Table of Surrogate Endpoints That Were the Basis of Drug Approval or Licensure
What is the purpose of the Surrogate Endpoint Table?
FDA’s surrogate endpoint table provides valuable information for drug developers on endpoints that may be considered and discussed with FDA for individual development programs. This table also fulfills a 21st Century Cures Act requirement to publish a list of “surrogate endpoints which were the basis of approval or licensure (as applicable) of a drug or a biological product” under both accelerated and traditional approval pathways.
Section 3011 of the 21st Century Cures Act established section 507 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which mandates that the FDA publish a list of “surrogate endpoints which were the basis of approval or licensure (as applicable) of a drug or biological product” under both accelerated and traditional approval provisions. The Surrogate Endpoint Table below fulfils this legislative requirement and is intended to provide valuable information for drug developers on endpoints that may be considered and discussed with FDA for individual development programs.
According to section 507(e)(9) of the FD&C Act “[t]he term ‘surrogate endpoint’ means a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure, that is not itself a direct measurement of clinical benefit, and—
‘‘(A) is known to predict clinical benefit and could be used to support traditional approval of a drug or biological product; or
‘‘(B) is reasonably likely to predict clinical benefit and could be used to support the accelerated approval of a drug or biological product in accordance with section 506(c).’’
This surrogate endpoint table includes surrogate endpoints that sponsors have used as primary efficacy clinical trial endpoints for approval of new drug applications (NDAs) or biologics license applications (BLAs). The table also includes surrogate endpoints that may be appropriate for use as a primary efficacy clinical trial endpoint for drug or biologic approval, although they have not yet been used to support an approved NDA or BLA. We believe that this list should facilitate consideration of potential surrogate endpoints when developers are designing their drug development programs.
What are the key considerations of the surrogate endpoint table?
- The table is intended to serve as a reference guide to help inform discussion of potential surrogate endpoints with relevant Center for Biologics Evaluation and Research (CBER) or Center for Drug Evaluation and Research (CDER) review divisions, with the intended goal of facilitating product development.
- The acceptability of these surrogate endpoints for use in a particular drug or biologic development program will be determined on a case-by-case basis. It is context dependent, relying in part on the disease, studied patient population, therapeutic mechanism of action, and availability of current treatments. A particular surrogate endpoint that may be appropriate for use in a particular drug or biologic clinical development program, should not be assumed to be appropriate for use in a different program that is in a different clinical setting.
- The table does not include composite endpoints that are a combination of biomarker surrogate endpoints and clinical endpoints. Likewise, composite endpoints of biomarker surrogate endpoints and clinical outcome assessments are also not included. If a composite endpoint was composed of multiple biomarker surrogate endpoints, that information is included in the table.
- Separate adult and pediatric sections are provided. Pharmacokinetic endpoints that have supported extrapolation from adults to children are not included in the pediatric section.
- If a surrogate endpoint was previously used to support accelerated approval of a drug or biologic but subsequent confirmatory trials failed to demonstrate the expected clinical benefit, the surrogate endpoint would no longer be accepted for this use and it was not included in the table.
What are the table’s limitations?
- This table reflects surrogate endpoints that have either been already used in development programs for drugs that have been approved, or surrogate endpoints that FDA has indicated acceptance of in guidances or other documents. FDA encourages development of novel surrogate endpoints, and strongly encourages sponsors to seek advice from the relevant CBER or CDER division of such novel endpoints early in development by scheduling a PDUFA VI Type C SE meeting to discuss the use of a novel surrogate endpoint in their planned clinical trials. The acceptability of a surrogate endpoint for an individual drug or biologic development program will be determined on a case by case basis.
- The Surrogate Endpoint Table is not a replacement for discussions with appropriate CBER or CDER review divisions. Sponsors are reminded that surrogate endpoints provided in this table are intended to facilitate but not replace discussions of individual drug development programs between the sponsor and the appropriate review division.
- The table does not include surrogate endpoints that may have been accepted for past programs but are no longer acceptable as an endpoint to support registration. As scientific understanding, clinical information, and technology evolve, a previously used surrogate endpoint may no longer be considered sufficiently robust or appropriate for use in current programs.
The SE table will be updated by CBER and CDER every 6 months to reflect current thinking as mandated by section 507 of the FD&C Act.
The Surrogate endpoints are listed in four tables according to their use.
Table Footnotes
# Surrogate endpoint is part of a composite of biomarker surrogate endpoints.
* Mechanism agnostic refers to cases where there are many mechanisms of action associated with a surrogate endpoint, so it is not directly related to a particular causal pathway.
** Defined by a >20% decrease in heart rate or a heart rate <100 bpm or at least intermittent cessation of the arrhythmia
§ Endpoints based on changes in tumor burden may be used for both traditional and accelerated approval depending on context of use, including factors such as disease, effect size, effect duration, residual uncertainty and benefits of other available therapy.
˟ The agency anticipates that this surrogate endpoint could be appropriate for use as a primary efficacy clinical trial endpoint for drug or biologic approval, although it has not yet been used to support an approved NDA or BLA.
¤ Bone mineral density is an acceptable primary endpoint for establishing efficacy for the treatment of male or glucocorticoid-induced osteoporosis after efficacy based on new morphometric vertebral fractures has been established in postmenopausal women.
† Clinical endpoints were required for the approvals.
