Effective Date

Date of Origin   

10-01-2025           

07-01-2024

FABHALTA®

(iptacopan)

Capsule

Treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH)

Reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) greater than or equal to 1.5 g/g

Treatment of adults with complement 3 glomerulopathy (C3G), to reduce proteinuria

1

Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, life-threatening, rare, multi-systemic disease developing as a result of a somatic mutation of hematopoietic stem cells, and characterized by clonal, complement-mediated intravascular hemolysis. PNH is mainly a disease of adults with a median age of onset in the thirties. High precision flow cytometry is the most useful and accepted diagnostic test to confirm the diagnosis of PNH. Flow cytometry is performed by incubating the patient’s peripheral blood cells with fluorescently-labeled monoclonal antibodies that bind to glycosylphosphatidylinositol (GPI) anchored proteins, which are reduced or absent on blood cells in PNH. Since different blood cell lineages display different combinations of GPI-linked proteins, and some proteins bind to cell surfaces via both GPI-linked and GPI-independent mechanisms, it is recommended that at least two independent flow cytometry reagents be used on at least two cell lineages (e.g., red blood cells [RBCs] and white blood cells [WBCs]) to establish a diagnosis of PNH.(2)

The lack of the complement inhibitor CD59 on RBCs surface is mostly responsible for the clinical manifestations in PNH. These patients manifest with chronic intravascular hemolysis, paroxysmal flares of hemolysis, and a propensity for thrombosis. Intravascular hemolysis leads to release of free hemoglobin (Hb) into the blood. Free Hb, in turn, can cause various toxic effects, including hypercoagulability, changes in vascular tone from reduction of circulating nitric oxide, and renal damage.(3)

Extravascular hemolysis also occurs in patients with PNH because C3 fragments that are not destroyed by the membrane attack complex (MAC) intravascularly can accumulate on the GPI-negative RBCs (lacking CD55) surface and these fragments opsonize the RBCs, causing reticuloendothelial destruction in the liver and spleen.(3)

The main clinical situations or diseases that should be considered in the differential diagnosis of PNH are:(3)

• Coombs-negative hemolytic anemia (e.g., hemoglobinopathies, hereditary spherocytosis), microangiopathic hemolytic anemias, drug- or toxin-induced hemolysis/anemias, disseminated intravascular coagulation, and autoimmune hemolysis
• Venous thrombosis in atypical sites, including myeloproliferative disorders; solid tumors associated with hypercoagulability; extrinsic compression of vessels, and; inherited/acquired thrombophilias
• Anemia and/or other cytopenias related to bone marrow failure syndrome (e.g., aplastic anemia, myelodysplastic syndrome [MDS])

PNH is classified into three different categories:(3)

• Classic PNH (PNH with clinical and laboratory findings of intravascular hemolysis without any evidence of bone marrow deficiency)
• PNH in the setting of another specified bone marrow disorder (evidence of hemolysis, as well as another specified bone marrow disorder [e.g., aplastic anemia, MDS])
• Subclinical PNH (patients with a small population of PNH cells and no clinical or laboratory evidence of hemolysis or thrombosis)

Historically, patients with PNH had a median survival of ten years after diagnosis however, since the development of complement inhibitors survival rates have improved to approximately 75%.(4) The approach to therapy depends on the severity of symptoms and the degree of hemolysis. The treatment options for PNH are supportive care, allogenic hematopoietic stem cell transplantation (HSCT), and a complement blockade.(2,3)

Immunoglobulin A Nephropathy

Immunoglobulin A nephropathy (IgAN), also known as Berger’s disease, is a kidney disease that occurs when IgA deposits build up in the kidneys, causing inflammation that damages the glomeruli, in turn causing the kidneys to leak blood and protein into the urine. The damage may lead to scarring of the nephrons that progresses slowly over many years. Eventually, IgAN can lead to end-stage renal disease (ESRD).(11)

Kidney biopsy is required to confirm the diagnosis of IgAN as there are no validated diagnostic serum or urine biomarkers for IgAN. Biopsy is indicated when a patient has signs of severe or progressive disease. After a diagnosis has been established, guidelines recommend that all patients with IgAN be assessed for secondary causes (e.g., liver cirrhosis, HIV, hepatitis, inflammatory bowel disease).(11)

