Subject:
Copanlisib (Aliqopa)
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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Follicular lymphoma is a slow-growing type of non-Hodgkin lymphoma, which can relapse even after multiple treatments. Despite being the most common type of non-Hodgkin lymphoma, there is an unmet need of additional treatment options for relapsed follicular lymphoma. The National Cancer Institute at the National Insititutes of Health estimates that approximately 72,240 people in the United States will be diagnosed with some form of non-Hodgkin lymphoma this year; approximately 20,140 patients with non-Hodgkin lymphoma will die from the disease in 2017.
AliqopaTM (copanlisib) is indicated for the treatment of adults with relapsed follicular lymphoma who have received at least two prior systemic treatments. Aliqopa was granted accelerated approval with orphan drug designation based on overall response rate seen in clinical studies; further trials are required to confirm Aliqopa’s clinical benefit and the sponsor is currently conducting these studies. Aliqopa is a kinase inhibitor with activity predominantly against phosphatidylinositol-3-kinase (PI3K) isoforms expressed in malignant B cells. Aliqopa has been shown to induce tumor cell death by apoptosis and inhibition of proliferation of primary malignant B cell lines.
The safety and efficacy of Aliqopa was evaluated in a single-arm trial (CHRONOS-1 Study) that included 104 patients with follicular B-cell non-Hodgkin lymphoma who had relapsed disease after at least two prior treatments. Patients received 60 mg of Aliqopa, and treatment continued until disease progression or unacceptable toxicity. The trial measured how many patients experienced complete or partial shrinkage of their tumors after treatment (overall response rate). 59% of patients (95% CI: 49, 68) had a complete or partial response for a median 12.2 months. The median time to response was 1.7 months (range 1.3 to 9.7 months). Side effects include infections, hyperglycemia, hypertension, non-infectious pneumonitis, neutropenia, and severe skin reactions. Women who are pregnant or breastfeeding should not take Aliqopa because it may cause harm to a developing fetus or newborn baby.
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
The requirements of the Horizon BCBSNJ Copanlisib (Aliqopa) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).
1. Copanlisib (AliqopaTM) is medically necessary for the FDA-approved indication when ALL of the following criteria are met:
a. Member has a confirmed diagnosis of follicular lymphoma
b. Member has relapsed disease, which is defined as an appearance of any new lesion, a 50% increase in the longest diameter of a previously identified lesion, or new/recurrent involvement of the bone marrow from baseline
c. Member has tried at least two or more systemic treatments, including rituximab and an alkylating agent
d. ECOG score 0-1
e. Member has negative pregnancy testing and is using effective contraceptive method
f, Member will be using copanlisib (Aliqopa) as monotherapy
g. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis
[INFORMATIONAL NOTE: Per the FDA approved package insert, copanlisib can cause fetal harm when administered to a pregnant woman. Conduct pregnancy testing prior to initiation of copanlisib treatment. Advise female patients of reproductive potential to use highly effective contraception during treatment with copanlisib.
Per pivotal clinical trial for copanlisib (CHRONOS-1 study), key inclusion criteria for patients consisted of having confirmed indolent B-Cell NHL diagnosis who had relapsed or refractory disease after >2 lines of therapy, which was composed of rituximab and alkylating agents, confirmed an Eastern Cooperative Oncology Group (ECOG) performance status of <2, and a life expectancy of >3 months.]
2. When copanlisib (AliqopaTM) is considered medically necessary, initial therapy will be approved for 6 months based on FDA-approved labeling:
a. 60 mg administered as a 1-hour intravenous infusion on Days 1, 8, and 15 of a 28-day treatment cycle on an intermittent schedule (three weeks on and one week off).
b. For patients requiring concomitant use with a strong CYP3A inhibitor, reduce the starting dose to 45 mg administered as a 1-hour intravenous infusion on Days 1, 8, and 15 of a 28-day treatment cycle on an intermittent schedule (three weeks on and one week off).
