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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:204
Effective Date: 05/30/2020
Original Policy Date:04/28/2020
Last Review Date:
Date Published to Web: 04/28/2020
Subject:
Peanut (Arachis hypogaea) Allergen Powder-dnfp (Palforzia)

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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Peanut allergy is one of the most serious food allergies due to the potential for severe allergic reactions which can be life threatening and the lifelong persistence of the allergy. Only about 20% of children will outgrow their peanut allergy. Food allergies arise from a failure of the immune system to generate or maintain a tolerance to specific food proteins. The body’s immune system reacts to even small amounts of the food as a harmful substance. IgE-mediated food allergy reactions, such as peanut allergy, are characterized by quick onset of symptoms, sometimes within seconds, after ingestion of or exposure to the protein. Symptoms can range from mild to severe, with skin reactions such as hives, itchiness, and swelling, to more severe acute uticaria or angioedema, which can progress to more serious reactions such as anaphylaxis, hypotension, and multiple organ dysfunction syndrome. Antihistamines and epinephrine are used to treat allergic reactions.

On January 31, 2020, the U.S. Food and Drug Administration (FDA) approved Aimmune Therapeutics’ Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp], an oral immunotherapy (OIT) indicated to help reduce the severity of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut.

OIT is a desensitization process in which small doses are initially given, followed by gradual, incremental increases, resulting in the ability of the body to mitigate allergic reactions to peanuts over time. Palforzia reduces the severity of allergic reactions due to peanut ingestion or exposure; it does not replace the need to follow a peanut-free diet and limit exposure to peanuts. It is not used to treat allergic reactions. Treatment with Palforzia is approved for therapy initiation in individuals ages 4 through 17 years with a confirmed diagnosis of peanut allergy and may be continued in individuals ages 18 years of age and older. Palforzia powder is for oral administration only; it supplied in capsules and sachets that are stored in the refrigerator and mixed with semisolid foods before ingesting.

Treatment with Palforzia is administered in 3 sequential phases: Initial Dose Escalation, Up-Dosing, and Maintenance. Initial Dose Escalation may be administered to patients aged 4 through 17 years. Up-Dosing and Maintenance may be continued in patients 4 years of age and older.

The approval was based on a study of more than 500 individuals highly allergic to peanuts, which evaluated how well patients tolerated an oral peanut challenge after 6 months of maintenance therapy. The efficacy of Palforzia for the mitigation of allergic reactions, including anaphylaxis, in patients with peanut allergy was investigated in Study 1 – PALISADE trial (NCT02635776). Study 1 was a phase 3, randomized, double-blind, placebo-controlled study of the efficacy and safety of Palforzia in patients with 13 peanut allergy aged 4 through 55 years in the United States, Canada, and Europe. The primary analysis population consisted of 496 subjects (Palforzia, N = 372; placebo, N = 124) aged 4 through 17 years in the intent-to-treat (ITT) population who received at least 1 dose of study treatment. After an Initial Dose Escalation ranging from 0.5 mg to 6 mg on Day 1 and confirmation of tolerability of the 3 mg dose on Day 2, subjects underwent Up-Dosing for 20-40 weeks starting at 3 mg until the 300 mg dose was reached. The Up-Dosing period varied for each subject depending on how the dose was tolerated. Subjects then underwent 24-28 weeks of Maintenance immunotherapy with 300 mg Palforzia until the end of the study. At the end of the Maintenance period, subjects completed an exit DBPCFC (double-blind, placebo-controlled food challenge) to approximate an accidental exposure to peanut and to assess their ability to tolerate increasing amounts of peanut protein with no more than mild allergic symptoms.