The primary focus of IgAN management should be optimized supportive care (e.g., blood pressure management, maximally tolerated angiotensin-converting-enzyme inhibitor [ACEi] or angiotensin II blocker [ARB], lifestyle modification, address cardiovascular risk). Guidelines recommend that all patients with proteinuria greater than 0.5 g/d be treated with an ACEi or ARB irrespective of whether they have hypertension.(11) Recent literature also supports the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a component of maximal supportive care.(10,11) Furthermore, recent guidelines recommend simultaneous commencement of disease-modifying therapy and therapies to manage the consequences of IgAN-induced nephron loss.(11)

Guidelines define a patient with IgAN at risk of progressive loss of kidney function if they have a proteinuria greater than or equal to 0.5 g/d (or equivalent).(11) Proteinuria of 0.5 g/d is approximately equivalent to a urine protein to creatinine ratio (UPCR) of 0.44 g/g.(9) Systemic glucocorticoids have no proven impact on levels of pathogenic forms of IgA or IgA immune complexes and are used to manage glomerular inflammation. However, Tarpeyo (Nefecon) is recommended in the 2024 KDIGO guidelines as efficacy data supports a reduction in pathogenic IgA and IgA immune complexes.(11) The American Journal of Kidney Disease (AJKD) recommends corticosteroids (targeted release budesonide, Nefecon, or reduced dose corticosteroids) for high-risk patients with inflammatory lesions seen on kidney biopsy.(10) Most literature supports some use of corticosteroids as part of a treatment regimen; however, the dose and duration is questionable.(10,11) Furthermore, long-term outcomes-based comparative studies for corticosteroids in the IgAN setting is lacking and future studies are needed to determine any clinical significance. It is further noted that the following patient characteristics are likely to increase the risks of systemic glucocorticoid toxicity:(11)

• eGFR less than 30 mL/min/1.73 m^2
• Diabetes and prediabetes
• Obesity
• Latent infections (e.g., viral hepatitis, tuberculosis)
• Active peptic ulceration
• Uncontrolled psychiatric illness
• Osteoporosis
• Cataracts

The goal of treatment in patients with IgAN at risk of progressive loss of kidney function is to reduce the rate of loss of kidney function to less than 1 mL/min per year for the rest of the patient's life. An additional treatment goal is the reduction of proteinuria to less than 0.5 g/d (or equivalent).(11)

Complement 3 Glomerulopathy

Complement 3 glomerulopathy (C3G) is a progressive and ultra-rare (5 cases per 1,000,000 in the United States) kidney disease that is characterized by dysregulation of the alternative complement pathway.(7) The disease can be divided into two major subgroups, dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). While these two subgroups have unique characteristics that can be differentiated with a kidney biopsy and electron microscopy, they both cause excessive activation of the alternative complement pathway.(6) It is estimated that within 10 years of diagnosis, almost 50% of patients with C3G will progress to end-stage kidney disease.(8) The clinical presentation of C3G can be highly variable. Most patients will present with proteinuria and/or hematuria, hypertension, complement abnormalities (low serum C3 levels), and kidney function decline. The onset of disease can also be variable affecting both pediatric and adult patients. The mean age at diagnosis is 9 and 39 years.(8) Kidney biopsy is required to confirm the diagnosis of C3G.(5) Guidelines recommend treating patients with C3G who have proteinuria greater than 1 g/d.(5) Proteinuria of 1 g/d is approximately equivalent to a urine protein to creatinine ratio (UPCR) of 0.88 g/g.(9) Historically, treatment options for C3G have been limited and have focused more on supportive measures (e.g., blood pressure management, lifestyle modification, diet). Therapeutic decisions are driven by disease severity and several off-label therapies have shown mixed results.(6) Most experts recommend renin angiotensin system inhibitor (RASi) therapy, and in some patients immunosuppressants are used as first-line agents. Furthermore, the recommendation to use immunosuppressants (corticosteroids and mycophenolate based regimens) is largely based on a few retrospective studies and well controlled studies are unavailable.(5,6,8)

Efficacy

FABHALTA binds to Factor B of the alternative complement pathway and regulates the cleavage of C3, generation of downstream effectors, and the amplification of the terminal pathway. In PNH, intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex, while extravascular hemolysis (EVH) is facilitated by C3b opsonization. FABHALTA acts proximally in the alternative pathway of the complement cascade to control both C3b-mediated EVH and terminal complement mediated IVH.(1)