Downloadable Table of Surrogate Endpoints (XLS - 54 KB)
Table 1. Adult Surrogate Endpoints – Non-Cancer Related
| Disease or Use | Patient Population | Surrogate Endpoint | Type of Approval Appropriate for | Drug Mechanism of Action |
|---|---|---|---|---|
| Acquired Hypofibrinogenemia | Bleeding adults with acquired fibrinogenemia | The total number of allogeneic blood product (ABP) units transfused in the first 24 hours after termination of cardiopulmonary bypass (CPB). | Traditional | Replacement for fibrinogen, a critical soluble plasma protein in the coagulation cascade, is provided |
| Acromegaly | Patients with acromegaly who don't respond to or cannot undergo other standard therapies | Serum Insulin-like growth factor-I (IGF-1) | Traditional | Growth hormone receptor antagonist |
| Acromegaly | Patients with acromegaly who don't respond to or cannot undergo other standard therapies | Serum growth hormone and serum insulin-like growth factor-I (IGF-1) | Traditional | Somatostatin analog |
| Acute Bronchospasm | Patients with acute bronchospasm associated with reversible obstructive airway disease or exercise | Forced expiratory volume in 1 second (FEV1) | Traditional | Beta-2 adrenergic agonist |
| Alzheimer's disease | Patients with mild cognitive impairment or mild dementia stage of Alzheimer's disease | Reduction in amyloid beta plaques | Accelerated | Monoclonal antibody |
| Anthrax vaccine | Persons at high risk of exposure to anthrax | Anti-protective antigen antibody response | Traditional | Induction of immunity |
| Anticoagulation reversal (needed due to life-threatening or uncontrolled bleeding) | Patients treated with a direct or indirect FXa inhibitor when reversal of anticoagulation is needed | Percent change in anti-FXa activity, from baseline to nadir | Accelerated | Binding and sequestering FXa inhibitors |
| Asthma | Patients with asthma | Forced expiratory volume in 1 second (FEV1) | Traditional | Corticosteroid; Beta-2 adrenergic agonist |
| Chronic kidney disease | Patients with chronic kidney disease secondary to multiple etiologies | Estimated glomerular filtration rate or serum creatinine | Traditional | Mechanism agnostic* |
| Chronic obstructive pulmonary disease (COPD) | Patients with COPD | Forced expiratory volume in 1 second (FEV1) | Traditional | Corticosteroid; Long-acting beta2-adrenergic agonist; Anticholinergic; Phosphodiesterase 4 inhibitor |
| COVID-19 and influenza | Individuals 18 through 64 Years of Age | Full-length S-binding IgG (for COVID-19) and Hemagglutination inhibition (HAI) antibodies (for influenza) | Traditional | Induction of antibodies against the S protein of SARS-CoV-2 and the hemagglutinin (HA) protein of influenza virus |
| Cushing's disease | Patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative | Urine free cortisol | Traditional | Somatostatin analog |
| Cushing's syndrome | Patients with endogenous Cushing’s syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery | Urine free cortisol ˟ | Traditional | Cortisol synthesis inhibitor |
| Cystic fibrosis | Patients with cystic fibrosis | Forced expiratory volume in 1 second (FEV1) | Traditional | Cystic fibrosis transmembrane conductance regulator potentiator |
| Cystinuria | Patients with cystinuria | Urinary cystine | Traditional | Reducing and complexing thiol |
| Cytomegalovirus (CMV) | CMV seropositive and hematopoietic transplant recipients requiring prophylaxis | Plasma CMV-DNA exceeding threshold for starting treatment | Traditional | Antiviral |
| Diphtheria vaccine (in combination vaccines) | Persons to be immunized against diphtheria | Anti-diphtheria toxoid antibody | Traditional | Induction of immunity |
| Duchenne muscular dystrophy (DMD) | Patients with DMD who have a confirmed mutation of the DMD gene that is amenable to exon skipping | Skeletal muscle dystrophin | Accelerated | Antisense oligonucleotide |
| Exocrine pancreatic insufficiency | Patients with exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreatectomy, or other conditions | Fecal coefficient of fat absorption | Traditional | Pancreatic enzymes that catalyze the hydrolysis of fats, proteins, and starches. |
| Fabry disease | Patients with confirmed Fabry disease | Complete/near complete clearance of GL-3 inclusions in biopsied renal peritubular capillaries (using the Fabrazyme Scoring System) | Traditional | Enzyme replacement therapy |
| Fabry disease | Patients with confirmed Fabry disease and amenable GLA gene variants | Reduction of GL-3 inclusions in biopsied renal peritubular capillaries (using the BLISS methodology) | Accelerated | Pharmacological chaperone |
| Familial chylomicronemia syndrome | Familial chylomicronemia syndrome | percent change in fasting triglycerides from baseline | Traditional | APOC-III-directed antisense oligonucleotide (ASO) |
| Female hypogonadotropic hypogonadism | Infertile women with hypogonadotropic hypogonadism | Follicle size, serum estradiol and progesterone# | Traditional | Gonadotropin |
| First aid antiseptic; Health care antiseptic; Consumer antiseptic | General public, consumers, and health care professionals | Bacterial count | Traditional and Monograph | Antimicrobial |
| Gout | Patients with gout | Serum uric acid | Traditional | Xanthine oxidase inhibitor; URAT1 inhibitor; Uricase |
| Hepatitis A (Hep A) vaccine | Persons to be immunized against Hep A | Anti-Hep A antigen antibody | Traditional | Induction of immunity |
| Hepatitis B (Hep B) vaccine | Persons to be immunized against Hep B | Anti-Hep B antigen antibody | Traditional | Induction of immunity |
| Hepatitis B Virus (all known subtypes) vaccine | Adults > 18 yo to be immunized against all known suptypes of hepatitis b virus | Neutralizing antibody >/= 10 mIU/mL | Traditional | Induction of antibodies to HBsAg. |
| Hepatitis B Virus (HBV) | Patients with HBV infection with or without cirrhosis | Undetectable plasma HBV-DNA for indefinite treatment or HBsAg loss for finite treatment | Traditional | Antiviral |