The primary efficacy endpoint was the percentage of subjects tolerating a single dose of 600 mg peanut protein in the exit DBPCFC with no more than mild allergic symptoms after 6 months of Maintenance treatment. The primary efficacy endpoint was considered met if the lower bound of the 95% confidence interval (CI) for the difference in response rates between the treatment and the placebo groups was greater than the pre-specified margin of 15%. Key secondary endpoints included the comparisons of the response rates after single doses of 300 mg and 1000 mg peanut protein as well as a comparison of the maximum severity of symptoms at any challenge dose of peanut protein during the exit DBPCFC. The key secondary endpoints were to be evaluated for statistical significance (two-sided p < 0.05) only if the primary endpoint and all the preceding tests in the hierarchy were statistically significant in favor of Palforzia. The proportion of subjects who tolerated single highest doses of 300 mg, 600 mg, and 1000 mg with no more than mild symptoms at the exit DBPCFC were 76.6%, 67.2%, and 50.3%, respectively for Palforzia-treated subjects compared with 8.1%, 4.0%, and 2.4% for placebo-treated subjects. The results showed that 67.2% of Palforzia recipients tolerated a 600 mg dose of peanut protein in the challenge with no more than mild allergic symptoms, compared to 4.0% of placebo recipients.

The most common adverse reactions reported in subjects treated with Palforzia (incidence ≥ 5% and at least 5 percentage points greater than that reported in subjects treated with placebo) are abdominal pain, vomiting, nausea, oral pruritus, oral paresthesia, throat irritation, cough, rhinorrhea, sneezing, throat tightness, wheezing, dyspnea, pruritus, urticaria, anaphylactic reaction, and ear pruritus.

Palfrozia is contraindicated in those with uncontrolled asthma, and history of eosinophilic esophagitis or other eosinophilic gastrointestinal disease.

As per the FDA labeled package insert, Palforzia has a boxed warning for anaphylaxis:

      • Palforzia can cause anaphylaxis, which may be life-threatening and can occur at any time during Palforzia therapy
      • Prescribe injectable epinephrine, instruct and train patients on its appropriate use, and instruct patients to seek immediate medical care upon its use.
      • Do not administer Palforzia to patients with uncontrolled asthma
      • Dose modifications may be necessary following an anaphylactic reaction.
      • Observe patients during and after administration of the Initial Dose Escalation and the first dose of each Up-Dosing level, for at least 60 minutes
      • Because of the risk of anaphylaxis, Palforzia is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Palforzia REMS

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
    I. Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp] is considered medically necessary for the FDA approved indication of mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut, when ALL of the following are met:
          a. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis

          b. The member has a diagnosed peanut allergy (documentation required – e.g. member history of systemic reactions to peanuts, skin prick test to peanut resulting in a mean wheal diameter of 8 mm compared to control, serum IgE levels to peanut ≥ 14 kUA/L)

          c. The member is 4-17 years of age at the time of initiating therapy

          d. The initial and up-dosing phases will administered by a healthcare professional in an office setting

          e. Provider, patient, and facility must be enrolled in the REMS program

          f. The member has epinephrine injection on hand as evidenced by ONE of the following:

              i. There is a claim for epinephrine injection in the past 365 days OR

              ii. The prescriber has provided information that the member has epinephrine injection on hand while on therapy with the requested agent

          g. The member does not have any FDA labeled contraindication(s) to the requested agent (e.g. uncontrolled asthma, history of eosinophilic esophagitis or other eosinophilic gastrointestinal disease)

          h. The requested quantity (dose) is within the FDA labeled dosing


    II. When Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp] is considered medically necessary, therapy will be approved for a period of 12 months at the following FDA approved doses:

          Table 1: Dosing Configuration for Initial Dose Escalation (Single Day Dose Escalation)
          Initial Dose Escalation (Single-Day Dose Escalation)
          Dose Level
          Total Dose
          Dose Configuration
          A
          0.5 mg
          One 0.5 mg capsule
          B
          1 mg
          One 1 mg capsule
          C
          1.5 mg
          One 0.5 mg capsule; One 1 mg capsule
          D
          3 mg
          Three 1 mg capsules
          E
          6 mg
          Six 1 mg capsules
          Initial Dose Escalation supplied as a single card consisting of 5 blisters containing a total of 13 capsules