The efficacy of FABHALTA in adults with PNH was evaluated in a multi-center, open-label, 24-week active comparator-controlled trial (APPLY-PNH; NCT04558918). The study enrolled adults with PNH and residual anemia (Hb < 10 g/dL) despite previous treatment with a stable regimen of anti-C5 treatment (either eculizumab or ravulizumab) for at least 6 months prior to randomization. Efficacy primary endpoints were established based on demonstration of superiority of switching to FABHALTA compared to continuing on anti-C5 therapy in achieving hematological response after 24 weeks of treatment, without a need for transfusion, by assessing the proportion of patients demonstrating:(1)

• Sustained increase of greater than or equal to 2 g/dL in Hb levels from baseline (Hb improvement) 
• Sustained hemoglobin levels greater than or equal to 12 g/dL

Secondary endpoints included:(1)

• Transfusion avoidance
• Change from baseline in Hb levels
• Change from baseline in absolute reticulocyte counts

Patients with sustained increase of Hb levels greater than or equal to 2 g/dL in the FABHALTA arm had an 82.3% response rate (95% CI) and the response rate in the Anti-C5 arm was 0%. Patients with sustained Hb level greater than or equal to 12 g/dL in the absence of transfusions in the FABHALTA arm had a 67.7% response rate (95% CI) and the response rate in the Anti-C5 arm was 0%.(1)  

FABHALTA was studied in a single arm study in adults with PNH who were not previously treated with a complement inhibitor (APPOINT-PNH; NCT04820530). Adult patients with PNH (RBC clone size greater than or equal to 10%), Hb less than 10 g/dL, and LDH greater than 1.5 times the upper limit of normal received FABHALTA during the 24-week open-label core treatment period. In total, 77.5% (95% CI: 61.5%, 89.2%) of patients achieved a sustained increase (between Day 126 and Day 168) in Hb levels from baseline of greater than or equal to 2 g/dL in the absence of RBC transfusions.(1)

Additionally, the effect of FABHALTA was evaluated in a multicenter, randomized, double-blind study (APPLAUSE-IgAN, NCT04578834) in adults with biopsy-proven IgAN, eGFR greater than or equal to 20 mL/min/1.73 m^2, and urine protein-to-creatinine ratio (UPCR) greater than or equal to 1 g/g on a stable (12-week) dose of maximally-tolerated renin-angiotensin system (RAS) inhibitor therapy with or without a stable (12-week) dose of an SGLT2 inhibitor. Patients were randomized (1:1) to either FABHALTA 200 mg or placebo twice daily. Rescue immunosuppressive treatment could be initiated per investigator discretion during the trial. The efficacy analysis was based on the first 250 patients with an eGFR greater than or equal to 30 mL/min/1.73 m^2 (Main Study Population), who had completed or discontinued the study prior to the Month 9 visit. The primary endpoint was the percent reduction in UPCR (sampled from a 24-hr urine collection) at Month 9 relative to baseline. The FABHALTA treatment arm showed a 44% (95% CI; 36%, 51%) reduction in UPCR while the placebo treatment arm showed a 9% (95% CI; -5%, 21%) reduction in UPCR from baseline at month 9.(1)

The efficacy of FABHALTA in reducing proteinuria in adult patients with native kidney C3G was demonstrated in a randomized, double-blind, placebo-controlled study in 74 patients with biopsy confirmed disease (APPEAR-C3G; NCT04817618). The study enrolled adult patients who had a UPCR greater than or equal to 1 g/g and eGFR greater than or equal to 30 mL/min/1.73 m^2. Patients were required to be on a maximally tolerated RAS inhibitor and could be on a corticosteroid and/or mycophenolate mofetil/sodium (MMF/MPS) at baseline. All background therapies (i.e., RAS inhibitors, corticosteroids and MMF/MPS) were required to be at stable doses for 90 days prior to randomization and throughout the study. Patients were randomized (1:1) to receive either FABHALTA 200 mg orally twice daily (N = 38) or placebo (N = 36) for 6 months, followed by a 6-month open-label treatment period in which all patients received FABHALTA 200 mg orally twice daily. The primary efficacy endpoint was the log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) at 6 months. At 6 months, the geometric mean UPCR ratio relative to baseline was 0.70 (95% CI: 0.57, 0.85) and 1.08 (95% CI: 0.88, 1.31) in the FABHALTA and placebo groups, respectively, resulting in a 35% reduction in 24-hour UPCR from baseline in the FABHALTA group compared to placebo (p = 0.0028).(1)

Safety

FABHALTA has the following boxed warnings:(1)

FABHALTA increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. Life-threatening and fatal infections have occurred and these infections may become rapidly life-threatening or fatal if not recognized and treated early.