| Hepatitis C Virus (HCV) | Patients with HCV infection with or without cirrhosis | Sustained viral response (HCV-RNA) | Traditional | Antiviral |
| Hepatitis D Virus (HDV) | Patients with HDV infection with or without cirrhosis | ≥ 2 log reduction in HDV-RNA plus normalization of ALT or HDV below the LLOQ˟ | Accelerated | Antiviral |
| Hepatorenal syndrome | Patients with hepatorenal syndrome type 1 | Serum creatinine˟ | Traditional | Mechanism agnostic* |
| Homozygous sitosterolemia (phytosterolemia) | Patients with homozygous sitosterolemia (phytosterolemia) | Plasma sitosterol and campesterol | Traditional | Dietary cholesterol absorption inhibitor |
| Human Immunodeficiency Virus-1 (HIV-1) | Patients with HIV-1 | Undetectable plasma HIV RNA | Traditional | Antiviral |
| Human Immunodeficiency Virus-1 (HIV-1) | Patients at high risk of sexually acquired HIV-1 | Serum HIV antibody | Traditional | Antiviral |
| Human Immunodeficiency Virus-1 (HIV-1) | Highly treatment-experienced HIV-1 patients | Greater than 0.5 log reduction in plasma HIV RNA | Traditional | Antiviral |
| Human Papillomavirus | Persons (18 through 45 years of age) to be immunized against human papillomavirus | Cervical intraepithelial neoplasia | Traditional | Induction of immunity |
| Hypercholesterolemia | Patients with heterozygous familial and nonfamilial hypercholesterolemia | Serum LDL cholesterol | Traditional | Lipid-lowering |
| Hypercholesterolemia | Patients with homozygous familial hypercholesterolemia | Serum LDL cholesterol | Traditional | Lipid-lowering |
| Hyperkalemia | Patients with hyperkalemia | Serum potassium | Traditional | Potassium binder |
| Hyperphosphatemia | Dialysis patients with hyperphosphatemia | Serum phosphate | Traditional | Phosphate binder |
| Hypertension | Patients with hypertension | Blood pressure | Traditional | Mechanism agnostic* |
| Hypertriglyceridemia | Patients with severe hypertriglyceridemia | Serum triglycerides | Traditional | Lipid-lowering |
| Hypokalemia | Patients with hypokalemia | Serum potassium | Traditional | Potassium salts |
| Hyponatremia | Patients with hypervolemic and euvolemic hyponatremia | Serum sodium | Traditional | Vasopressin receptor antagonist |
| Hypotension | Patients with distributive shock | Blood pressure | Traditional | Alpha and beta adrenergic agonist; Vasopressin analog |
| Hypothyroidism | Patients with hypothyroidism | Serum thyroid-stimulating hormone (TSH) | Traditional | Thyroid hormone analog |
| Influenza A H5N1 vaccine | Persons to be immunized against influenza | Hemagglutination inhibition antibody | Traditional | Induction of Immunity |
| Influenza vaccine | Persons to be immunized against influenza | Hemagglutination inhibition antibody | Accelerated | Induction of immunity |
| Interoperative hemorrhage | Patients who require reduction of blood pressure to reduce bleeding during surgery | Blood pressure | Traditional | Vasodilator |
| Invasive disease caused by Neisseria meningitidis | Pateint (18-25 years old) with invasive disease caused by Neisseria meningitidis serogroups A, B, C, W, and Y | Serum bactericidal activity (SBA) determined by endogenous complement preserved in the serum samples collected from study participants (enc hSBA) and SBA determined by an exogenous source of human complement (hSBA) | Traditional | Induction of Immunity |
| Invasive disease caused by Streptococcus pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B; and pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B. | Persons to be immunized against S. pneumoniae 18 years of age and older | Opsonophagocytic activity (OPA) | Traditional | Induction of Immunity |
| Invasive pneumococcal disease | Patients with invasive pneumococcal disease | Opsonophagocytosis assay titers | Traditional | Induction of immunity |
| Japanese encephalitis vaccine | Persons to be immunized against Japanese encephalitis | Neutralizing antibody | Traditional | Induction of immunity |
| Lipodystrophy | Patients with congenital or acquired generalized lipodystrophy | Serum hemoglobin A1C, fasting glucose and triglycerides | Traditional | Leptin analog |
| Lupus nephritis | Patients with active lupus nephritis | Complete renal response (CRR), defined as 1) a response in the urine proteinuria (protein-creatine ratio) and 2) preservation/improvement of renal function (estimated glomerular filtration rate) | Traditional | Immunosuppressant |
| Lysosomal Acid Lipase (LAL) deficiency | Patients with LAL deficiency | Serum LDL-c levels | Traditional | Hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme |
| Male hypogonadotropic hypogonadism with inferility | Men with selected cases of hypogonadotropic hypogonadism with inferility | Sperm parameters | Traditional | Gonadotropin |
| Meningococcal (serogroups A, C, Y, W) meningitis vaccine | Persons to be immunized against meningococcal meningitis | Serum bactericidal antibody | Traditional | Induction of Immunity |
| Meningococcal ACYW-135 vaccine | Persons to be immunized against meningococcal meningitis | Serum bactericidal antibody | Traditional | Induction of immunity |
| Meningococcal Group B vaccine | Persons (18 through 25 years of age) to be immunized against meningococcal meningitis | Serum bactericidal antibody | Traditional | Induction of immunity |
| Metabolic dysfunction associated steatohepatitis (MASH) | Precirrhotic NASH patients with liver fibrosis | Histopathologic findings of either 1) resolution of steatohepatitis with no worsening of fibrosis OR 2) improvement of fibrosis with no worsening of steatohepatitis OR 3) Both# | Accelerated | Anti-fibrotic; Anti-inflammatory |
| Methylmalonic acidemia | Patients with acute hyperammonemia due to methylmalonic acidemia | Plasma ammonia | Traditional | Carbamoyl Phosphate Synthetase 1 activator |
| Monkeypox vaccine | Persons to be immunized against monkeypox | Vaccinia-neutralizing antibody | Traditional | Induction of immunity |
