FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
QFITLIA™ (fitusiran) Subcuteneous injection |
For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients aged 12 years and older with hemophilia A or B with or without factor VIII or IX inhibitors |
|
1 |
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
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|
Initial Evaluation Target Agent(s) will be approved when ALL of the following are met: 1. ONE of the following: A. The requested agent is eligible for continuation of therapy AND ONE of the following:
1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR 2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR B. ALL of the following: 1. ONE of the following: A. The patient has a diagnosis of Hemophilia A (factor VIII deficiency) AND ALL of the following: 1. The patient has diagnosis of congenital factor VIII deficiency confirmed by blood coagulation testing AND 2. The requested agent will be used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes AND 3. The requested agent will be used for ONE of the following: A. Primary prophylaxis in patients with severe factor VIII deficiency (factor VIII level of less than 1%) OR B. Secondary prophylaxis in patients with at least TWO episodes of spontaneous bleeding into joints AND 4. ONE of the following: A. The patient has factor VIII inhibitors AND BOTH of the following: 1. Previous prophylaxis therapy AND 2. ONE of the following: A. The patient has tried and had an inadequate response to Immune Tolerance Induction (ITI) OR B. The patient has an inhibitor level greater than or equal to 200 BU (medical records required) OR C. There is support for why the patient is NOT a candidate for ITI OR B. The patient does NOT have factor VIII inhibitors AND ONE of the following: 1. The patient has ONE of the following: A. Has tried and had an inadequate response to TWO prerequisite agents (i.e. Hemlibra AND an antihemophilic factor VIII agent) OR B. Has tried and had an inadequate response to ONE prerequisite agent AND an intolerance or hypersensitivity to ONE prerequisite agent (i.e. Hemlibra AND an antihemophilic factor VIII agent) OR C. Has an intolerance or hypersensitivity to TWO prerequisite agents (i.e. Hemlibra AND an antihemophilic factor VIII agent) OR 2. Has an FDA labeled contraindication to BOTH Hemlibra AND ALL antihemophilic Factor VIII agents OR B. The patient has a diagnosis of Hemophilia B (factor IX deficiency) AND ALL of the following: 1. The patient has diagnosis of congenital factor IX deficiency confirmed by blood coagulation testing AND 2. The requested agent will be used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes AND 3. The requested agent will be used for ONE of the following: A. Primary prophylaxis in patients with severe factor IX deficiency (factor IX level ≤ 2%) OR B. Secondary prophylaxis in patients with at least TWO episodes of spontaneous bleeding into joints AND 4. ONE of the following: A. The patient has factor IX inhibitors AND BOTH of the following: 1. Previous prophylaxis therapy AND 2. ONE of the following: A. The patient has tried and had an inadequate response to Immune Tolerance Induction (ITI) OR B. The patient has an inhibitor level greater than or equal to 200 BU (medical records required) OR C. There is support for why the patient is NOT a candidate for ITI OR B. The patient does NOT have factor IX inhibitors AND ONE of the following: 1. The patient has tried and had an inadequate response to an antihemophilic Factor IX agent OR 2. The patient has an intolerance or hypersensitivity to an antihemophilic Factor IX agent OR 3. The patient has an FDA labeled contraindication to ALL antihemophilic Factor IX agents AND 2. If the patient has an FDA labeled indication, then ONE of the following: A. The patient’s age is within FDA labeling for the requested indication for the requested agent OR B. There is support for using the requested agent for the patient’s age for the requested indication AND 3. The patient does NOT have a co-existing thrombophilic disorder or a history of, or risk factors predisposing to, thrombosis AND 4. The requested agent will NOT be used for the treatment of breakthrough bleeding AND 2. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., prescriber working in a hemophilia treatment center, hematologist with hemophilia experience), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 3. The requested agent will NOT be used in combination with immune tolerance induction with clotting factor products (i.e., factor VIII or factor IX concentrates) as prophylactic therapy, hemophilia bypassing agent prophylaxis (i.e., factor VIIa or anti-inhibitor coagulant complex), or emicizumab for hemophilia A with inhibitors (Note: Factor VIII or factor IX products can be administered for the treatment of breakthrough bleeds when occurring more than 7 days after initiation of QFITLIA) AND 4. The patient has an antithrombin (AT) activity level of ≥ 60% at baseline (e.g., prior to therapy with the requested agent) and AT-activity will be monitored regularly as outlined in the FDA labeling AND 5. The patient does NOT have hepatic impairment (Child-Pugh Class A, B, and C) Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. 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: A. The patient has had improvement or stabilization with the requested agent as indicated by the number of breakthrough bleeding episodes (medical records required) OR B. There is support for the continued use of the requested agent (medical records required) AND 3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., prescriber working in a hemophilia treatment center, hematologist with hemophilia experience), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 4. The requested agent will NOT be used in combination with immune tolerance induction with clotting factor products (i.e., factor VIII or factor IX concentrates) as prophylactic therapy, hemophilia bypassing agent prophylaxis (i.e., factor VIIa or anti-inhibitor coagulant complex), or Emicizumab for hemophilia A with inhibitors (Note: Factor VIII or factor IX products can be administered for the treatment of breakthrough bleeds when occurring more than 7 days after initiation of QFITLIA) Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
PRIOR AUTHORIZATION CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
Module |
Ops Set Up |
Validation Options |
Other Explanation |
|
Documentation: Requirements as noted within the policy;Validation: Apply Baseline and go to Validation Options |
Age Verification;Continuation of Therapy;Contraind. - intolerance - or hypersensitivity to prereq.;Other (see Other explanation field) |
*Review info: Support for why the patient is NOT a candidate for ITI |
QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
Universal QL |
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 OR 3. BOTH of the following: 1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND 2. There is support for therapy with a higher dose for the requested indication Length of Approval: up to 12 months |
QUANTITY LIMIT CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
Module |
Ops Set Up |
Validation Options |
Other Explanation |
Universal QL |
Validation: Apply Baseline and go to Validation Options |
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Hemophilia A and Hemophilia B |
Hemophilia A, also called Factor VIII (FVIII) deficiency or classic hemophilia, is a genetic disorder caused by missing or defective Factor VIII (FVIII), a clotting protein. Although it is passed down from mothers to children, about 1/3 of cases found have no previous family history.(2) Treatment for hemophilia A is dependent on several factors and there is not a universal therapy that will work for all patients. Clinically, the hallmark of bleeding in hemophilia is bleeding into the joints, muscles, and soft tissues. The severity and the risk of that bleeding can be correlated to the residual factor activity that can be measured in the blood. Patients with severe disease have less than 1% residual activity and often have zero. These are the patients who are at risk for spontaneous and traumatic bleeding. Having over 5% residual amount makes bleeding into the joints very unusual (although not inconceivable), and most bleeding is triggered only by trauma. Residual activity of 1-5% appears for the most part to prevent spontaneous bleeding, but patients can still be at risk for joint bleeds with even relatively minor trauma.(3) The main goal of any therapy is to completely prevent bleeding. The current World Hemophilia Federation Guidelines for the Management of Hemophilia state:(5)