• Vaccinate patients against encapsulated bacteria as recommended at least 2 weeks prior to administering the first dose of FABHALTA, unless the risks of delaying therapy with FABHALTA outweigh the risk of developing a serious infection
• Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria
• Patients receiving FABHALTA are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected

​​​​FABHALTA is contraindicated in the following:(1)

• Serious hypersensitivity to iptacopan or any of the excipients
• Initiation in patients with unresolved serious infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type B

FABHALTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called FABHALTA REMS.(1)

1

FABHALTA prescribing information. Novartis Pharmaceuticals Corporation. March 2025.

2

Sahin Fahri, MeltemF, Akay OOM, Ayer M, et al. Pesg PNH diagnosis, follow-up and treatment guidelines. Am J Blood Res. PubMed Central (PMC). Published 2016; 6(2): 19-27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981648/

3

Cançado RD, Da Silva Araújo A, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematology, Transfusion and Cell Therapy. 2021;43(3):341-348. doi:10.1016/j.htct.2020.06.006

4

Shah N, Bhatt H. Paroxysmal nocturnal hemoglobinuria. StatPearls - NCBI Bookshelf. Published July 31, 2023. https://www.ncbi.nlm.nih.gov/books/NBK562292/

5

Rovin BH, Adler SG, Barratt J, et al. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney International. 2021;100(4):S1-S276. doi:10.1016/j.kint.2021.05.021.

6

Smith RJH, Appel GB, Blom AM, et al. C3 glomerulopathy — understanding a rare complement-driven renal disease. Nature Reviews Nephrology. 2019;15(3):129-143. doi:10.1038/s41581-018-0107-2

7

Cattran DC, Sethi S. Slowly unraveling the mysteries of C3G. American Journal of Kidney Diseases. 2021;77(5):670-672. doi:10.1053/j.ajkd.2020.12.009

8

Magliulo EK, Ravipati P. C3 Glomerulopathy: A Current perspective in an evolving landscape. Glomerular Diseases. 2024;4(1):200-210. doi:10.1159/000542354

9

Pitcher D, Braddon F, Hendry B, et al. Long-Term outcomes in IGA nephropathy. Clinical Journal of the American Society of Nephrology. 2023;18(6):727-738. doi:10.2215/cjn.0000000000000135

10

Caster DJ, Lafayette RA. The treatment of primary IGA nephropathy: Change, change, change. American Journal of Kidney Diseases. 2023;83(2):229-240. doi:10.1053/j.ajkd.2023.08.007

11

KDIGO 2024 CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF IMMUNOGLOBULIN A NEPHROPATHY (IgAN) AND IMMUNOGLOBULIN A VASCULITIS (IgAV); 2024. https://kdigo.org/wp-content/uploads/2024/08/KDIGO-2024-IgAN-IgAV-Guideline-Public-Review-Draft.pdf.

