Commercial

Medical Policy

Title:

Axatilimab-csfr (Niktimvo™) for Intravenous Use

Policy #:

08.02.34

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member's medical needs and condition.

MEDICALLY NECESSARY

Axatilimab-csfr (Niktimvo^TM), administered via an intravenous (IV) route, is considered medically necessary and, therefore, covered for the treatment of chronic graft-versus-host disease (cGVHD) in adults and pediatric individuals weighing at least 40 kg when ALL of the following are met:

The individual has a documented diagnosis of chronic graft-versus-host disease
Failure (steroid-refractory disease) of at least two prior lines of systemic therapy
Used as additional therapy in conjunction with systemic corticosteroids

EXPERIMENTAL/INVESTIGATIONAL

All other uses for axatilimab-csfr (Niktimvo) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, axatilimab-csfr (Niktimvo) is covered under the medical benefits of the Company's products when the medical necessity criteria listed in this medical policy are met.

NATIONAL INSTITUTES OF HEALTH CHRONIC GRAFT-VERSUS-HOST DISEASE CRITERIA

The National Institutes of Health (NIH) has developed criteria for diagnosing and classifying chronic graft-versus-host disease (cGVHD). Diagnosing cGVHD is complex and requires looking at a histological examination of tissue, laboratory results, and also a complete examination of the individual. Shulman et al. (2015) include in-depth details of the histological findings with cGVHD, by organ system, in their discussion of the NIH criteria. In addition to discussing the histological criteria, Jagasia et al. (2015) discuss the physical examination findings that could result in a diagnosis of cGVHD in their discussion of the NIH criteria.

US FOOD AND DRUG ADMINISTRATION STATUS

The US Food and Drug Administration (FDA) approved axatilimab-csfr (Niktimvo) on August 14, 2024, for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adults and pediatric individuals weighing at least 40 kg.

PEDIATRIC USE

The safety and effectiveness of axatilimab-csfr (Niktimvo) in pediatric individuals weighing less than 40 kg have not been established.

Description

CHRONIC GRAFT-VERSUS-HOST DISEASE

A hematopoietic cell transplantation (HCT) can be used as a treatment for hematological disorders such as lymphoma, leukemia, or bone marrow failure. Immune cells in the donated transplanted material (graft) can view the recipient as a foreign body and attack the recipient's immune system (host) resulting in graft-versus-host disease (GVHD). GVHD can be classified as either being acute, chronic, or both (overlap syndrome). Acute GVHD (aGVHD) usually occurs within the first 3 months after the HCT, but may also start later, and is often milder in severity. The usually affected organs include the skin, gastrointestinal (GI) tract, and the liver. Chronic GVHD (cGVHD) usually occurs more than 3 months after the HCT, but may start sooner as well, and is often more severe in nature. The list of organs that can be affected include the skin, GI tract, and liver, but also can include the mouth, lungs, muscles, joints, and genitals. The incidence of developing cGVHD is approximately 40 percent after the HCT. There are multiple risk factors associated with the development of cGVHD that can include HLA mismatch, older age of either the donor and/or the recipient, mismatched sex of the donor and recipient, a donor who has previously been pregnant, the source of the graft (bone marrow or umbilical cord blood pose less risk than peripheral blood precursor cells), splenectomy, previously experiencing aGVHD, and the presence of cytomegalovirus (CMV) or Epstein-Barr virus (EBV) seropositivity. The risk of developing cGVHD increases with the number of risk factors present in the host individual. The diagnosis of cGVHD is usually made on the basis of the results of a physical examination, laboratory tests, and tissue biopsy. To prevent GVHD, immunosuppressive agents, or other medications (e.g., cyclophosphamide, anti–T-lymphocyte globulin), are ordered as prophylaxis. If the cGVHD is mild, localized or topical treatments can be used. Corticosteroids are the first systemic treatment ordered if the mild cGVHD is widespread, or at the time of moderate or severe cGVHD onset. If those treatments are unsuccessful at keeping cGVHD in check, there are other medications that can be ordered (e.g., ruxolitinib, belumosudil, ibrutinib) or extracorporeal photopheresis can be used.

AXATILIMAB-CSFR (NIKTIMVO)

Axatilimab-csfr (Niktimvo) is a humanized immunoglobulin 4 (IgG4; kappa light chain) monoclonal antibody that acts as a colony stimulating factor-1 receptor (CSF-1R)–blocking agent. Axatilimab-csfr (Niktimvo) binds to CSF-1Rs expressed on monocytes and macrophages, resulting in reduced levels of the circulating proinflammatory and profibrotic monocytes and monocyte-derived macrophages, which inhibits their activity in tissues.

CLINICAL TRIAL INFORMATION

The efficacy and safety of axatilimab-csfr (Niktimvo) was evaluated in a randomized, open-label, multicenter phase II study (NCT04710576) that included adult and pediatric individuals with recurrent or refractory cGVHD who had received at least two prior lines of systemic treatment. A total of 241 individuals were enrolled and randomly assigned 1:1:1 into three cohorts. Cohort 1 received a dose of 0.3 mg/kg intravenously (IV) every 2 weeks. Cohort 2 received a dose of 1 mg/kg IV every 2 weeks. Cohort 3 received 3 mg/kg IV every 4 weeks. Treatment continued until the occurrence of cGVHD progression, unacceptable toxicity, lack of a response by 9 months of treatment, or withdrawal of consent. The primary endpoint was an overall response rate (ORR; included complete or partial responses) that exceeded 30 percent of individuals before the beginning of cycle 7 of treatment. A key secondary endpoint included the number of participants with a clinically significant improvement in normalized score (reduction of more than 5 points) on the modified Lee Symptom Scale, along with safety measures.