Approximately 1 in 5 people with hemophilia A will develop an antibody, called an inhibitor, to the clotting factor concentrate(s) used to treat or prevent their bleeding episodes. Developing an inhibitor is one of the most serious and costly medical complications of a bleeding disorder because it becomes more difficult to treat bleeds. Inhibitors most often appear in the first 50 exposure days of clotting factor concentrates.(3,6) The National Hemophilia Foundation classifies inhibitors as low responding and high responding in addition to low titer (less than 5 BU) and high titer (greater than or equal to 5 BU). In low responding inhibitors, when the patient receives Factor VIII the inhibitor titer does not rise. These patients can be treated with higher doses of the CFC. If the inhibitor titer increases with CFC it is considered high responding. For high responding inhibitors, the situation becomes much more complicated as even large doses of infused CFC are often rendered ineffectual by the sheer potency of the antibody response.(4) Hemophilia B, or Christmas disease, is an inherited, recessive disorder that involves deficiency of functional coagulation factor IX (FIX) in plasma. Hemophilia B is caused by a variety of defects in the F9 gene. As this gene is carried on the X chromosome, the disease usually manifests in males and is transmitted by females who carry the causative mutation on one of their X chromosomes. Spontaneous mutation and acquired immunologic processes can result in this disorder, as well. Hemophilia B constitutes about 20% of hemophilia cases. Hemophilia B may be classified as severe, moderate, or mild, based on the plasma levels of FIX (< 1%, 1-5%, 6-40%, respectively). About 50% of persons with hemophilia B have FIX levels greater than 1%.(6) Approximately 3-5% of patients with severe hemophilia B develop alloantibody inhibitors that can neutralize FIX. These inhibitors are usually immunoglobulin G antibodies and appear after the first infusions of FIX concentrate. Both genetic and environmental factors determine the frequency of inhibitor development. Inhibitors most often appear during the first 50 times a person is treated with clotting factor concentrates, but they can appear at any time.(6,7) Factor IX is the treatment of choice for acute hemorrhage or presumed acute hemorrhage. Recombinant factor IX is the preferred source for replacement therapy. While plasma-derived FIX products are still available, approximately 75% of the hemophilia community takes a recombinant FIX product. The Medical and Scientific Advisory Council (MASAC) of the National Bleeding Disorders Foundation encourages the use of recombinant clotting factor products because they are safer. Patients with severe hemophilia may be on a routine treatment regimen, called prophylaxis, to maintain enough clotting factor in their bloodstream to prevent bleeds. MASAC recommends prophylaxis as optimal therapy for children with severe hemophilia B. Aminocaproic acid is an antifibrinolytic, preventing the breakdown of blood clots. It is often recommended before dental procedures, and to treat nose and mouth bleeds.(6) Inhibitor development is the most severe complication of treatment for patients with inherited hemophilia A or B. Choice of product for treatment depends on multiple factors, including type of inhibitor (low- or high- responding), current titer of inhibitor, location of the bleed, previous response to a product, availability of clinical trial data supporting use of the products and concomitant medications (e.g., emicizumab). For high-titer inhibitors, immune tolerance induction (ITI) is the best option for inhibitor eradication.(8) If left unchecked a persistent inhibitor will present a severe burden on patients and families as the ongoing physical, emotional, and in many cases financial toll continue to intensify. Healthcare providers will often attempt to proactively stamp out an inhibitor through ITI. ITI is an approach to inhibitor eradication where the body’s immune system begins to tolerate a therapy after daily doses of factor are administered over time. The majority of people who undergo ITI therapy will see an improvement within 12 months, but more difficult cases can take two years or longer. There is a general consensus that failure of ITI is the inability to achieve successful tolerance within 2-3 years of initiation of an ITI regimen.(5) The Hemophilia Federation of America recommends that if success has not occurred within 33 months of beginning ITI and there is a lack of a 20% decrease in the inhibitor titer over a 6 month period that it is considered a failure.