Axatilimab-csfr (Niktimvo)

Number: 1069

Table Of Contents

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

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses axatilimab-csfr (Niktimvo) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of axatilimab-csfr (Niktimvo) is required of all Aetna participating providers and members in applicable plan designs. For precertification of axatilimab-csfr (Niktimvo), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

1. Criteria for Initial Approval

   Aetna considers axatilimab-csfr (Niktimvo) medically necessary for the treatment of chronic graft-versus-host disease (cGVHD) when both of the following criteria are met:

   1. The member has had at least two prior lines of systemic therapy that failed to produce the desired response; and
   2. The member weighs at least 40 kg.

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

2. Continuation of Therapy

   Aetna considers continuation of axatilimab-csfr (Niktimvo) therapy medically necessary for members requesting reauthorization for an indication listed in the Criteria for Approval section when there is no evidence of unacceptable toxicity or disease progression while on the current regimen. 

3. Related Policies 

   1. CPB 0024 - Aldesleukin (Proleukin)
   2. CPB 0241 - Extracorporeal Photochemotherapy (Photopheresis)
   3. CPB 0314 - Rituximab
   4. CPB 0315 - Etanercept
   5. CPB 0720 - Abatacept (Orencia)

Dosage and Administration

Axatilimab-csfr is available as Niktimvo and supplied in following dosage forms and strengths for intravenous use:

• 9 mg/0.18 mL solution in a single-dose vial
• 22 mg/0.44 mL solution in a single-dose vial
• 50 mg/mL solution in a single-dose vial.

For persons weighing at least 40 kg, the recommended dosage is 0.3 mg/kg (up to a maximum dose of 35 mg) as an intravenous infusion over 30 minutes every 2 weeks until progression or unacceptable toxicity. 

Source: Incyte Corporation, 2025

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96413	Chemotherapy administration, IV infusion technique; up to 1 hour, single or initial substance/drug
96415	each additional hour (list in addition to code for primary procedure)
HCPCS codes covered if selection criteria are met:
J9038	Injection, axatilimab-csfr, 0.1 mg
ICD-10 codes covered if selection criteria are met:
D89.811	Chronic graft-versus-host disease

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Background

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

• Niktimvo is indicated for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg.

Compendial Use

• Chronic graft-versus-host disease (GVHD)

Axatilimab-csfr, a colony stimulating factor-1 receptor (CSF-1R)-blocking antibody, is branded as Niktimvo (Incyte Corporation). Specifically, axatilimab-csfr is a humanized IgG4 (kappa light chain) monoclonal antibody that targets CSF-1R expressed on monocytes and macrophages. Blocking CSF-1R has been shown to reduce the levels of circulating proinflammatory and profibrotic monocytes and monocyte-derived macrophages and inhibit the activity of pathogenic macrophages in tissues. Macrophages dependent on CSF-1R have been implicated in the development and worsening of chronic graft-versus-host disease (cGVHD). Axatilimab-csfr has been found to inhibit CSF-1R signaling and impede macrophage development, thereby reducing symptom burden in patients with cGVHD.

Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (cGVHD) is a serious multisystem syndrome that can occur after an allogeneic hematopoietic stem cell transplant (HSCT). It is caused when donor cells initiate an immune response and attack the transplant recipient’s cells and tissues. Chronic GVHD is estimated to develop in approximately 42% of transplant recipients, affecting approximately 17,000 patients in the United States. 

The onset of cGVHD usually begins between 3 months and 1-2 years after transplantation; however, some cases may present earlier or later than this timeline. There is a distinction between acute GVHD (aGVHD) and cGVHD, which used to be based on the time of onset from transplantation. Acute versus chronic GVHD is now defined by their clinical and/or pathologic features, as both conditions can occur outside of those time periods. cGVHD can arise de novo (i.e., in a patient with no prior GVHD), referred to as classic cGVHD. It can also arise in a patient with ongoing or prior aGVHD, referred as overlap syndrome.

Clinical features of cGVHD can involve nearly every organ system; however, the skin (resembling lichen planus or cutaneous manifestations of scleroderma), liver, gastrointestinal (GI) tract, and lungs (bronchiolitis obliterans) are the primary organ systems involved. A biopsy is often valuable for diagnosis, but it is not always feasible and is not required for patients who have National Institutes of Health (NIH)-defined diagnostic clinical features of cGVHD.

Medication management is guided by the involved organs, severity of findings, and response to treatment. First-line treatment consists of corticosteroids. Steroid-refractory treatment may include calcineurin inhibitors (CNIs), a selective Janus kinase (JAK) inhibitor (ruxolitinib), Bruton tyrosine kinase inhibitor (ibrutinib), ROCK2 (Rho-associated coiled-coil–containing protein kinase 2) inhibitor (belumosudil), or other immunosuppressants (e.g., mycophenolate mofetil, sirolimus, azathioprine).

In August 2024, the FDA approved axatilimab-csfr (Niktimvo) for the treatment of cGVHD after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg. FDA approval was based on the efficacy and safety data from a randomized, open-label, multicenter, dose-ranging phase 2 trial (AGAVE-201; NCT04710576) which met the primary endpoint of overall response rate (ORR) across all cohorts receiving axatilimab-csfr.

The AGAVE-201 trial investigated 3 dosages of axatilimab-csfr in 241 adult and pediatric patients with recurrent or refractory cGVHD who had received at least 2 lines of systemic therapy and required additional treatment. Patients were randomized to one of three treatment groups that investigated a distinct dose of axatilimab administered at 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks or 3.0 mg/kg every four weeks. The trial's primary endpoint was the proportion of patients in each dose group who achieved an objective response as defined by 2014 NIH Consensus Criteria for cGVHD by cycle 7 day 1. Secondary endpoints included duration of response, percent reduction in daily steroids dose, organ specific response rates and validated quality-of-life assessments using the modified Lee Symptom Scale. Patients received axatilimab-csfr intravenously until disease progression, lack of efficacy by 9 months, or unacceptable toxicity. The study found that among patients who received 0.3 mg/kg every 2 weeks (N=79), ORR was 75% (95% CI, 64-84), with all responders having a partial response. Median time to first response was 1.5 months (range, 0.9-5.1) and median duration of response was 1.9 months (95% CI, 1.6-3.5). Among patients who achieved response, 60% (95% CI, 43-74) maintained a response at 12 months. Additionally, 56% (95% CI, 44-67) of patients achieved at least a 7-point improvement in the modified Lee Symptom Scale score. Organ specific responses were observed across all organs involved at baseline, with notable responses in fibrosis-dominated organs, such as the esophagus, joints and fascia, lungs, and skin.

Infusion-related reactions, including hypersensitivity reactions, occurred in 18% of patients who received axatilimab-csfr in the clinical trial, with Grade 3 or 4 reactions in 1.3%.

Based on its mechanism of action, axatilimab-csfr may cause fetal harm when administered to a pregnant woman. Moreover, for lactating women, breastfeeding is not advised.

The most common (15% or more) adverse reactions, including laboratory abnormalities, were increased aspartate aminotransferase (AST), infection (pathogen unspecified), increased alanine aminotransferase (ALT), decreased phosphate, decreased hemoglobin, viral infection, increased gamma glutamyl transferase (GGT), musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase (CPK), increased alkaline phosphatase (ALP), nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea.

The National Comprehensive Cancer Network Drugs & Biologics Compendium provides a category 2A recommendation for the use of axatilimab-csfr in conjunction with systemic corticosteroids following failure (steroid-refractory disease) to at least two prior lines of systemic therapy in patients with chronic GVHD who are greater than or equal to 40 kg (NCCN, 2025).

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References