All three cohorts achieved the primary endpoint. The ORR for Cohort 1 was 74 percent, for Cohort 2 was 67 percent, and for Cohort 3 was 50 percent. Of the individuals who experienced a response, 60 percent in Cohort 1, 60 percent in Cohort 2, and 53 percent in Cohort 3 had a durable response at 12 months. The percentage of individuals who achieved a clinically significant improvement on the modified Lee Symptom Scale was 60 percent, 69 percent, and 41 percent, respectively, in Cohorts 1, 2, and 3. The percentage of individuals who experienced a Grade 3 or greater adverse event was 49, 60, and 71 in Cohorts 1, 2, and 3, respectively. The most common adverse events were transient laboratory abnormalities. Adverse events leading to the discontinuation of treatment occurred in 6 percent, 22 percent, and 18 percent of individuals in Cohorts 1, 2, and 3, respectively. Fatal adverse events occurred in 1 percent, 9 percent, and 8 percent of individuals in Cohorts 1, 2, and 3, respectively. Based on these results, a dosage of 0.3 mg/kg every 2 weeks was determined to be the safest and efficacious dosage for treatment.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Hospital Formulary Service (AHFS). Axatilimab-csfr (Niktimvo^TM). AHFS Drug Information. [UpToDate Lexidrug Web site]. 01/21/2026. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed February 24, 2026.

Cleveland Clinic. Graft vs. host disease. [Cleveland Clinic Web site]. 02/21/2023. Available at: https://my.clevelandclinic.org/health/diseases/10255-graft-vs-host-disease-an-overview-in-bone-marrow-transplant. Accessed February 24, 2026.

ClinicalTrials.gov. A study of axatilimab at 3 different doses in participants with chronic graft versus host disease (cGVHD) (AGAVE-201). ClinicalTrials.gov Identifier: NCT04710576. First Posted: January 14, 2021. Last Update Posted: September 3, 2025. Available at: https://clinicaltrials.gov/. Accessed February 24, 2026.

Elsevier's Clinical Pharmacology Compendium. Axatilimab-csfr (Niktimvo^TM). [Clinical Key Web site]. 08/06/2025. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed February 24, 2026.

Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. the 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.

Merative Micromedex^® DRUGDEX^® (electronic version). Axatilimab-csfr (Niktimvo^TM). [Micromedex Web site]. 07/29/2025. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed February 24, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^®. Hematopoietic Cell Transplantation, V3.2025. [NCCN Web site]. 09/24/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/hct.pdf. [via subscription only]. Accessed February 24, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium^®. [NCCN Web site]. Axatilimab-csfr (Niktimvo^TM). Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed February 24, 2026.

Penack O, Marchetti M, Ruutu T, et al. Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol. 2020;7(2):e157-e167.

Shulman HM, Cardona DM, Greenson JK, et al. NIH Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: the 2014 Pathology Working Group report. Biol Blood Marrow Transplant. 2015;(4):589-603.

UpToDate^® Lexidrug^TM. Axatilimab-csfr (Niktimvo^TM). [UpToDate Lexidrug Web site]. 01/02/2026. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed February 24, 2026.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Axatilimab-csfr (Niktimvo^TM). Prescribing information. [FDA Web site]. 08/14/2024. Available at https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed February 24, 2026.

Wolff D, Cutler C, Lee SJ, et al. Axatilimab in recurrent or refractory chronic graft-versus-host disease. N Engl J Med. 2024;391(11):1002-1014.

Zeiser R. Clinical manifestations and diagnosis of chronic graft-versus-host disease. [UpToDate Web site]. 02/27/2024. Available at: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-graft-versus-host-disease?search=chronic graft vs host disease&source=search_result&selectedTitle=1~134&usage_type=default&display_rank=1 [via subscription only]. Accessed February 24, 2026.

Zeiser R. Treatment of chronic graft-versus-host disease. [UpToDate Web site]. 09/25/2024. Available at: https://www.uptodate.com/contents/treatment-of-chronic-graft-versus-host-disease?search=chronic graft vs host disease&source=search_result&selectedTitle=2~134&usage_type=default&display_rank=2 [via subscription only]. Accessed February 24, 2026.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)

J9038 Injection, axatilimab-csfr, 0.1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

New Policy 08.02.34:

04/01/2026	The policy has been reviewed and reissued to communicate the Company’s continuing position on axatilimab-csfr (Niktimvo^TM) for intravenous use.
07/28/2025	This policy will become effective 07/28/2025. The following new policy has been developed to communicate the Company's coverage criteria for axatilimab-csfr (Niktimvo^TM) for intravenous use.

Version Effective Date:

7/28/2025

Version Issued Date: