing scale. This method involves testing key muscles from the upper and lower extremities against the examiner’s resistance and grading the patient’s strength on a 0 to 5 scale accordingly:
o 0 No muscle activation
o 1 Trace muscle activation, such as a twitch, without achieving full range of motion
o 2 Muscle activation with gravity eliminated, achieving full range of motion
o 3 Muscle activation against gravity, full range of motion
o 4 Muscle activation against some resistance, full range of motion
o 5 Muscle activation against examiner’s full resistance, full range of motion
- Alnylam Act: Alnylam is sponsoring no-charge third-party genetic testing and counseling for individuals who may carry gene mutations known to be associated with either hereditary ATTR (hATTR) amyloidosis. More information available at (http://www.alnylam.com/medical-professional-resources/genetic-testing-counseling/)
- Portuguese Familial Amyloid Polyneuropathy (FAP) staging system is a method to access and monitor disease severity in patients with Hereditary transthyretin-mediated (hATTR) amyloidosis. This staging system primarily uses the patient’s ability to walk to assess patient’s outcomes. Includes three stages:
- Stage 1: Unimpaired ambulation
- Stage 2: Assistance with ambulation required
- Stage 3: Wheelchair bound or bedridden.]
3. When patisiran (Onpattro) is medically necessary, initial therapy will be approved for 12 months at the FDA recommended dosage of:
- Recommended dose of patisiran is 0.3 mg/kg based on actual body weight and is administered via intravenous (IV) infusion once every three weeks for patients weighing less than 100 kg.
- Patients weighing 100 kg or more, the recommended dose is 30 mg every three weeks.
- Patient is receiving supplementation with Vitamin A at the recommended daily allowance.
[INFORMATIONAL NOTE: The FDA approved package insert notes the following:
- Filter and dilute prior to administration
- Infuse over approximately 80 minutes.
- Premedications within 60 minutes prior to patisiran administration with a IV corticosteroid, oral acetaminophen, IV antihistamines(H1 and H2 Blockers)
- Supplementation at recommended daily allowance of Vitamin A is advised.]
4. Patisiran (Onpattro) is medically necessary for annual approval when all of the following are met:
- Patient has previously received treatment with patisiran AND
- Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: severe infusion-related reactions, ocular symptoms related to hypovitaminosis A, etc; AND
- Disease response compared to pre-treatment baseline as evidenced by stabilization or improvement in one or more of the following:
- Signs and symptoms of neuropathy
- MRC muscle strength
5. Other uses of paitisiran (Onpattro) are considered investigational for the following conditions: :
- Treatment of individuals younger than 18 years of age
- Treatment of individuals without the presence of a polyneuropathy symptom associated with hATTR amyloidosis
- Other form of amyloidosis that is not due to a genetic mutation in the TTR gene
Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this drug. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.
**Note: Bullet 1 of the policy section referring to Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) does not apply for Medicare Advantage Products.
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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:
Patisiran (Onpattro)
Onpattro (Patisiran)
Hereditary Transthyretin-Mediated Amyloidosis (hATTR)
hATTR (Hereditary Transthyretin-Mediated Amyloidosis)
References:
1. Alnylam. Onpattro Package Insert. Cambridge, MA. February 2020.
2. Patisiran. Clinicaltrial.gov. Accessed on 3/20/2020. Available at: https://clinicaltrials.gov/ct2/show/NCT01960348
3. Adams, D., Suhr, O., Dyck, P., Litchy, W., Leahy, R., Chen, J., Gollob, J., et al. (n.d.). Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy.(Report). BMC Neurology, 17(1), 181. doi:10.1186/s12883-017-0948-5
4. Rarediseases.info.nih.gov. (2018). Familial transthyretin amyloidosis | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [online] Available at: https://rarediseases.info.nih.gov/diseases/656/familial-transthyretin-amyloidosis [Accessed 1 Sep. 2018].
5. Inês M, Coelho T, Conceicao I, Saramago P, Carvalho M, Costa J. Life Expectancy And Costs of Transthyretin Familial Amyloid Polyneuropathy. Value in Health. 2017;20(9):A553.
6. Gertz, Morie A. “Hereditary ATTR Amyloidosis: Burden of Illness and Diagnostic Challenges.” AJMC, www.ajmc.com/journals/supplement/2017/hereditary-attr-amyloidosis-burden-of-illness-and-diagnostic-challenges/hereditary-attr-amyloidosis-burden-of-illness-and-diagnostic-challenges-article?p=2.
7. Gonzalez-Duarte,Alejandra, et al. Changes in Neuropathy Stage in Patients with Hereditary Transthyretin-Mediated Amyloidosis Following Treatment with Patisiran, an Investigational RNAi Therapeutic:An Analysis from the Phase 3 APOLLO Study.
8. Adams, D., Gonzalez-Duarte, A., O’Riordan, W., Yang, C., Ueda, M., Kristen, A., Tournev, I., et al. (n.d.). Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. The New England Journal of Medicine, 379(1), 11–21. doi:10.1056/NEJMoa1716153
9. Naqvi U, Sherman Al. Muscle Strength Grading. [Updated 2018 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK436008/
10. “Genetic Testing & Counseling.” Alnylam, www.alnylam.com/medical-professional-resources/genetic-testing-counseling/.
11. Ionis Pharmaceuticals. Tegsedi Package Insert. Carlsbad, CA. October 2018.
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 2020 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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