Fabhalta

iptacopan hcl cap

200 MG

M ; N ; O ; Y

N

Fabhalta

iptacopan 200 mg capsules

200 MG

60

Capsules

30

DAYS

Fabhalta

iptacopan hcl cap

200 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

Fabhalta

iptacopan 200 mg capsules

200 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The patient has a diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH) as confirmed by flow cytometry with at least 2 independent flow cytometry reagents on at least 2 cell lineages (e.g., RBCs and WBCs) demonstrating that the patient’s peripheral blood cells are deficient in glycosylphosphatidylinositol (GPI) – linked proteins (lab tests required) OR
   2. The patient has a diagnosis of primary immunoglobulin A nephropathy (IgAN) confirmed by kidney biopsy AND ALL of the following:
      1. ONE of the following:
         1. The patient has a urine protein-to-creatinine ratio (UPCR) greater than or equal to 0.44 g/g OR
         2. The patient has proteinuria greater than or equal to 0.5 g/day AND
      2. The patient’s eGFR is greater than or equal to 30 mL/min/1.73 m^2 AND
      3. The patient has ONE of the following:
         1. Tried and had an inadequate response after at least a 3-month duration of therapy with a maximally tolerated angiotensin-converting-enzyme inhibitor (ACEi, e.g., benazepril, lisinopril) or angiotensin II blocker (ARB, e.g., losartan), or a combination medication containing an ACEi or ARB OR
         2. An intolerance or hypersensitivity to an ACEi or ARB, or a combination medication containing an ACEi or ARB OR
         3. An FDA labeled contraindication to ALL ACEi and ARB OR
   3. The patient has a diagnosis of complement 3 glomerulopathy (C3G) confirmed by kidney biopsy AND ALL of the following:
      1. ONE of the following:
         1. The patient has a urine protein-to-creatinine ratio (UPCR) greater than 0.88 g/g OR
         2. The patient has proteinuria greater than 1.0 g/day AND
      2. The patient’s eGFR is greater than or equal to 30 mL/min/1.73 m^2 AND
      3. ONE of the following:
         1. BOTH of the following:
            1. The patient is currently treated with a maximally tolerated angiotensin-converting-enzyme inhibitor (ACEi, e.g., benazepril, lisinopril) or angiotensin II blocker (ARB, e.g., losartan), or a combination medication containing an ACEi or ARB for at least a 90-day duration of therapy AND
            2. The patient will continue maximally tolerated ACEi, or ARB, or a combination medication containing an ACEi or ARB therapy in combination with the requested agent OR
         2. The patient has an intolerance, hypersensitivity, or FDA labeled contraindication to ALL ACEi, ARB, and combination medications containing an ACEi or ARB OR
   4. The patient has another FDA labeled indication for the requested agent and route of administration AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., hematologist, nephrologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient will NOT be using the requested agent in combination with Empaveli (pegcetacoplan), Soliris (eculizumab), Bkemv (eculizumab-aeeb), Epysqli (eculizumab-aagh), Ultomiris (ravulizumab-cwvz), or Piasky (crovalimab-akkz) AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent 

Length of Approval: 6 months for PNH and C3G, 9 months for IgAN, 12 months for all other indications

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. ONE of the following:
   1. The patient has a diagnosis of primary immunoglobulin A nephropathy (IgAN) AND has had improvements or stabilization with the requested agent as indicated by ONE of the following: 
      1. Decrease from baseline (prior to treatment with the requested agent) of urine protein-to-creatinine (UPCR) ratio OR
      2. Decrease from baseline (prior to treatment with the requested agent) in proteinuria OR
   2. The patient has a diagnosis Paroxysmal Nocturnal Hemoglobinuria (PNH) AND has had improvements or stabilization with the requested agent (e.g., decreased requirement of RBC transfusions, stabilization/improvement of hemoglobin, reduction of lactate dehydrogenase (LDH), stabilization/improvement of symptoms) (medical records required) OR
   3. The patient has a diagnosis of complement 3 glomerulopathy (C3G) AND BOTH of the following:
      1. The patient has had improvements or stabilization with the requested agent as indicated by ONE of the following: 
         1. Decrease from baseline (prior to treatment with the requested agent) of urine protein-to-creatinine (UPCR) ratio OR
         2. Decrease from baseline (prior to treatment with the requested agent) in proteinuria AND
      2. ONE of the following:
         1. BOTH of the following:
            1. The patient is currently treated with a maximally tolerated angiotensin-converting-enzyme inhibitor (ACEi, e.g., benazepril, lisinopril) or angiotensin II blocker (ARB, e.g., losartan), or a combination medication containing an ACEi or ARB within the past 90 days AND
            2. The patient will continue maximally tolerated ACEi, or ARB, or a combination medication containing an ACEi or ARB therapy in combination with the requested agent OR
         2. The patient has an intolerance, hypersensitivity, or FDA labeled contraindication to ALL ACEi, ARB, and combination medications containing an ACEi or ARB OR
   4. The patient has a diagnosis other than IgAN, PNH, or C3G AND has had clinical benefit with the requested agent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., hematologist, nephrologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient will NOT be using the requested agent in combination with Empaveli (pegcetacoplan), Soliris (eculizumab), Bkemv (eculizumab-aeeb), Epysqli (eculizumab-aagh), Ultomiris (ravulizumab-cwvz), or Piasky (crovalimab-akkz) AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent 

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met: 

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit​​

Length of Approval: up to 12 months