(9) In the cases of high-responding inhibitors, treatment is based on several components including the type of hemophilia and the nature of the bleed. During a life or limb-threatening bleeding episode physicians can remove antibodies from the body using plasmapheresis. This is only a temporary solution, however, as within a few days the body will produce large amounts of new antibodies. For the person with high responding inhibitors there are therapies that can effectively treat bleeds by circumventing the need to replace FVIII. These agents are commonly referred to as bypassing agents (BPAs) and include activated prothrombin complex concentrate (aPCC) and recombinant activated Factor VII concentrates (rFVIIa).(10) |
Efficacy |
QFITLIA is a double-stranded siRNA that causes degradation of AT messenger RNA (mRNA) through RNA interference, reducing plasma AT levels.(1) The efficacy and safety of QFITLIA in adult and pediatric patients aged 12 years and older with hemophilia A or B with or without inhibitors were established in two clinical studies:(1)
Patients in the above parent studies rolled over into the long-term extension study ATLAS-OLE (NCT03754790). The clinical studies ATLAS-INH and ATLAS-A/B tested an 80 mg monthly fixed dose of QFITLIA. Because of thrombotic events with this dose, the QFITLIA AT-DR targeting AT activity of 15–35% was implemented in ATLAS-OLE. The AT-DR was initiated when studies ATLAS-INH and ATLAS-A/B were nearly completed, therefore, the efficacy of QFITLIA AT-DR treatment was assessed by comparing the QFITLIA AT-DR treatment data from the long-term extension study ATLAS-OLE to the control data from studies ATLAS-INH and ATLAS-A/B. The efficacy analyses were conducted according to the intent to treat (ITT) principle preserving the randomization in the parent studies.(1) ATLAS-OLE: A total of 227 patients rolled over from two clinical studies (ATLAS-INH and ATLAS-A/B) and ATLAS-PPX, a crossover study in patients previously on CFC or BPA prophylaxis, and were treated with QFITLIA in ATLAS-OLE. This multicenter open-label extension study evaluated the long-term safety and efficacy of QFITLIA in adult and pediatric males aged ≥12 years with hemophilia A or B, with or without inhibitory antibodies to FVIII or FIX. Eligible patients initially received QFITLIA 80 mg subcutaneously once monthly. The study was amended to evaluate the efficacy and safety of the antithrombin-based dose regimen (AT-DR). A total of 213 patients were subsequently transitioned to AT-DR targeting AT activity of 15–35%.(1) In the AT-DR, the QFITLIA starting dose was 50 mg every two months, and dosing was individually adjusted based on AT activity level using the INNOVANCE Antithrombin assay. The dose could be increased to 50 mg or 80 mg every month or decreased to 20 mg every two months or 20 mg every month. QFITLIA was discontinued if AT activity was <15% at the lowest dose. No patients required escalation to 80 mg every month to achieve the target AT range. The dose required to maintain AT activity 15–35% in patients who initiated dosing on 50 mg every two months was: 50 mg every two months (35.8% of patients), 50 mg every month (15.7% of patients), 20 mg every two months (30.9% of patients), or 20 mg every month (2.9% of patients). A total of 14.7% of patients discontinued QFITLIA due to more than one AT activity <15%.(1) Patients with known co-existing coagulation disorders other than hemophilia A or B, increased risk of thrombosis as assessed by history of arterial or venous thromboembolism, significant valvular disease or atrial fibrillation, or co-existing thrombophilic disorder (e.g., Factor V Leiden mutation), AT activity <60% at screening, platelet count ≤100,000/μL, eGFR ≤45 mL/min (using the MDRD), or clinically significant hepatic disease (Child-Pugh Class A, B, and C) were not eligible for enrollment.(1) The efficacy of QFITLIA AT-DR in ATLAS-OLE was evaluated for a duration of 7 months (primary efficacy period) following a 6-month dose adjustment period. The median observed annualized bleeding rate (IQR) for treated bleeds was 3.7 (0.0; 7.5) overall, 1.9 (0.0; 5.6) in inhibitor patients and 3.8 (0.0; 11.2) in non-inhibitor patients.(1) |
Safety |
