Motixafortide (Aphexda)

Number: 1046

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References


Policy

Scope of Policy

This Clinical Policy Bulletin addresses motixafortide (Aphexda) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

  1. Criteria for Initial Approval

    Hematopoietic Stem Cell Mobilization

    Aetna considers motixafortide (Aphexda) medically necessary in members with multiple myeloma when all of the following criteria are met:

    1. The requested medication will be used to mobilize hematopoietic stem cells for collection, and
    2. The requested medication will be administered after the member has received four daily doses of G-CSF (e.g., filgrastim), and
    3. The requested medication will not be used beyond two doses or after completion of stem cell harvest/apheresis.

    Aetna considers all other indications as experimental, investigational, or unproven.

  2. Continuation of Therapy

    Aetna considers continuation of motixafortide (Aphexda) therapy medically necessary for all members (including new members) who meet all initial medical necessity criteria requirements.

Dosage and Administration

Motixafortide is supplied as Aphexda 62 mg as a lyophilized powder in a single-dose vial for reconstitution for subcutaneous injection.

Aphexda dosage and administration is as follows:

  • Initiate Aphexda treatment after filgrastim has been administered daily for 4 days.
  • Recommended dosage is 1.25 mg/kg actual body weight by subcutaneous injection 10 to 14 hours prior to initiation of apheresis.
  • A second dose of Aphexda can be administered 10 to 14 hours prior to a third apheresis.
  • Administer Aphexda only in a setting where personnel and therapies are immediately available for the treatment of anaphylaxis and other systemic reactions.
  • Monitor individuals for signs and symptoms of hypersensitivity reactions for one hour following administration of Aphexda and manage reactions promptly.
  • Refer to Aphexda full prescribing information for instructions on preparation and administration.

Source: BioLineRx USA, 2023


Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

Other CPT codes related to the CPB:

38204 Management of recipient hematopoietic progenitor cell donor search and cell acquisition
38206 Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous
38207 Transplant preparation of hematopoietic progenitor cells; cryopreservation and storage
38241 Hematopoietic progenitor cell (HPC); autologous transplantation
96401 Chemotherapy administration, subcutaneous or intramuscular; non-hormonal anti-neoplastic

HCPCS codes covered if selection criteria are met:

J2277 Injection, motixafortide, 0.25 mg

Other HCPCS codes related to the CPB:

J1442 Injection, filgrastim (g-csf), excludes biosimilars, 1 microgram
J1447 Injection, tbo-filgrastim, 1 microgram
Q5101 Injection, filgrastim-sndz, biosimilar, (zarxio), 1 microgram
Q5110 Injection, filgrastim-aafi, biosimilar, (nivestym), 1 microgram
Q5125 Injection, filgrastim-ayow, biosimilar, (releuko), 1 microgram
S2150 Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre-and post-transplant care in the global definition

ICD-10 codes covered if selection criteria are met:

C90.00 - C90.02 Multiple myeloma

Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

  • Aphexda is indicated in combination with filgrastim (G-CSF [granulocyte-colony stimulating factor]) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

Motixafortide is available as Aphexda (BioLineRx USA Inc) and inhibits the C-X-C Motif Chemokine Receptor 4 (CXCR4) and blocks the binding of its cognate ligand, stromal-derived factor-1α (SDF-1α)/C-X-C Motif Chemokine Ligand 12 (CXCL 12). SDF-1α and CXCR4 are involved in the trafficking and homing of human hematopoietic stem cells to the marrow compartment. Once in the marrow, stem cell CXCR4 can help anchor these cells to the marrow matrix, either directly vis SDF-1α or through the induction of other adhesion molecules. Aphexda treatment, in mice, rats, dogs, and humans, has resulted in leukocytosis and elevations in circulating hematopoietic stem and progenitor cells into the peripheral circulation. A rodent transplantation model showed that Aphexda mobilized stem cells were capable of engraftment with long-term repopulating capacity (BioLineRx USA, 2023). 