[INFORMATIONAL NOTE: Per the FDA approved package insert, concomitant use of copanlisib with strong CYP3A inhibitors increases the area under the plasma drug concentration (AUC). If concomitant use with strong CYP3A inhibitors cannot be avoided, reduce the copanlisib dose to 45 mg. An increase in the copanlisib AUC may increase the risk of adverse reactions.
Cytochrome P450 3A4 (abbreviated CYP3A4) is an important enzyme in the body, mainly found in the liver and in the intestine, that is essential for metabolism and removal of drugs from the body. CYP3A4 inhibitors are drugs that decrease the activity of CYP3A4, therefore, increasing the plasma concentration of drugs that are CYP3A4 substrates, which can possibly cause toxicity of the given drug. Examples of strong CYP3A inhibitors include: boceprevir, clarithromycin, cobicistat, conivaptan, danoprevir and ritonavir, diltiazem, elvitegravir and ritonavir, grapefruit juicec , idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole, ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, troleandomycin, voriconazole.]
3. Continued therapy with copanlisib (AliqopaTM) will be approved every 6 months based on the following criteria:
a. Member has not experienced disease progression or unacceptable toxicity while receiving treatment with copanlisib (AliqopaTM).
b. Member does not have active infection of grade 3 or higher or suspected pneumocystis jiroveci pneumonia (PJP) infection of any grade
c. Fasting blood glucose <160 mg/dL or less or random/nonfasting blood glucose of <200 mg/dL
d. Blood pressure is <150/90 based on two consecutive BP measurements >15 minutes apart AND member does not have elevated BP with life-threatening consequences
e. Member does not have active grade 2 or higher non-infectious pneumonitis (NIP)
f. Member does not have unresolved toxic or life-threatening severe cutaneous reaction
g. Platelet levels >75.0 x 109 /L and recovery occurs within 21 days
h. Member has negative pregnancy testing and is using effective contraceptive method
[INFORMATIONAL NOTE: Per the FDA approved package insert, copanlisib has the following warnings and precautions: serious opportunistic infections, including pneumocystis jiroveci pneumonia, hyperglycemia, hypertension, non-infectious pneumonitis, neutropenia, severe cutaneous reactions, and embryo-fetal toxicity]
4. Copanlisib (Aliqopa) is considered medically necessary for the off-label indications that are 2A or better recommendations on National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium – copanlisib. Available at: https://www.nccn.org/professionals/drug_compendium/content/
5. All other uses of copanlisib (Aliqopa) are considered investigational.
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.
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:
Copanlisib (Aliqopa)
Aliqopa (Copanlisib)
References:
1. AliqopaTM product information. Bayer Healthcare Pharmaceuticals, Inc. Whippany, NJ. February 2020.
2. Dreyling M, Morschhauser F, Bouabdallah K, et al. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017;28(9):2169-2178.
3. UpToDate. Treatment of relapsed or refractory follicular lymphoma. Available at: https://www.uptodate.com/contents/treatment-of-relapsed-or-refractory-follicular-lymphoma. Literature review current through: Aug 2017.This topic last updated: Sep 19, 2017.
4. ClinicalTrials.gov. Copanlisib Pharmacodynamic Study. Available at: https://clinicaltrials.gov/ct2/show/NCT02155582?term=copanlisib&recrs=e&rank=1. June 16, 2017. Accessed May 2019.
5. Micromedex® Healthcare Series. n.d. Thomson Healthcare, Greenwood Village, CO. August 2020.
6. Lim SY, Menzies AM, Rizos H. Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma. Cancer. 2017;123(S11):2118-2129.
7. FDA News Press Release. FDA approves new treatment for adults with relapsed follicular lymphoma. September 14, 2017.
8. Aliqopa [copanlisib]. (Formulary Submission Dossier). Bayer HealthCare Pharmaceuticals, Inc. September 2017.
9. ClinicalTrials.gov. Trial List for Copanlisib. 2020. Available at: https://clinicaltrials.gov/ct2/results?term=copanlisib. Accessed August 25, 2020.
10. Copanlisib (Aliqopa). National Comprehensive Cancer Network Compendium. 2020. Available at https://www.nccn.org/professionals/drug_compendium/content/. Accessed August 25, 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*
J9057
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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