          Table 2: Daily Dosing Configuration for Up-Dosing
          Daily Dosing for Up-Dosing Phase
          Dose Level
          Total Daily Dose
          Duration
          Daily Dose Configuration
          1
          3 mg
          2 weeks
          Three 1 mg capsules
          2
          6 mg
          2 weeks
          Six 1 mg capsules
          3
          12 mg
          2 weeks
          Two 1 mg capsules; One 10 mg capsule
          4
          20 mg
          2 weeks
          One 20 mg capsule
          5
          40 mg
          2 weeks
          Two 20 mg capsules
          6
          80 mg
          2 weeks
          Four 20 mg capsules
          7
          120 mg
          2 weeks
          One 20 mg capsule; One 100 mg capsule
          8
          160 mg
          2 weeks
          Three 20 mg capsules; One 100 mg capsle
          9
          200 mg
          2 weeks
          Two 100 mg capsules
          10
          240 mg
          2 weeks
          Two 20 mg capsules; Two 100 mg capsules
          11
          300 mg
          2 weeks
          One 300 mg sachet

            Table 3: Daily Dosing Configuration for Maintenance
            Dose Level
            Total Daily Dose
            Daily Dose Configuration
            11
            300mg
            One 300 mg sachet

            [INFORMATIONAL NOTE: As per the FDA labeled package insert, dosing and administration section:

            Initial Dose Escalation

              Initial Dose Escalation is administered on a single day under the supervision of a health care professional in a health care setting with the ability to manage potentially severe allergic reactions, including anaphylaxis.
              Initial Dose Escalation is administered in sequential order on a single day beginning at Level A (5 Levels A-E, 0.5-6 mg; Table 1).
              Each dose should be separated by an observation period of 20 to 30 minutes.
              No dose level should be omitted.
              Observe patients after the last dose for at least 60 minutes until suitable for discharge.
              Discontinue PALFORZIA if symptoms requiring medical intervention (e.g., use of epinephrine) occur with any dose during Initial Dose Escalation.
              Patients who tolerate at least the 3 mg single dose (Level D) of PALFORZIA during Initial Dose Escalation must return to the health care setting for initiation of Up-Dosing.
              If possible, begin Up-Dosing the day after Initial Dose Escalation.
              Repeat Initial Dose Escalation in a health care setting if the patient is unable to begin Up-Dosing within 4 days.

            Up-Dosing
              Complete Initial Dose Escalation before starting Up-Dosing.
              Up-Dosing consists of 11 dose levels and is initiated at a 3 mg dose (Level 1).
              The first dose of each new Up-Dosing level is administered under the supervision of a health care professional in a health care setting with the ability to manage potentially severe allergic reactions, including anaphylaxis.
              Observe patients after administering the first dose of a new Up-Dosing level for at least 60 minutes until suitable for discharge.
              If the patient tolerates the first dose of the increased dose level, the patient may continue that dose level at home. Each dose should be consumed daily with a meal at approximately the same time each day, preferably in the evening.
              Administer all the dose levels in Table 2 in sequential order at 2-week intervals if tolerated.
              No dose level should be omitted.
              Do not progress through Up-Dosing more rapidly than shown in Table 2.
              No more than 1 dose should be consumed per day. Instruct patients not to consume a dose at home on the same day as a dose consumed in the clinic.
              Consider dose modification or discontinuation for patients who do not tolerate Up-Dosing as 70 described in Table 2.
              Maintenance
                Complete all dose levels of Up-Dosing before starting Maintenance.
                The Maintenance dose of PALFORZIA is 300 mg daily.
                Daily Maintenance is required to maintain the effect of PALFORZIA.
                During Maintenance, contact patient at regular intervals to assess for adverse reactions to PALFORZIA.

