Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual
Policy #:	2022046
Category:	Pharmacy
Initiated:	October 2022
Last Review:	November 2025

Betibeglogene autotemcel (e.g., Zynteglo)

Description:

Betibeglogene autotemcel is a cell-based gene therapy for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions. Beta-thalassemia is an inherited blood disease caused by mutations in the beta-globin gene and characterized by significantly reduced or absent adult hemoglobin production. Betibeglogene autotemcel treats individuals with beta-thalassemia in its most severe form – transfusion-dependent beta-thalassemia. Betibeglogene autotemcel is developed by adding functional copies of a modified form of the beta-globin gene to the patient’s own hematopoietic stem cells in the ex vivo setting. This is then administered as a single IV infusion in the hospital inpatient setting.

Regulatory Status

Betibeglogene autotemcel (e.g., Zynteglo) was approved by the U.S. Food and Drug Administration (FDA) on August 17th, 2022, for the treatment of adult and pediatric individuals with beta-thalassemia who require regular RBC transfusions.

Coding

See CPT/HCPC Code section below.

Policy/
Coverage:

Prior Approval is required for betibeglogene autotemcel (e.g., Zynteglo).

The use of this drug/therapy requires documentation of direct involvement and ordering by a physician with expertise in specified condition and in a center approved for administration of CAR-T or gene product.

Effective January 21, 2026

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Betibeglogene autotemcel (e.g., Zynteglo), meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered, when ALL the following criteria are met:

1. Adult or pediatric individual has documented diagnosis of Beta-thalassemia as evidenced by one of the following genotypes confirmed by globin gene testing (Zynteglo, 2022; Locatelli, 2022):

a. Beta0/Beta0; OR

b. Beta0/Beta0 – like (see policy guidelines); OR

c. Non-Beta0/Beta0 (see policy guidelines); AND

2. Individual requires regular peripheral blood transfusions to maintain target hemoglobin levels as defined by documentation of the following:

a. History of receiving transfusions of greater than or equal to 100 ml per kilogram of body weight of packed red blood cells per year; OR

b. History of receiving greater than or equal to 8 transfusions per year in the prior 2 years at the time of treatment decision (Locatelli, 2022); AND

3. Applicable only to individuals less than 18 years of age: Individual does not have an available and willing human leukocyte antigen-identical or human leukocyte antigen-matched donor. (Locatelli, 2022) (Kassim 2024); AND

4. Individual has not received allogenic hematopoietic stem cell transplant (Locatelli, 2022); AND

5. Individual meets the institutional requirements for a stem cell transplant procedure where the individual is expected to receive gene therapy (see policy guidelines):

a. Adequate Karnofsky performance status or Lansky performance status

b. Absence of advanced liver disease

c. Adequate estimated glomerular filtration rate (eGFR)

d. Adequate diffusing capacity of the lungs for carbon monoxide (DLCO)

e. Adequate heart function

f. Absence of clinically significant active infection(s)

6. Individual does not have a history of receiving gene therapy or is not under consideration for treatment with another gene therapy for beta thalassemia.

Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria

Betibeglogene autotemcel (e.g., Zynteglo), for any indication or circumstance not described above, does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes.

Repeat treatment with betibeglogene autotemcel is considered investigational.

For members with contracts without Primary Coverage Criteria, Betibeglogene autotemcel (e.g., Zynteglo), for the treatment of any indication or any circumstance not described above is considered not Medically Necessary or is investigational. Investigational services are Plan exclusions.

POLICY GUIDELINES

Examples of beta thalassemia genotypes

1. Beta0/Beta0 – like:

a. Beta0/Beta + (IVS-I-110)

b. Beta + (IVS-I-110)/Beta+ (IVS-I-110)

2. Non-Beta0/Beta0:

a. Beta0/Beta+

b. BetaE/Beta0

c. Beta+/Beta+

Institutional requirements for a stem cell transplant procedure where the individual is expected to receive gene therapy may include:

1. Adequate cell counts defined as WBC greater than or equal to 3 × 1 billion/L, ANC greater than or equal to 1 x 1 billion/L (greater than or equal to 0.5 x1 billion/L for those on hydroxyurea treatment) or platelets greater than or equal to 50 to 100 × 1 billion/L.

2. Adequate heart function defined as cardiac T2* greater than or equal to 10 ms.

3. Absence of advanced liver disease (defined as ALT greater than 3x ULN, AST greater than 3x ULN, direct bilirubin value greater than 2x ULN, PT INR greater than 1.5x ULN, history of cirrhosis or any evidence of bridging fibrosis, or active hepatitis on liver biopsy).

4. Adequate lung function defined as DLCO greater than or equal to 50% of predicted value and baseline oxygen saturation greater than or equal to 90% without supplemental oxygen.

5. Adequate performance status defined as Karnofsky performance status greater than 60 (greater than or equal to 16 years of age) or Lansky performance status greater than 60 (less than 16 years of age).

6. Adequate kidney function defined as eGFR greater than or equal to 60 to 70 mL/min/1.73 square meters of body surface area.

DOSAGE AND ADMINISTRATION

For FDA labeled indications, Betibeglogene autotemcel (e.g., Zynteglo) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified below.

The minimum recommended dose of betibeglogene autotemcel is 5.0 million CD34+ cells/kg of body weight administered as an IV injection by a healthcare professional in the hospital inpatient setting.

Dosing limits: one injection per lifetime.

Other Considerations

1. Prophylaxis for hepatic veno-occlusive disease is recommended. Prophylaxis for seizures should be considered.

2. Monitor platelet counts until platelet engraftment and recovery are achieved. Individuals should be monitored for thrombocytopenia and bleeding.

3. Monitor absolute neutrophil counts after betibeglogene autotemcel infusion. If neutrophil engraftment does not occur administer rescue cells.

4. Monitor individuals at least annually for hematologic malignancies for at least 15 years after betibeglogene autotemcel infusion.

5. Individuals should not take prophylactic anti-retroviral medications or hydroxyurea for at least 1 month prior to mobilization or the expected duration for elimination of the medications, and until all cycles of apheresis are completed as anti-retroviral medications may interfere with manufacturing of the apheresed cells.

6. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. After betibeglogene autotemcel infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate:

Betibeglogene autotemcel (e.g., Zynteglo) is available as a single dose intravenous infusion containing a minimum of 5.0 X 1 million CD34+cells/kg of body weight, in one or more infusion bags.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Effective October 23, 2024 January 20, 2026

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Betibeglogene autotemcel meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:

1. Individual is at least 4 years of age (Zynteglo, 2022); AND

2. Individual has documented diagnosis of Beta-thalassemia as evidenced by one of the following genotypes confirmed by globin gene testing (Locatelli, 2022):

a. Beta0/Beta0; OR

b. Beta0/Beta0 – like (see policy guidelines); OR

c. Non-Beta0/Beta0 (see policy guidelines); AND

3. Individual requires regular peripheral blood transfusions to maintain target hemoglobin levels as defined by documentation of the following:

a. History of receiving transfusions of ≥100 ml per kilogram of body weight of packed red blood cells per year; OR

b. History of receiving > 8 transfusions per year in the prior 2 years at the time of treatment decision (Locatelli, 2022); AND

4. Applicable only to individuals less than 18 years of age: Individual does not have an available and willing matched HLA-identical sibling or haploidentical related hematopoietic cell donor (Locatelli, 2022) (Kassim 2024); AND

5. Individual has not received allogenic hematopoietic stem cell transplant (Locatelli, 2022); AND

6. Individual meets the institutional requirements for a stem cell transplant procedure where the individual is expected to receive gene therapy (see policy guidelines):

a. Adequate Karnofsky performance status or Lansky performance status

b. Absence of advanced liver disease

c. Adequate estimated glomerular filtration rate (eGFR)

d. Adequate diffusing capacity of the lungs for carbon monoxide (DLCO)

e. Adequate heart function

f. Absence of clinically significant active infection(s)

7. Individual does not have a history of receiving gene therapy or is not under consideration for treatment with another gene therapy for beta thalassemia; AND

8. Must be dosed in accordance with the FDA label.

Policy guidelines

Examples of beta thalassemia genotypes

1. Beta0/Beta0 – like:

a. Beta0/Beta + (IVS-I-110)

b. Beta + (IVS-I-110)/Beta+ (IVS-I-110)

2. Non-Beta0/Beta0:

a. Beta0/Beta+

b. BetaE/Beta0

c. Beta+/Beta+

Institutional requirements for a stem cell transplant procedure where the individual is expected to receive gene therapy may include:

1. Adequate cell counts defined as WBC > 3 × 1 billion/L, ANC > 1 x 1 billion/L (> 0.5 x1 billion/L for those on hydroxyurea treatment) or platelets > 50 to 100 × 1 billion/L

2. Adequate heart function defined as cardiac T2* > 10 ms

3. Absence of advanced liver disease (defined as ALT > 3x ULN, AST > 3x ULN, direct bilirubin value > 2x ULN, PT INR > 1.5x ULN, history of cirrhosis or any evidence of bridging fibrosis, or active hepatitis on liver biopsy)

4. Adequate lung function defined as DLCO > 50% of predicted value and baseline oxygen saturation > 90% without supplemental oxygen

5. Adequate performance status defined as Karnofsky performance status > 60 (≥ 16 years of age) or Lansky performance status > 60 (< 16 years of age)

6. Adequate kidney function defined as eGFR > 60 to 70 mL/min/1.73 square meters of body surface area.

Dosage and Administration

Dosing per FDA Guidelines

The minimum recommended dose of betibeglogene autotemcel is 5.0 million CD34+ cells/kg of body weight administered as an IV injection by a healthcare professional in the hospital inpatient setting.

Dosing limits: one injection per lifetime.

Other Considerations

1. Prophylaxis for hepatic veno-occlusive disease is recommended. Prophylaxis for seizures should be considered.

2. Monitor platelet counts until platelet engraftment and recovery are achieved. Individuals should be monitored for thrombocytopenia and bleeding.

3. Monitor absolute neutrophil counts after betibeglogene autotemcel infusion. If neutrophil engraftment does not occur administer rescue cells.

4. Monitor individuals at least annually for hematologic malignancies for at least 15 years after betibeglogene autotemcel infusion.

5. Individuals should not take prophylactic anti-retroviral medications or hydroxyurea for at least 1 month prior to mobilization or the expected duration for elimination of the medications, and until all cycles of apheresis are completed as anti-retroviral medications may interfere with manufacturing of the apheresed cells.

6. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. After betibeglogene autotemcel infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate:

a. Betibeglogene autotemcel is available as a single dose intravenous infusion containing a minimum of 5.0 X 1 million CD34+cells/kg of body weight, in one or more infusion bags.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Betibeglogene autotemcel, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

Repeat treatment with betibeglogene autotemcel is considered investigational.

For members with contracts without primary coverage criteria, Betibeglogene autotemcel, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective October 26, 2022 to October 22, 2024

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

1. Individual has documented diagnosis of Beta-thalassemia by globin gene testing (Locatelli, 2022); AND

2. Individual requires regular peripheral blood transfusions to maintain target hemoglobin levels (Locatelli, 2022); AND

3. Individual has documented history of receiving transfusions of ≥100 ml per kilogram of body weight of packed red cells per year or who had disease that had been managed under standard thalassemia guidelines with ≥8 transfusions per year in the previous 2 years at the time of treatment decision (Locatelli, 2022); AND

4. Individual has Karnofsky performance status of ≥ 80 for adults (≥16 years of age) or a Lansky performance status of ≥ 80 for adolescents (< 16 years of age) (Locatelli, 2022); AND

5. Individual has negative serologic test for HIV infection (as per US FDA prescribing label, apheresis material from individuals with a positive test for HIV will not be accepted for betibeglogene autotemcel manufacturing) (Locatelli, 2022); AND

6. Individual does not have any of the following:

a. Availability of human leukocyte antigen-identical or human leukocyte antigen-matched donor (Locatelli, 2022); OR

b. T2*-weighted magnetic resonance imaging measurement of myocardial iron of less than 10 msec or other evidence of severe iron overload in the opinion of treating physician (Locatelli, 2022); OR

c. Advanced liver disease (meets any one of the following) (Locatelli, 2022):

i. Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value greater than 3 times the upper limit of normal; OR

ii. Baseline prothrombin time or partial thromboplastin time greater than 1.5 times the upper limit of normal; OR

iii. Magnetic resonance imaging of the liver demonstrating clear evidence of cirrhosis; OR

iv. Liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or active hepatitis; OR

d. Baseline estimated glomerular filtration rate less than 70 mL/min/1.73 square meters (FDA, 2022); OR

e. History of receiving prior gene therapy or allogenic hematopoietic stem cell transplant (Locatelli, 2022); OR

f. Any prior or current malignancy (with the exception of adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin) or myeloproliferative or significant immunodeficiency disorder (Locatelli, 2022); OR

g. Any immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome and familial adenomatous polyposis) (Locatelli, 2022); OR

h. Active, uncontrolled HCV or HBV infection (Locatelli, 2022); OR

i. Contraindication to the use of granulocyte colony stimulating factor (G-CSF), plerixafor, busulfan, or any other medicinal products required during myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients (Locatelli, 2022); OR

j. A white blood cell count less than 3 billion/L, and/or platelet count less than 100 billion/L not related to hypersplenism (Locatelli, 2022).

Dosage and Administration

Dosing per FDA Guidelines

The minimum recommended dose of betibeglogene autotemcel is 5.0 million CD34+ cells/kg of body weight administered as an IV injection by a healthcare professional in the hospital inpatient setting.

Dosing limits: one injection per lifetime.

Other Considerations

· Prophylaxis for hepatic veno-occlusive disease is recommended. Prophylaxis for seizures should be considered.

· Monitor platelet counts until platelet engraftment and recovery are achieved. Individuals should be monitored for thrombocytopenia and bleeding.

· Monitor absolute neutrophil counts after betibeglogene autotemcel infusion. If neutrophil engraftment does not occur administer rescue cells.

· Monitor individuals at least annually for hematologic malignancies for at least 15 years after betibeglogene autotemcel infusion.

· Individuals should not take prophylactic anti-retroviral medications or hydroxyurea for at least 1 month prior to mobilization or the expected duration for elimination of the medications, and until all cycles of apheresis are completed as anti-retroviral medications may interfere with manufacturing of the apheresed cells.

· Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. After betibeglogene autotemcel infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate.

Betibeglogene autotemcel is available as a single dose intravenous infusion containing a minimum of 5.0 X 10 the power of 6 CD34+cells/kg of body weight, in one or more infusion bags.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

1. Individual has availability of human leukocyte antigen-identical or human leukocyte antigen-matched donor.

2. Individual has T2*-weighted magnetic resonance imaging measurement of myocardial iron of less than 10 msec or other evidence of severe iron overload in the opinion of treating physician.

3. Individual has advanced liver disease (meets any one of the following):

a. Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value greater than 3 times the upper limit of normal.

b. Baseline prothrombin time or partial thromboplastin time greater than 1.5 times the upper limit of normal.

c. Magnetic resonance imaging of the liver demonstrating clear evidence of cirrhosis.

d. Liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or active hepatitis.

4. Individual has baseline estimated glomerular filtration rate less than 70 mL/min/1.73 square meters.

5. Individual has history of receiving prior gene therapy or allogenic hematopoietic stem cell transplant.

6. Individual has any prior or current malignancy (with the exception of adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin) or myeloproliferative or significant immunodeficiency disorder.

7. Individual has any immediate family member (i.e. parent or siblings) with a known Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer syndrome and familial adenomatous polyposis).

8. Individual has active, uncontrolled HCV or HBV infection.

9. Individual has contraindication to the use of granulocyte colony stimulating factor (G-CSF), plerixafor, busulfan, or any other medicinal products required during myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.

10. Individual has a white blood cell count less than 3 billion/L, and/or platelet count less than 100 billion/L not related to hypersplenism.

Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:

The efficacy of ZYNTEGLO was evaluated in 2 ongoing Phase 3 open-label, single-arm, 24-month, multicenter studies (Study 1 and Study 2) in 41 patients aged 4 to 34 years with Beta-thalassemia requiring regular transfusions. Following completion of the 24-month parent studies, patients were invited to enroll in an ongoing long-term safety and efficacy follow-up study for an additional 13 years.

