FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Aqvesme™ (mitapivat) Tablet |
Treatment of anemia in adults with alpha- or beta-thalassemia |
|
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 |
||
|
|
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. The patient has ONE of the following: A. A diagnosis of anemia with alpha-thalassemia with genetic testing confirming alpha-thalassemia OR B. A diagnosis of anemia with beta-thalassemia and ONE of the following: 1. Hemoglobin analysis showing beta-thalassemia OR 2. Genetic testing confirming beta-thalassemia AND 2. The patient has ONE of the following: A. Transfusion-dependent thalassemia (6 or more red blood cell [RBC] units transfused per 24 weeks) OR B. BOTH of the following: 1. Non-transfusion-dependent thalassemia (no more than 5 RBC units per 24 weeks) AND 2. Hemoglobin less than or equal to 10 g/dL AND 3. Iron deficiency anemia has been ruled out AND 4. 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 2. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., hematologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 3. The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please see 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. The patient 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), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 4. The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please see Quantity Limit Criteria. |
PRIOR AUTHORIZATION CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
|
Module |
Ops Set Up |
Validation Options |
Other Explanation |
|
|
Validation: Apply Baseline and go to Validation Options |
Age Verification;Continuation of Therapy |
|
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: A. 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 B. 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 |
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 |
|
|
Thalassemia |
The thalassemia syndromes are a group of inherited autosomal recessive hemoglobinopathies that result from significantly reduced or absent synthesis of normal hemoglobin. The type of thalassemia is based on the defective globin gene involved; patients with affected beta-globin genes have beta-thalassemia, and those with affected alpha-globin genes have alpha-thalassemia. Patients with thalassemia have widely variable clinical presentations, ranging from nearly asymptomatic to severe anemia requiring lifelong blood transfusions with complications in multiple organ systems.(2,5) Based on their clinical severity and transfusion requirement, thalassemia syndromes can be classified phenotypically into transfusion-dependent thalassemias (TDTs) and non-transfusion-dependent thalassemias (NTDTs).(3) Although rare in the United States, an estimated 5% of the world's population carry at least one variant globin allele.(2) The clinical course of thalassemias is highly variable depending on the mixture of inherited alleles.(4) Since almost all thalassemic conditions present with hypochromic microcytic anemia, a diagnosis of thalassemia should be considered in all individuals displaying such abnormal red blood cell features. However, it is crucial first to exclude iron deficiency anemia, which remains common in many parts of the world.(3) Hemoglobin electrophoresis may reveal common characteristics of different thalassemia subtypes, but genetic testing is required to confirm the diagnosis.(5) In general, DNA-based testing is essential for a definitive diagnosis of alpha-thalassemia. Though not required for diagnosis of beta-thalassemia, DNA-based testing should be used for confirmatory testing in patients with suspected beta-thalassemia.(2,3) Treatment of thalassemia includes transfusions, iron chelation therapy to correct iron overload (from hemolytic anemia, intestinal iron absorption, and repeated transfusions), hydroxyurea, hematopoietic stem cell transplantation, and luspatercept. Thalassemia complications arise from bone marrow expansion, extramedullary hematopoiesis, and iron deposition in peripheral tissues. These complications include morbidities affecting the skeletal system, endocrine organs, heart, and liver. Life expectancy of those with thalassemia has improved dramatically over the past 50 years with increased availability of blood transfusions and iron chelation therapy, and improved iron overload monitoring. Genetic counseling and screening in high-risk populations can assist in reducing the prevalence of thalassemia.(5) In patients with thalassemia, pyruvate kinase activity and ATP are reduced due to the overwhelmed cellular antioxidant system from the excessive oxidative stress. Aqvesme is a pyruvate kinase activator that is shown to increase hemoglobin and reduce hemolysis.(6) Aqvesme is recommended in adult patients with alpha- or beta-thalassemia. Aqvesme is intended for long-term use. It should be discontinued if no benefit in hemolytic anemia has been observed.(1) |
Efficacy |
