5 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

Date of Approval: 12/19/2017

Indication:

Retinal Dystrophy (Bi-allelic mutation of RPE65)

Disease Rate:

2-3 per 100,000 individuals

Gene Therapy Agent:

LUXTURNA (voretigene neparvovec-rzyl)

Gene Therapy Strategy:

Subretinal injection adeno-associated virus vector-based gene therapy (AAV2)

Side Effects:

Conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), macular hole, subretinal deposits, eye inflammation, eye irritation, eye pain, and maculopathy (wrinkling on the surface of the macula)

6 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

7 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

8 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

9 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

Date of Approval:

05/24/2019

Indication:

Spinal muscular atrophy (pediatric patients < 2 years old with bi-allelic mutations in SMN1)

Disease Rate:

1/10,000 live births

Gene Therapy Agent:

ZOLGENSMA (onasemnogene abeparvovec-xioi)

Gene Therapy Strategy:

In-vivo adeno-associated virus vector-based gene therapy (AAV9)

Side Effects:

Thrombocytopenia, Respiratory insufficiency, thrombotic microangiopathy, Elevated Liver Enzymes, vomiting, elevated troponin-I levels, fevers

10 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

11 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

12 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

13 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

Date of Approval:

08/17/2022

Indication:

Transfusion-dependent

ß-thalassemia

Disease Rate:

Rare in USA (exact number is unknown, estimated that 1,300 people in U.S. are affected)

Gene Therapy Agent:

ZYNTEGLO (betibeglogene autotemcel)

Gene Therapy Strategy:

Ex-vivo Lenti-D lentiviral vector gene therapy (LVV)

Side Effects:

Tachycardia, pain in arm or legs, Alopecia, rash, mucositis, vomiting, abdominal pain, diarrhea, nausea, constipation, leukopenia, thrombopenia

14 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

15 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

16 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

17 of 34

Date of Approval:

09/16/2022

Indication:

Early Cerebral Adrenoleukodystrophy

Disease Rate:

1/10,000 - 1/17,000

Gene Therapy Agent:

SKYSONA (elivaldogene autotemcel)

Gene Therapy Strategy:

Ex-vivo Lenti-D lentiviral vector gene therapy (LVV)

Side Effects:

Tachycardia, Alopecia, pruritus, rash, skin hyperpigmentation, fever, febrile neutropenia, hypertension, transfusion reaction, decreased appetite, anxiety, headache, vision blurred, cough, epistaxis, oropharyngeal pain

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

18 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

19 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

20 of 34

Date of Approval:

11/22/2022

Indication:

Hemophilia B

Disease Rate:

1/25,000 Male Births

Gene Therapy Agent:

HEMGENIX (etranacogene dezaparvovec-drlb)

Gene Therapy Strategy:

In-vivo adeno-associated virus vector-based gene therapy (AAV5)

Side Effects:

Increased Liver Enzymes, headache, hypersensitivity, flu-like symptoms, fatigue, nausea, malaise

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

21 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

22 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

23 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

24 of 34

Date of Approval:

12/16/2022

Indication:

Non-muscle invasive bladder cancer (NMIBC) (unresponsive to BCG treatment)

Disease Rate:

NMIBC incidence =75% of 81,190 estimated newly diagnosed bladder cancer cases in USA. This is about 1/5,000 - 1/6,000.

Gene Therapy Agent:

ADSTILADRIN (nadofaragene firadenovec-vncg)

Gene Therapy Strategy:

In-vivo Intravesical Instillation adeno-associated virus vector-based gene therapy (AAV5)

Side Effects:

Glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination)

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

25 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

26 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

27 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

28 of 34

Date of Approval:

06/30/2023

Indication:

Hemophilia A

Disease Rate:

1/5,000 Male Births

Gene Therapy Agent:

ROCTAVIAN (valoctocogene roxaparvovec-rvox)

Gene Therapy Strategy:

In-vivo adeno-associated virus vector-based gene therapy (AAV5)

Side Effects:

Increased Liver Enzymes, Nausea, fatigue, headache, infusion-related reactions, vomiting, abdominal pain, hepatotoxicity, thromboembolic events.

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

29 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

30 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

31 of 34

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia

32 of 34

Date of Approval:

08/30/2017 (ALL)

Indication:

ALL/DLBCL/FL (in patients that are refractory or in second or later relapse)

Disease Rate:

34 per 1 million (pediatric ALL)

Gene Therapy Agent:

KYMRIAH (tisagenlecleucel)

Gene Therapy Strategy:

Ex-vivo CD19-directed CAR-T cell therapy

Side Effects:

Cytokine release syndrome, infections-pathogen unspecified, hypogammaglobulinemia, fever, decreased appetite, viral infectious disorders, headache, febrile neutropenia, hemorrhage, musculoskeletal pain, vomiting, encephalopathy, diarrhea, hypotension, cough, nausea, bacterial infectious disorders, pain, hypoxia, tachycardia, edema, fatigue, and acute kidney injury

Retinal Degeneration

Spinal Muscular Atrophy

X-linked Adrenoleukodystrophy

Acute Lymphoblastic Leukemia

Hemophilia A

Hemophilia B

Bladder Cancer

Beta-Thalassemia