According to the prescribing information, Aphexda is contraindicated in individuals who have a history of serious hypersensitivity reactions to Aphexda.

Per the prescribing information, Aphexda carries the following warnings and precautions:

  • Anaphylactic shock and hypersensitivity reactions: Premedicate all patients with a combination of an H1-antihistamine, an H2 blocker, and a leukotriene inhibitor prior to each Aphexda dose. Administer Aphexda in a setting where personnel and therapies are available for immediate treatment. Observe for signs and symptoms and manage promptly.
  • Injection site reactions: The addition of analgesic premedication (e.g., acetaminophen) is recommended.
  • Tumor cell mobilization in patients with leukemia: Aphexda may mobilize leukemic cells and should not be used in leukemia patients.
  • Leukocytosis: Increased circulating leukocytes have been observed. Monitor white blood cell counts during Aphexda use.
  • Potential for tumor cell mobilization: Tumor cells may be released from marrow during hematopoietic stem cell (HSC) mobilization with Aphexda and filgrastim. Effect of reinfusion of tumor cells is unknown.
  • Embryo-fetal toxicity: Can cause fetal harm. Advise women of reproductive potential of the potential risk to a fetus and to use effective contraception.

Per the prescribing information, the most common adverse reactions (≥ 20%) include: injection site reactions, injection site pain, injection site erythema, injection site pruritis, pruritis, flushing, and back pain.

On September 11, 2023, the U.S. Food and Drug Administration (FDA) approved motixafortide (Aphexda) in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous stem cell transplant (ASCT) in patients with multiple myeloma. The FDA approval was based on supporting data from the GENESIS study (BioLineRx, 2023).

In the GENESIS study, a randomized, double-blind, placebo-controlled, multicenter, 2-part phase 3 trial, Crees and colleagues (2023) evaluated the safety and efficacy of Aphexda plus filgrastim, compared to placebo plus filgrastim, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. One hundred and twenty-two patients with multiple myeloma were randomized 2:1 to receive Aphexda 1.25 mg/kg subcutaneously (n = 80) or placebo (n = 42). Prior to receipt of Aphexda or placebo, patients received daily morning doses of filgrastim 10-15 mcg/kg for 4 days. Aphexda or placebo was administered on the evening of Day 4. Patients received a fifth morning dose of filgrastim within 1 hour prior to their first apheresis (12 hours ± 2 hours from the Aphexda/placebo administration) on Day 5. The primary endpoint for the study was an apheresis cell collection goal ≥ 6 x 106 CD34+ cells/kg within two apheresis procedures after administration of filgrastim and a single administration of Aphexda or placebo. The secondary endpoint was to achieve this goal in one apheresis. Efficacy results demonstrated that 67.5% of patients in the Aphexda treatment arm versus 9.5% in the placebo arm achieved a collection goal of ≥ 6 x 106 CD34+ cells/kg in up to 2 aphereses following a single administration of Aphexda or placebo, resulting in an adjusted difference between treatment arms of 56.8% (p<0.0001). Aphexda plus filgrastim was safe and well tolerated. The most common treatment-related adverse events were transient grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). The investigators concluded that Aphexda plus filgrastim produced a significantly greater mobilization of CD34+ hematopoietic stem cell numbers within 2 apheresis procedures versus placebo plus filgrastim while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive hematopoietic stem cells.


References

The above policy is based on the following references:

  1. BioLine Rx Ltd. BioLineRx announces FDA approval of Aphexda (motixafortide) in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells for collection and subsequent autologous transplantation in patients with multiple myeloma. Press Release. Tel Aviv, Israel: BioLineRx; September 11, 2023.
  2. BioLineRx USA Inc. Aphexda (motixafortide) for injection, for subcutaneous use. Prescribing Information. Waltham, MA: BioLineRx USA; revised September 2023.
  3. Crees ZD, Rettig MP, Jayasinghe RG, et al. Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: A randomized phase 3 trial. Nat Med. 2023;29(4):869-879.