Transfusion-Dependent Alpha- or Beta-Thalassemia: The efficacy of Aqvesme was evaluated in ENERGIZE-T, a multinational, randomized, double-blind, placebo-controlled clinical study (NCT04770779) of 258 adult patients with transfusion-dependent alpha- or beta-thalassemia, defined as having had 6 to 20 RBC units transfused and no longer than a 6-week transfusion-free period during the 24 weeks prior to randomization. Patients were included if they had a documented diagnosis of thalassemia (beta-thalassemia with or without alpha-globin gene mutations, HbE/beta-thalassemia, or alpha-Thalassemia/HbH disease).(1) Among the 258 patients with transfusion-dependent alpha- or beta-thalassemia, 171 patients were randomized to receive 100 mg of Aqvesme twice daily during the 48- week double-blind period. The median duration of treatment with Aqvesme was 48.1 weeks (range: 0.3 to 59.9 weeks). Overall, 104 (60.5%) patients were exposed to Aqvesme for greater than 48 weeks.(1) Efficacy was based upon transfusion reduction response(TRR), defined as greater than or equal to 50% reduction in the number of red blood cell units transfused with a reduction of at least 2 units of RBCs transfused in any consecutive 12-week period through Week 48 compared with baseline.(1) The results showed 30.4% of patients in the Aqvesme arm achieved TRR compared to 12.6% of patients in the placebo arm for an adjusted difference of 17.6% (P=0.0003).(1) Non-Transfusion-Dependent Alpha- or Beta- Thalassemia: The efficacy of Aqvesme was evaluated in ENERGIZE, a multinational, randomized, double-blind, placebo-controlled clinical study (NCT04770753) of 194 adults with non-transfusion-dependent alpha- or beta-thalassemia, defined as having had no more than 5 RBC units transfused during the 24‑week period prior to randomization and no RBC transfusions within 8 weeks prior to informed consent and during the screening period. Patients were included if they had a documented diagnosis of thalassemia (beta-thalassemia with or without alpha-globin gene mutations, HbE/beta-thalassemia, or alpha-thalassemia/HbH disease) and a baseline Hb concentration less than or equal to 10 g/dL. Randomization was stratified by baseline Hb concentrations (less than or equal to 9 g/dL vs 9.1-10 g/dL) and thalassemia genotype (alpha-thalassemia/HbH disease vs beta-thalassemia).(1) Among the 194 patients with non-transfusion-dependent alpha- or beta-thalassemia, 130 patients were randomized to receive 100 mg of Aqvesme twice daily during the 24-week double-blind period. The median duration of treatment with Aqvesme was 24.1 weeks (range: 1.1 to 28.1 weeks). Overall, 97 (75%) patients were exposed to Aqvesme for greater than 24 weeks.(1) Efficacy was based upon Hb response, defined as a greater than or equal to 1 g/dL increase in average Hb concentration from Week 12 through Week 24 compared with baseline and a mean change from baseline in fatigue-related symptoms and impacts assessed by a patient-reported outcome instrument, the Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-Fatigue).(1) Eighty-seven percent of patients in the Aqvesme arm experienced an increase from baseline in average Hb from Weeks 12 through 24. Of the 55 patients with Hb response in the Aqvesme arm, the average increase in Hb was 1.6 g/dL and the median duration of response was 19.6 weeks (range: 4.0 to 23.4+ weeks) during the 24-week double-blind period.(1) |
Safety |
Aqvesme has a boxed warning for hepatocellular injury: · Aqvesme can cause serious hepatocellular injury. Measure liver laboratory tests (ALT, AST, alkaline phosphatase, and total bilirubin with fractionation) at baseline and every 4 weeks for 24 weeks and then as clinically indicated. Avoid use of Aqvesme in patients with cirrhosis. Discontinue Aqvesme if hepatocellular injury is suspected.(1) Aqvesme has no FDA labeled contraindications for use.(1) Aqvesme is available only through a restricted program called the Aqvesme REMS.(1) |
Number |
Reference |
1 |
Aqvesme prescribing information. Agios Pharmaceuticals, Inc. December 2025. |
2 |
Martin A, Thompson AA. Thalassemias. Pediatr Clin North Am. 2013;60(6):1383-1391. doi:10.1016/j.pcl.2013.08.008. |
3 |
Taher AT, Farmakis D, Porter JB, Cappellini MD, Musallam KM, editors. Guidelines for the Management of Transfusion‑Dependent β‑Thalassaemia [5th ed]. Nicosia, Cyprus: Thalassaemia International Federation; 2025. https://www.medils.com/static/guide/GuidelinesForTheManagementOf_BetaTDT_May2025.pdf |
4 |
Weatherall DJ. The definition and epidemiology of non‑transfusion‑dependent thalassemia. Blood Rev. 2012;26(Suppl 1):S3–S6. doi:10.1016/S0268‑960X(12)70003‑6. |
5 |
Baird DC, Batten SH, Sparks SK. Alpha- and Beta-thalassemia: Rapid Evidence Review. Am Fam Physician. 2022;105(3):272-280. |
6 |
Kuo KHM. Pyruvate kinase activators: targeting red cell metabolism in thalassemia. Hematology Am Soc Hematol Educ Program. 2023;2023(1):114‑120. doi:10.1182/hematology.2023000468. |
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 |
|
|||||||||
|
85870050700360 |
Aqvesme |
mitapivat sulfate tab |
100 MG |
M ; N ; O ; Y |
|
|
|
|
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 |
|
|||||||||||
85870050700360 |
Aqvesme |
mitapivat sulfate tab |
100 MG |
60 |
Tablets |
30 |
Days |
|
|
|
|
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Client Formulary |
|
|||
Aqvesme |
mitapivat sulfate tab |
100 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
|
|||
Aqvesme |
mitapivat sulfate tab |
100 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