QFITLIA has boxed warnings for Thrombotic Events and Acute and Recurrent Gallbladder Disease: Serious thrombotic events have occurred in QFITLIA-treated patients with risk factors for thromboembolism including persistent antithrombin (AT) activity less than 15%, use of QFITLIA 80 mg once monthly, presence of indwelling venous catheters, and in the post-operative setting when bleed management guidelines were not followed. Monitor AT activity using an FDA-cleared test and target AT activity 15– 35% to reduce the risk of thrombosis. Monitor patients for signs and symptoms of thrombotic events. Interrupt QFITLIA in patients with a thrombotic event and manage as clinically indicated. Acute and recurrent gallbladder disease, including cholelithiasis and cholecystitis have occurred in QFITLIA-treated patients, some of whom required cholecystectomy or had complications (e.g., pancreatitis) related to gallbladder disease. Monitor patients for signs and symptoms of acute and recurrent gallbladder disease. Consider interruption or discontinuation of QFITLIA if gallbladder disease occurs. Consider alternative treatment for hemophilia in patients with a history of symptomatic gallbladder disease. |
Number |
Reference |
1 |
QFITLIA prescribing information. Genzyme Corporation. March 2025. |
2 |
Hemophilia A | NBDF. National Bleeding Disorders Foundation. https://www.bleeding.org/bleeding-disorders-a-z/types/hemophilia-a. |
3 |
One size does not fit all: Individualized therapy | NBDF. National Bleeding Disorders Foundation. Published February 8, 2017. https://www.hemophilia.org/educational-programs/education/online-education/one-size-does-not-fit-all-individualized-therapy. |
4 |
Kovalich D, Goto S, National Hemophilia Foundation, et al. Living With an Inhibitor: Your Guide to Managing Hemophilia With Inhibitors.; 2023. https://www.bleeding.org/sites/default/files/document/files/living-with-inhibitors.pdf. |
5 |
Srivastave A, Santagostino E, Dougall A, et al. World Federation of Hemophilia Guidelines for the Management of Hemophilia. 3rd edition. August 2020. |
6 |
Hemophilia B | NBDF. National Bleeding Disorders Foundation. https://www.bleeding.org/bleeding-disorders-a-z/types/hemophilia-b. |
7 |
Testing for inhibitors and hemophilia. Hemophilia. Published May 15, 2024. https://www.cdc.gov/hemophilia/testing/testing-for-inhibitors-and-hemophilia.html?CDC_AAref_Val=https://www.cdc.gov/ncbddd/hemophilia/inhibitors.html. |
8 |
Medical and Scientific Advisory Council (MASAC) MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders. Document #280. August 2023. |
9 |
Dimichele DM, Hoots WK, Pipe SW, et al. International workshop on immune tolerance induction: consensus recommendations. Haemophilia (2007), 13 (Suppl. 1), 1-22. |
10 |
National Hemophilia Foundation Bleeding Disorders A-Z Overview Inhibitors Treatment for Inhibitors. Treatment for Inhibitors | National Hemophilia Foundation. |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Final Module |
Target Agent GPI |
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Targeted NDCs When Exclusions Exist |
Final Age Limit |
Preferred Status |
Effective Date |
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85100725202020 |
Qfitlia |
fitusiran sodium subcutaneous soln |
20 MG/0.2ML |
M ; N ; O ; Y |
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|
8510072520D520 |
Qfitlia |
fitusiran sodium subcutaneous soln auto-inj |
50 MG/0.5ML |
M ; N ; O ; Y |
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POLICY AGENT SUMMARY QUANTITY LIMIT
Target Agent GPI |
Target Brand Name(s) |
Target Generic Name(s) |
Strength |
QL Amount |
Dose Form |
Days Supply |
Duration |
Targeted NDCs When Exclusions Exist |
Age Limit |
Effective Date |
Term Date |
|
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85100725202020 |
Qfitlia |
fitusiran sodium subcutaneous soln |
20 MG/0.2ML |
1 |
Vial |
28 |
|
|
|
|
|
8510072520D520 |
Qfitlia |
fitusiran sodium subcutaneous soln auto-inj |
50 MG/0.5ML |
1 |
Pen |
28 |
|
|
|
|
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CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Client Formulary |
|
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Qfitlia |
fitusiran sodium subcutaneous soln |
20 MG/0.2ML |
Commercial ; HIM ; WY NetR-Commercial Custom |
Qfitlia |
fitusiran sodium subcutaneous soln auto-inj |
50 MG/0.5ML |
Commercial ; HIM ; WY NetR-Commercial Custom |
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
|
|||
Qfitlia |
fitusiran sodium subcutaneous soln |
20 MG/0.2ML |
Commercial ; HIM ; WY NetR-Commercial Custom |
Qfitlia |
fitusiran sodium subcutaneous soln auto-inj |
50 MG/0.5ML |
Commercial ; HIM ; WY NetR-Commercial Custom |