| Mycobacterium avium complex (MAC) lung disease | Patients with MAC lung disease | Sputum culture conversion to negative by six months | Accelerated | Antimicrobial |
| N-acetylglutamate Synthase (NAGS) deficiency | Patients with hyperammonemia due to NAGS deficiency | Plasma ammonia | Traditional | Carbamoyl Phosphate Synthetase 1 activator |
| Nonmalignant hematology | Patients with Thrombocytopenia due to immune (idiopathic) thrombocytopenia or chronic hepatitis C | Platelet count response | Traditional | Mechanism agnostic* |
| Nonmalignant hematology | Patients with chronic iron overload or non-transfusion-dependent thalassemia syndromes | Serum ferritin and liver iron concentration | Traditional | Iron chelator |
| Nonmalignant hematology | Patients with anemia due to (1) chronic kidney disease, (2) chemotherapy-induced anemia, (3) zidoviduine in patients with HIV-infection | Hematologic response and reduction in transfusion | Traditional | Mechanism agnostic* |
| Nonmalignant hematology | Patients with severe aplastic anemia | Hematologic response | Traditional | Mechanism agnostic* |
| Nonmalignant hematology | Patients with methemoglobinemia | Serum methemoglobin | Accelerated | Oxidation-reduction agent |
| Nonmalignant hematology | Patients in need of reversal of anticoagulant effects for emergency surgery/urgent procedures and in life-threatening or uncontrolled bleeding. | Change in coagulation parameters | Traditional | Humanized monoclonal antibody fragment |
| Nonmalignant hematology | Patients with sickle cell disease | Hemoglobin response rate | Accelerated | Hemoglobin S polymerization inhibitor |
| Opioid use disorder | Patients with opioid use disorder | Urine toxicology test for opioids | Traditional | 1. Partial opioid agonist 2. Opioid antagonist |
| Osteoporosis | Postmenopausal women with osteoporosis | New morphometric vertebral fractures | Traditional | Estrogen agonist/antagonist; Parathyroid hormone analog; Bisphosphonate; RANK ligand (RANKL) inhibitor |
| Osteoporosis | Patients with glucocorticoid induced osteoporosis | Bone mineral density¤ | Traditional | Bisphosphonate; Parathyroid hormone analog; RANKL inhibitor |
| Osteoporosis | Men with osteoporosis | Bone mineral density¤ | Traditional | Parathyroid hormone analog; Bisphosphonate; RANK ligand (RANKL) inhibitor |
| Paget's disease | Patients with Paget's disease | Serum alkaline phosphatase | Traditional | Bisphosphonate |
| Peri-implantitis | Patients with peri-implantitis | Probing pocket depth ˟ | Traditional | Antimicrobial |
| Periodontitis | Patients with chronic periodontitis with a mean probing pocket depth of greater than 5mm | Probing pocket depth | Traditional | Antimicrobial |
| Pertussis (in combination vaccines) | Persons (18 through 64 years of age) to be immunized against pertussis | Serum antibody concentrations | Traditional | Induction of immunity |
| Phenylketonuria | 1. Patients with hyperphenylalaninemia due to tetrahydrobiopterin-responsive phenylketonuria 2. Adults with PKU who have uncontrolled plasma Phe>600 micromol/L on existing management | Plasma phenylalanine | Traditional | 1. Phenylalanine hydroxylase activator 2. Phenylalanine-metabolizing enzyme |
| Pneumococcal conjugate vaccine | Persons ( ≥ 50 years of age) to be immunized against pneumonia and invasive disease | Opsonophagocytic antibody response | Traditional/Accelerated | Induction of immunity |
| Polio vaccine | Persons to be immunized against polio | Neutralizing antibody response | Traditional | Induction of immunity |
| Polycystic kidney disease | Patients with autosomal dominant polycystic kidney disease with or without associated polycystic liver disease | Total kidney volume ˟ | Accelerated | Mechanism agnostic* |
| Preterm birth | Women with a singleton pregnancy who have a history of singleton spontaneous preterm birth | Delivery prior to 37 weeks gestation | Accelerated | Progesterone analog |
| Primary biliary cholangitis | Patients with primary biliary cholangitis | Serum alkaline phosphatase and bilirubin# | Accelerated | Anti-fibrotic; Anti-inflammatory |
| Primary glomerular diseases associated with significant proteinuria | Patients with primary glomerular disease associated with significant proteinuria | Proteinuria (urinary protein/creatinine ratio) | Accelerated | Mechanism agnostic* |
| Primary hyperoxaluria type 1 (PH1) | Patients with primary hyperoxaluria type 1 (PH1) | Urinary oxalate | Traditional | siRNA against hyroxyacid oxidase 1 gene |
| Primary hyperparathyroidism | Patients with hypercalcemia due to primary hyperparathyroidism | Serum calcium | Traditional | Calcium-sensing receptor agonist |
| Propionic acidemia | Patients with acute hyperammonemia due to propionc acidemia | Plasma ammonia | Traditional | Carbamoyl Phosphate Synthetase 1 activator |
| pulmonary disease | Patients with congenital alpha-1 antitrypsin deficiency | reduction in hepatic fibrosis | Traditional | Alpha-1 protease inhibitor augmentation |
| Pulmonary fibrosis | Patients with pulmonary fibrosis | Forced vital capacity (FVC) | Traditional | Mechanism agnostic* |
| Pulmonary tuberculosis | Patients with active pulmonary tuberculosis | Sputum culture conversion to negative | Accelerated | Antimicrobial |
| Rabies immune globulin | Patients with suspected exposure to a rabid animal | Rabies neutralizing activity and antibody response | Traditional | Passive immunity |
| Rabies Vaccine | Persons to be immunized against rabies | Neutralizing antibody | Traditional | Induction of immunity |
| Respiratory Syncytial Virus, Lower Respiratory Tract Disease | Pateints with Respiratory Syncytial Virus, Lower Respiratory Tract Disease | Neutralizing antibodies to RSV A and B | Traditional | active immunization |
| Secondary hyperparathyroidism associated with chronic kidney disease | Patients with secondary hyperparathyroidism associated with chronic kidney disease | Serum intact parathyroid hormone (iPTH) | Traditional | Calcium-sensing receptor agonist; Vitamin D3 analog |
| Smallpox vaccine | Persons to be immunized against smallpox | Vaccinia-neutralizing antibody | Traditional | Induction of immunity |
| Smallpox vaccine | Persons to be immunized against smallpox | Vaccination site take reaction (replicating smallpox vaccines only) | Traditional | Induction of immunity |
| Supportive cancer care | Patients with delayed methotrexate clearance due to impaired renal function | Plasma methotrexate | Traditional | Carboxypeptidase |
| Supportive cancer care | Patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy expected to result in tumor lysis and subsequent elevation of uric acid | Serum uric acid | Traditional | Uric acid specific enzyme |
| Supportive cancer care | Patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs | Duration of severe neutropenia | Traditional | Leukocyte growth factor |
| Supraventricular tachycardia | adults with supraventricular tachycardia including atrial fibrillation and atrial flutter. | Heart rate ** | Traditional | beta-1 adrenergic receptor antagonist |
| Systemic sclerosis-interstitial lung disease | Patents with systemic sclerosis-interstitial lung disease | Forced vital capacity (FVC) | Traditional | Mechanism agnostic* |
| Testosterone deficiency | Men with primary or hypogonadotropic hypogonadism | Serum testosterone | Traditional | Androgen, GnRH analog |
| Tetanus vaccine | Persons to be immunized against tetanus | Anti-tetanus toxoid antibody | Traditional | Induction of immunity |
| the prevention of disease caused by chikungunya virus (CHIKV) in individuals 18 years of age and older who are at increased risk of exposure to CHIKV | 18 years of age and older who are at increased risk of exposure to CHIKV | CHIKV-specific neutralizing antibody titer ≥150 as determined by micro-plaque reduction neutralization test (μPRNT50) | Accelerated | IXCHIQ elicits CHIKV-specific immune responses. The exact mechanism of protection has not been determined but protection is thought to be mediated by CHIKV-specific neutralizing antibodies. |
| Tick-borne encephalitis vaccine | Persons to be immunized against tick-borne encephalitis | Neutralizing antibody | Traditional | Induction of immunity |
| Tobacco dependence | Cigarette smokers | Exhaled carbon monoxide | Traditional | Smoking cessation |
| Type 1 diabetes mellitus | Patients with type 1 diabetes mellitus | Serum hemoglobin A1C | Traditional | Glucose-lowering |
| Type 1 Gaucher disease | Patients with Type 1 Gaucher disease | Spleen volume, liver volume, hemoglobin and platelet count# | Traditional | Glucosylceramide synthase inhibitor; Hydrolytic lysozomal glucocerebroside-specific enzyme |
| Type 2 diabetes mellitus | Patients with type 2 diabetes mellitus | Serum hemoglobin A1C | Traditional | Glucose-lowering |
| X-linked hypophosphatemia | Patients with X-linked hypophosphatemia | Serum phosphate | Traditional | Fibroblast growth factor 23 inhibitor |
| Yellow fever vaccine | Persons to be immunized against yellow fever | Neutralizing antibody | Traditional | Induction of immunity |
** Defined by a >20% decrease in heart rate or a heart rate <100 bpm or at least intermittent cessation of the arrhythmia
Table 2. Adult Surrogate Endpoints – Cancer Related
| Disease or Use | Patient Population | Surrogate Endpoint | Type of Approval Appropriate for | Drug Mechanism of Action |
|---|---|---|---|---|
| Cancer: hematological malignancies | CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (ALL) | Relapse-free survival (RFS) | Traditional | bispecific CD19-directed CD3 T-cell engager |
| Cancer: hematological malignancies | relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation | complete remission (CR) and CR with partial hematologic recovery (CRh) | Traditional | menin inhibitor |
| Cancer: hematological malignancies | Patients with Acute Lymphoblastic Leukemia | Serum asparaginase | Traditional | Asparagine-specific enzyme |
| Cancer: hematological malignancies | Patients with chronic myeloid leukemia | Major hematologic response | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: hematological malignancies | Patients with acute myeloid leukemia and acute lymphoblastic leukemia | Durable complete remission rate | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: hematological malignancies | Patients with acute lymphoblastic leukemia; myelodysplastic/myeloproliferative diseases; chronic myeloid leukemia | Major hematologic response and cytogenic response | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: hematological malignancies | Patients with B-cell precursor acute lymphoblastic leukemia in first or second complete remission | Minimal residual disease response rate | Accelerated | Mechanism agnostic* |
| Cancer: hematological malignancies | Chronic myelogenous leukemia | Durable major molecular response | Traditional | Mechanism agnostic* |
| Cancer: hematological malignancies | Patients with diffuse large B-cell lymphoma | Event-free survival (EFS) ˟ | Traditional | Mechanism agnostic* |
| Cancer: hematological malignancies | Diffuse large B-Cell lymphoma; hairy cell leukemia; follicular lumphoma | Durable complete response rate | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: hematological malignancies | Patients with multiple myeloma; mantle cell lymphoma; classical Hodgkin lymphoma; follicular lymphoma; B-cell lymphoma; systemic anaplastic large cell lymphoma; chronic myeloid leukemia; chronic lymphocytic leukemia; cutaneous T cell lymphoma; all other non-Hodgkin lymphoma; chronic lymphocyic leukemia; mycosis fungoides | Progression-free survivial (PFS) | Traditional | Mechanism agnostic* |
| Cancer: hematological malignancies | Patients with T-cell lymphoma; B-cell lymphoma; mantle cell lymphoma; classical Hodgkin lymphoma; anaplastic large cell lymphoma and mycosis fungoides; non-Hodgkin lymphoma; multiple myeloma; chronic myeloid leukemia; acute lymphoblastic leukemia; chronic lymphocytic leukemia; accute myeloid leukemia; small lymphocytic lymphoma; Waldenström’s macroglobulinemia; marginal zone lymphoma; follicular lymphoma; light chain amyloidosis | Durable objective overall response rate (ORR) | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: solid tumors | Patients with breast cancer | Pathological complete response | Accelerated | Mechanism agnostic* |
| Cancer: solid tumors | Patients with nonmetastatic castrate-resistant prostate cancer | Metastasis-free survival | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: solid tumors | Patients with advanced prostate cancer | Plasma testosterone levels | Traditional | Gonadotropin-releasing hormone antagonist |
| Cancer: solid tumors | Patients with breast cancer; ovarian cancer; renal cell carcinoma; pancreatic neuroendocrine cancer; colorectal cancer; head and neck cancer; non-small cell lung cancer; melanoma; tuberous sclerosis complex-associated SEGA and renal angiomyolipoma; merkel cell carcinoma; unresectable or metastatic cutaneous basal cell carcinoma; urothelial carcinoma; cervical cancer; endometrial cancer; hepatocellular carcinoma; fallopian tube cancer; microsatellite instability-high cancer; gastric cancer; gastroesophageal junction cancer; thyroid cancer; astrocytoma; Kaposi's sarcoma; unresectable or metastatic cutaneous squamous cell carcinoma; prostate cancer; esophageal cancer; tumor mutational burden high solid tumors; cholangiocarcinoma; bladder cancer; neuroblastoma; mismatch repair deficient solid tumors; unresectable or metastatic HER2-positive (IHC 3+) solid tumors; neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection; neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection; advanced, unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy; solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion; symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity; HER2 positive biliary tract cancer; metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation; unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA antigen(s) A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive, and whose tumor expresses the MAGE-A4 antigen as determined by FDA authorized companion diagnostic devices | Durable objective overall response rate (ORR) | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: solid tumors | Patients with breast cancer; renal cell carcinoma; pancreatic neuroendocrine tumor; soft tissue sarcoma; ovarian, fallopian tube, or primary peritoneal cancer; prostate cancer; thyroid cancer; colorectal cancer; non-small cell lung cancer; head and neck cancer; tuberous sclerosis complex; merkel cell carcinoma; basal cell carcinoma; urothelial carcinoma; cervical cancer; endometrial cancer; hepatocellular carcinoma; fallopian tube cancer; melanoma; astrocytoma; gastrointestinal stromal tumors; Grade 2 oligodendroglioma with a susceptible IDH1 or IDH2 mutation, following surgery including biopsy, sub-total resection, or gross total resection; metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive | Progression-free survivial (PFS) | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: solid tumors | Patients receiving adjuvant therapy following complete surgical resection of colon cancer; colorectal cancer; melanoma; renal cell cancer; gastrointestinal stromal tumor; breast cancer and adjuvant therapy for stage III non-small cell lung cancer | Disease-free survival (DFS) | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: solid tumors | Patients with breast cancer; neuroblastoma | Event-free survival (EFS)˟ | Accelerated/Traditional§ | Mechanism agnostic* |
| Cancer: solid tumors | metastatic colorectal cancer (CRC) with a BRAF V600E mutation | duration of response (DOR) | Accelerated | kinase inhibitor |
Table 3. Pediatric Surrogate Endpoints – Non-Cancer Related
| Disease or Use | Patient Population | Surrogate Endpoint | Type of Approval Appropriate for | Drug Mechanism of Action | Age Range |
|---|---|---|---|---|---|
| Achondroplasia | Patients with achondroplasia | Annualized Growth Velocity | Accelerated | C type natriuretic peptide | 5 years and older |
| Acquired Hypofibrinogenemia | Bleeding children with acquired fibrinogenemia | The total number of allogeneic blood product (ABP) units transfused in the first 24 hours after termination of cardiopulmonary bypass (CPB). | Traditional | Replacement for fibrinogen, a critical soluble plasma protein in the coagulation cascade, is provided | any age |
| Acromegaly | Patients with acromegaly who don't respond to or cannot undergo other standard therapies | Serum Insulin-like growth factor-I (IGF-1) | Traditional | Growth hormone receptor antagonist | 2 years to less than 18 years |
| Acute bronchospasm | Patients with acute bronchospasm associated with reversible obstructive airway disease or exercise | Forced expiratory volume in 1 second (FEV1) | Traditional | Beta-2 adrenergic agonist | 5 years and older |
| Asthma | Patients with asthma | Forced expiratory volume in 1 second (FEV1) | Traditional | Corticosteroid; Beta-2 adrenergic agonist; Anticholinergic | 4 years and older |
| Chagas disease | Patients with Chagas disease | Immunoglobulin G antibody negative or least 20% decrease in optical density on two different IgG antibody tests against antigens of T. cruzi | Accelerated | Antimicrobial | Birth to less than 18 years of age |
| Chronic kidney disease | Patients with chronic kidney disease secondary to multiple etiologies | Estimated glomerular filtration rate or serum creatinine | Traditional | Mechanism agnostic* | |
| Congenital adrenal hyperplasia | congenital adrenal hyperplasia | change in serum androstenedione | Traditional | corticotropin-releasing factor type 1 receptor antagonist | 4 years and older |
| COVID-19 Vaccine | Persons to be immunized against COVID-19 | Neutralizing Antibody | Traditional | Induction of immunity | individuals 12 years of age and older |
| Cystic fibrosis | Patients with cystic fibrosis | Forced expiratory volume in 1 second (FEV1) | Traditional | Cystic fibrosis transmembrane conductance regulator potentiator | 2 years and older |
| Cystinuria | Patients with cystinuria | Urinary/urine cystine | Traditional | Reducing and complexing thiol | |
| Cytomegalovirus (CMV) | CMV seropositive and hemotopoietic transplant recipients requiring prophylaxis | Plasma CMV-DNA exceeding threshold for starting treatment | Traditional | Antiviral | 12 years and older |
| Diphtheria vaccine (in combination vaccines) | Persons to be immunized against diphtheria | Anti-diphtheria toxoid antibody | Traditional | Induction of immunity | 6 weeks and older |
| Diphtheria, tetanus, pertussis, polio, haemophilus type b disease, and hepatitis B vaccine | Patients to be immunized against diphtheria, tetanus, pertussis, polio, haemophilus type b disease, and hepatitis B vaccine | Neutralizing antibody | Traditional | Induction of immunity | 6 weeks to less than 5 years of age |
| Duchenne muscular dystrophy (DMD) | Patients with DMD who have a confirmed mutation of the DMD gene that is amenable to exon skipping | Skeletal muscle dystrophin | Accelerated | Antisense oligonucleotide | 4 years and older |
| Exocrine pancreatic insufficiency | Patients with exocrine pancreatic insufficiency due to cystic fibrosis | Fecal coefficient of fat absorption | Traditional | Pancreatic enzymes that catalyze the hydrolysis of fats, proteins, and starches. | 6 months and older |
| Fabry disease | Patients with confirmed Fabry disease | Complete/near complete clearance of GL-3 inclusions in biopsied renal peritubular capillaries (using the Fabrazyme Scoring System) | Traditional | Enzyme replacement therapy | 2 years and older |
| First aid antiseptic; Health care antiseptic; Consumer antiseptic | General public, consumers, and health care professionals | Bacterial count | Traditional and Monograph | Antimicrobial | All pediatric age groups |
| Haemophilus B conjugate vaccine | Persons to be immunized against Haemophilus B | Anti-polyribosyl-ribitol-phosphate antibody concentrations | Accelerated | Induction of immunity | 6 weeks to 71 months |
| Hepatitis A (Hep A) vaccine | Persons to be immunized against Hep A | Anti-Hep A antigen antibody | Traditional | Induction of immunity | 12 months and older |
| Hepatitis B (Hep B) vaccine | Persons to be immunized against Hep B | Anti-Hep B antigen antibody | Traditional | Induction of immunity | All pediatric age groups |
| Hepatitis B Virus (HCV) | Patients with HBV | Undetectable plasma HBV-DNA for indefinite treatment or HBsAg loss for finite treatment | Traditional | Antiviral | 2 years and older |
| Hepatitis C Virus (HCV) | Patients with HCV with or without cirrhosis | Sustained viral response (HCV-RNA) | Traditional | Antiviral | 3 years and older |
| Homozygous sitosterolemia (phytosterolemia) | Patients with homozygous sitosterolemia (phytosterolemia) | Plasma sitosterol and campesterol | Traditional | Dietary cholesterol absorption inhibitor | |
| Human Immunodeficiency Virus-1 (HIV-1) | Patients with HIV-1 | Undetectable plasma HIV-RNA | Traditional | Antiviral | Patients infected since birth |
| Human Immunodeficiency Virus-1 (HIV-1) | Highly treatment experienced HIV-1 patients | Greater than 0.5 log reduction in plasma HIV RNA | Traditional | Antiviral | Patients infected since birth |
| Human papillomavirus | Persons to be immunized against human papillomavirus | Cervical intraepithelial neoplasia | Traditional | Induction of immunity | 9 through 17 years |
| Hypercholesterolemia | Patients with heterozygous familial hypercholesterolemia | Serum LDL-C | Traditional | Lipid-lowering | |
| Hypercholesterolemia | Patients with homozygous familial hypercholesterolemia | Serum LDL-C | Traditional | Lipid-lowering | |
| Hyperkalemia | Patients with hyperkalemia | Serum potassium | Traditional | Potassium binder | |
| Hyperphosphatemia | Patients with chronic kidney disease on dialysis with hyperphosphatemia | Serum phosphate | Traditional | Phosphate binder | 9 years and older |
| Hypertension | Patients with hypertension | Blood pressure | Traditional | Mechanism agnostic* | |
| Hypokalemia | Patients with hypokalemia | Serum potassium | Traditional | Potassium salts | |
| Hyponatremia | Patients with hypervolemic and euvolemic hyponatremia | Serum sodium | Traditional | Vasopressin receptor antagonist | |
| Hypothyroidism | Patients with hypothyroidism | Thyroid-stimulating hormone (TSH) | Traditional | Thyroid hormone analog | |
| Influenza A H5N1 | Persons to be immunized against influenza | Hemagglutination inhibition antibody | Traditional | Induction of Immunity | 6 months and older |
| Influenza vaccine | Persons to be immunized against influenza | Hemagglutination inhibition antibody | Accelerated | Induction of immunity | 6 months and older |
| Invasive disease caused by Neisseria meningitidis | Pediatric pateint (10 years) with invasive disease caused by Neisseria meningitidis serogroups A, B, C, W, and Y | Serum bactericidal activity (SBA) determined by endogenous complement preserved in the serum samples collected from study participants (enc hSBA) and SBA determined by an exogenous source of human complement (hSBA) | Traditional | Induction of Immunity | 10 years and older |
| Japanese encephalitis vaccine | Persons to be immunized against Japanese encephalitis | Neutralizing antibody | Traditional | Induction of immunity | 2 months and older |
| Lipodystrophy | Patients with congenital or acquired generalized lipodystrophy | Serum hemoglobin A1C , fasting glucose and triglycerides | Traditional | Leptin analog | |
| Lysosomal Acid Lipase (LAL) deficiency | Patients with LAL deficiency | Serum LDL-c levels | Traditional | Hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme | Birth to less than 18 years of age |