Patients were considered to be eligible for the Phase 3 studies if they had a history of transfusions of at least 100 mL/kg/year of packed red blood cells (pRBCs) or with 8 or more transfusions of pRBCs per year in the 2 years preceding enrollment.

Study 1 (NCT02906202) is an ongoing Phase 3 open-label, single-arm, 24-month study to evaluate the efficacy of ZYNTEGLO in 23 patients with Beta-thalassemia requiring regular transfusions and with a non-Beta0/Beta0 genotype. Nineteen out of 23 patients have rolled over into a long-term follow-up study (Study 3, NCT02633943) after Month 24.

The median (min, max) duration of follow-up is 29.5 (13.0, 48.2) months. All patients remain alive at last follow-up. There were no cases of graft versus-host disease (GVHD), graft failure, or graft rejection in the clinical studies.

The benefit of ZYNTEGLO was established based on achievement of transfusion independence (TI), defined as a weighted average Hb ≥ 9 g/dL without any pRBC transfusions for a continuous period of ≥ 12 months at any time during the study, after infusion of ZYNTEGLO. Of 22 patients evaluable for TI, 20 (91%, 95% CI: 71, 99) achieved TI with a median (min, max) weighted average Hb during TI of 11.8 (9.7, 13.0) g/dL. All patients who achieved TI maintained TI, with a min, max duration of ongoing TI of 15.7+, 39.4+ months (N = 20). The median (min, max) time to last pRBC transfusion prior to TI was 0.9 (0.5, 2.4) months following ZYNTEGLO infusion. For the patients who were evaluable for TI and did not achieve TI (N = 2), a reduction of 32% and 31% in transfusion volume requirements and a reduction of 30% and 26% in transfusion frequency were observed from 6 months post-drug product infusion to last follow-up compared to pre-enrollment requirements.

Study 2 (NCT03207009) is an ongoing Phase 3 open-label, single-arm, 24-month study to evaluate the efficacy of ZYNTEGLO in 18 patients with Beta-thalassemia requiring regular transfusions and a Beta0/Beta0 or non-Beta0/Beta0 (IVS-I-110/IVS-I-110 or IVS-I-110/ Beta0) genotype. Ten out of 18 patients have rolled over into a long-term follow-up study (Study 3, NCT02633943) after Month 24.

The median (min, max) duration of follow-up is 24.6 (4.1, 35.5) months. All patients remain alive at last follow-up. There were no cases of GVHD, graft failure, or graft rejection in the clinical study.

The efficacy of ZYNTEGLO was established based on achievement of TI, defined the same as Study 1. Fourteen patients are evaluable for TI. Of these, 12/14 (86%, 95% CI: 57, 98) achieved TI with a median (min, max) weighted average Hb during TI of 10.20 (9.3, 13.7) g/dL. All patients who achieved TI maintained TI, with a min, max duration of ongoing TI of 12.5+, 32.8+ months (N = 12). The median (min, max) time to last pRBC transfusion prior to TI was 0.8 (0.0, 1.9) months following ZYNTEGLO infusion. For the patients who were evaluable for TI and did not achieve TI (N = 2), a reduction of 92% and 3% in transfusion volume requirements and a reduction of 87% and 21% in transfusion frequency were observed from 6 months post-drug product infusion to last follow-up compared to pre-enrollment requirements.

All 32 patients in the Phase 3 studies who achieved TI with ZYNTEGLO maintained TI. These patients exhibited durable normal or near-normal total hemoglobin levels with a median (min, max) unsupported total Hb of 11.4 (9.5, 14.8) g/dL at last follow-up.

2023 Update

Annual policy review completed with a literature search using the MEDLINE database through November 2023. No new literature was identified that would prompt a change in the coverage statement.

2024 Update

Annual policy review completed with a literature search using the MEDLINE database through November 2024. No new literature was identified that would prompt a change in the coverage statement.

2025 Update

Transfusion-dependent β-thalassaemia (TDT) is a severe disease, resulting in lifelong blood transfusions, iron overload, and associated complications. Betibeglogene autotemcel (beti-cel) gene therapy uses autologous haematopoietic stem and progenitor cells (HSPCs) transduced with BB305 lentiviral vector to enable transfusion independence.