              Dose Modification

              Dose modifications are not appropriate during Initial Dose Escalation

              Temporary dose modification of Palforzia may be required for patients who experience allergic reactions during Up-Dosing or Maintenance, for patients who miss doses, or for practical reasons of patient management. Allergic reactions, including gastrointestinal reactions that are severe, recurrent, bothersome, or last longer than 90 minutes during Up-Dosing or Maintenance should be actively managed with dose modifications. Use clinical judgment to determine the best course of action, which can include maintaining the dose level for longer than 2 weeks, reducing, withholding, or discontinuing Palforzia doses.

              Management of Consecutive Missed Doses

              Following 1 to 2 consecutive days of missed doses, patients may resume Palforzia at the same dose level. Data are insufficient to inform resumption of Palforzia following 3 or more consecutive days of missed doses. Patients who miss 3 or more consecutive days of Palforzia should consult their healthcare providers; resumption of Palforzia should be done under medical supervision.

              Discontinuation

              Discontinue treatment with PALFORZIA for:
              • Patients who are unable to tolerate doses up to and including the 3 mg dose during Initial Dose Escalation
              • Patients with suspected eosinophilic esophagitis
              • Patients unable to comply with the daily dosing requirements
              • Patients with recurrent asthma exacerbations or persistent loss of asthma control]

        III. Continued therapy with Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp] will be approved annually based on the FDA approved dosing above when ALL of the following are met:
            a. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., allergist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis

            b. Member has been previously approved for the requested agent

            c. Member has had clinical benefit with the requested agent (e.g. member has no more than mild symptoms during a double-blind, placebo-controlled food challenge (DBPCFC), member shows reduction in severity of symptoms at any challenge dose of peanut protein, etc.)

            d. Member was able to tolerate doses up to and including the 3 mg dose during Initial Dose Escalation

            e. Member is adherent to daily dosing requirements

            f. If the member requires up-dosing, it will administered by a healthcare professional in an office setting

            g. Member has epinephrine injection on hand as evidenced by ONE of the following:

                i. There is a claim for epinephrine injection in the past 365 days OR

                ii. The prescriber has provided information that the member has epinephrine injection on hand while on therapy with the requested agent

            h. Member does not have any FDA labeled contraindication(s) to the requested agent (e.g. uncontrolled asthma, history of eosinophilic esophagitis or other eosinophilic gastrointestinal disease)

            i. The requested quantity (dose) is within the FDA labeled dosing

        IV. Other uses of Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp] are considered investigational.
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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:
      Peanut (Arachis hypogaea) Allergen Powder-dnfp (Palforzia)
      Palforzia (Peanut (Arachis hypogaea) Allergen Powder-dnfp

      References:
      1. Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp] Powder for oral administration, prescribing information. Aimmune Therapeutics, Inc. Brisbane, California. January 2020.

      2. ClinicalTrials.gov. Peanut Allergen Powder. Available at https://clinicaltrials.gov/ct2/results?cond=&term=peanut+allergen+powder&cntry=&state=&city=&dist=. Accessed March 3, 2020.

      3. ClinicalTrials.gov. Peanut Allergy Oral Immunotherapy Study for AR101 for Desensitization in Children and Adults (PALISADE). NCT02635776. Available at: https://clinicaltrials.gov/ct2/show/NCT02635776

      4. Real-World AR101 Market-Supporting Experience Study in Peanut-Allergic Children. NCT03126227. Available at: https://clinicaltrials.gov/ct2/show/NCT03126227?term=NCT03126227&draw=2&rank=1

      5. Togias A, Cooper SF, Acebal ML, et al. Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. J Allergy Clin Immunol. 2017;139(1):29-44.

      6. Palforzia. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2020

      7. Palforzia. New Drug Review Report. IPD Analytics. February 2020.

      8. Oral Immunotherapy and Viaskin Peanut for Peanut Allergy: Effectiveness and Value. Published July 10, 2019. ICER Report. Available at: https://icer-review.org/wp-content/uploads/2018/12/ICER_PeanutAllergy_Final_Report_071019.pdf

      9. AMCP Dossier for Palforzia. Aimmune Therapeutics. Brisbane, CA. 2020.
        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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