HGB-212 was a non-randomised, multicentre, single-arm, open-label, phase 3 study of beti-cel in patients with TDT conducted at eight centres in France, Germany, Greece, Italy, the UK, and the USA. Patients with both beta null alleles, or the following combinations: beta null plus pathogenic IVSI-100 allele or two pathogenic IVSI-100 allele genotypes, clinically stable TDT, and a transfusion history of at least 100 mL/kg per year of packed red blood cells (pRBCs) or at least eight transfusions of pRBCs per year in the 2 years before enrolment were eligible for participation. After undergoing HSPC mobilisation and busulfan-based, pharmacokinetic-adjusted myeloablative conditioning, patients were infused with beti-cel and followed up for 24 months. The primary efficacy outcome was transfusion independence, defined as weighted average haemoglobin level of 9 g/dL or above without pRBC transfusions for 12 or more months. The primary outcome was measured in all patients who received an infusion of beti-cel (transplant population); safety was evaluated in all patients who initiated study treatment (intention-to-treat population). Patients were eligible to enroll in the ongoing 13-year long-term follow-up study (for a total of 15 years), LTF-303 (registered at ClinicalTrials.gov, NCT02633943). This trial, HGB-212, was registered at ClinicalTrials.gov (NCT03207009), and is complete.

From June 8, 2017, to March 12, 2020, 20 patients were screened for eligibility. One patient was ineligible, and one withdrew consent before HSPC mobilisation and myeloablative conditioning. Of the 18 patients who received beti-cel, ten (56%) were male and eight (44%) were female; 13 (72%) were younger than 18 years at the time of informed consent, and five (28%) were older than 18 years. 12 (67%) patients had β0/β0 genotypes, three (17%) had β0/ β+IVS-I-110, and three (17%) had β+IVS-I-110/β+IVS-I-110. As of Jan 30, 2023, all patients enrolled in the long-term follow-up study and the median follow-up was 47·9 months (range 23·8-59·0). All 18 patients were evaluable for transfusion independence, with 16 (89%) of 18 reaching and maintaining transfusion independence to last follow=up (estimated effect size 89·9% [95% CI 65·3-98·6]). All patients had at least one adverse event after beti-cel infusion. There were no serious adverse events considered to be related to beti-cel, and no deaths.

These data demonstrate that beti-cel can allow patients with genotypes that cause severe β-thalassaemia (Both beta null alleles, or the following combinations: beta null plus pathogenic IVSI-100 allele or two pathogenic IVSI-100 allele) to reach transfusion independence. Beti-cel offers the potential to attain near-normal haemoglobin levels for those with severe forms of TDT, and a potentially curative option without the risks and limitations of allogeneic HSPC transplantation. Patients are being followed up for a total of 15 years to assess the durability of transfusion independence and long-term safety profile of beti-cel. (Kwiatkowski, 2024)

CPT/HCPCS:

References:

https://clinicaltrials.gov/ct2/show/NCT03207009?term=03207009&draw=2&rank=1. Accessed 11/16/2022.(2022) Zynteglo. Prescribing Information. https://www.fda.gov/media/160991/download. Accessed 11/16/2022.

Kassim AA, et al.(2024) An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease. Blood. 2024 Jun 20;143(25):2654-2665. doi: 10.1182/blood.2023023301. PMID: 38493482.

Locatelli, F, et al.(2022) Betibeglogene Autotemcel Gene Therapy for Non-ß0/ß0 Genotype ß-Thalassemia. N Engl J Med. 2022 Feb 3;386(5):415-427. doi: 10.1056/NEJMoa2113206. Epub 2021 Dec 11. PMID: 34891223.

Thakar, H.L. et al.(2022) A Study Evaluating the Efficacy and Safety of the LentiGlobin BB305 Drug Product in Participants with Transfusion-Dependent Beta-Thalassemia. Bluebird Bio. https://clinicaltrials.gov/ct2/show/NCT03207009?term=03207009&draw=2&rank=1. Accessed 11/16/2022.

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.