| Meningococcal (serogroups A, C, Y, W) meningitis vaccine | Persons to be immunized against meningococcal meningitis | Serum bactericidal antibody | Traditional / Accelerated | Induction of Immunity | 2 years and older |
| Meningococcal A C Y W-135 vaccine | Persons to be immunized against meningococcal meningitis | Serum bactericidal antibody | Traditional | Induction of immunity | 2 months and older |
| Meningococcal B vaccine | Persons to be immunized against meningococcal meningitis | Serum bactericidal antibody | Traditional / Accelerated | Induction of immunity | 10 to 25 years |
| Methylmalonic acidemia | Patients with acute hyperammonemia due to methylmalonic acidemia | Plasma ammonia | Traditional | Carbamoyl Phosphate Synthetase 1 activator | Birth to less than 18 years of age |
| N-acetylglutamate Synthase (NAGS) deficiency | Patients with hyperammonemia due to NAGS deficiency | Plasma ammonia | Traditional | Carbamoyl Phosphate Synthetase 1 activator | Birth to less than 18 years of age |
| Nonmalignant hematology | Patients with thrombocytopenia due to immune (idiopathic) thrombocytopenia or chronic hepatitis C | Platelet count | Traditional | Thrombopoietin receptor agonist | 1 year and older |
| Nonmalignant hematology | 2 years or older for chronic iron overload and 10 years older for non-transfusion-dependent thalassemia syndromes | Serum ferritin and liver iron concentration | Traditional§ | Iron chelator | 2 years or older for chronic iron overload and 10 years older for non-transfusion-dependent thalassemia syndromes |
| Nonmalignant hematology | Patients with severe aplastic anemia | Hematologic response | Traditional | Thrombopoietin receptor agonist | 1 year and older |
| Nonmalignant hematology | Patients with methemoglobinemia | Serum methemoglobin | Accelerated | Oxidation-reduction agent | All pediatric age groups |
| Nonmalignant hematology | Patients with sickle cell disease | Hemoglobin response rate | Accelerated | Hemoglobin S polymerization inhibitor | 4 years and older |
| Pertussis (in combination vaccines) | Persons to be immunized against pertussis | Serum antibody concentrations | Traditional | Induction of immunity | 6 weeks and older |
| Phenylketonuria | Patients with hyperphenylalaninemia due to tetrahydrobiopterin-responsive phenylketonuria | Plasma phenylalanine | Traditional | Phenylalanine hydroxylase activator | 1 month to less than 18 years of age |
| Polio vaccine | Persons to be immunized against polio | Neutralizing antibody | Traditional | Induction of immunity | 6 weeks and older |
| Precocious puberty | Patients with central precocious puberty | Serum luteinizing hormone | Traditional | Gonadotropin releasing hormone (GnRH) agonist | |
| Prevention of disease caused by chikungunya virus (CHIKV) | Individuals 12 years of age and older who are at increased risk of exposure to CHIKV | CHIKV specific neutralizing antibody (a NT80 titer of ≥100 was determined to be reasonably likely to predict clinical benefit) | Accelerated | The exact mechanism of protection has not been determined. VIMKUNYA elicits CHIKV specific immune responses. | 12 years and older |
| Primary glomerular diseases associated with significant proteinuria | Patients with primary glomerular disease associated with significant proteinuria | Proteinuria (urinary protein/creatinine ratio) ˟ | Accelerated | Mechanism agnostic* | |
| Primary hyperoxaluria type 1 (PH1) | Patients with primary hyperoxaluria type 1 (PH1) | Urinary oxalate | Traditional | siRNA against hyroxyacid oxidase 1 gene | |
| Propionic acidemia | Patients with acute hyperammonemia due to propionc acidemia | Plasma ammonia | Traditional | Carbamoyl Phosphate Synthetase 1 activator | Birth and older |
| Pulmonary Arterial Hypertension | Patients with PAH | Pulmonary vascular resistance | Traditional | Endothelin receptor antagonist | Any age children if there is an approved use in adults and the drug lowers PVR in adults. |
| Pulmonary Tuberculosis (TB) | Patients with active pulmonary tuberculosis | Sputum culture conversion to negative | Accelerated | Antimicrobial | 5 years and older |
| Rabies immune globulin | Patients with suspected exposure to a rabid animal | Rabies neutralizing activity and antibody response | Traditional | Passive immunity | |
| Rabies vaccine | Persons to be immunized against rabies | Neutralizing antibody | Traditional | Induction of immunity | All pediatric age groups |
| Secondary hyperparathyroidism associated with chronic kidney disease | Patients with secondary hyperparathyroidism associated with chronic kidney disease | Serum intact parathyroid hormone (iPTH) | Traditional | Vitamin D analog | |
| steroid-refractory acute graft versus host disease (SR-aGvHD) | Pediatric patients 2 months of age and older with steroid-refractory acute graft versus host disease (SR-aGvHD) | Overall response rate (ORR) | Traditional | The mechanism of action is not clear but may be related to immunomodulatory effects. | 2 months and older |
| Tetanus vaccine (alone or in combination vaccines) | Persons to be immunized against tetanus | Anti-tetanus toxoid antibody | Traditional | Induction of Immunity | 6 weeks and older |
| Tick-borne encephalitis vaccine | Persons to be immunized against tick-borne encephalitis | Seropositivity by neutralization test | Traditional | Induction of TBEV-neutralizing antibodies | 1 year and older |
| Type 1 diabetes mellitus | Patients with type 1 diabetes mellitus | Serum hemoglobin A1C | Traditional | Glucose-lowering | 6 to 15 years |
| Type 1 Gaucher disease | Patients with type 1 Gaucher disease | Spleen volume, liver volume, hemoglobin and platelet count# | Traditional | Hydrolytic lysozomal glucocerebroside-specific enzyme | 2 to 17 years |
| Type 2 diabetes mellitus | Patients with type 2 diabetes mellitus | Serum hemoglobin A1C | Traditional | Glucose-lowering | 10 to 18 years |
| X-linked hypophosphatemia | Patients with X-linked hypophosphatemia | Serum phosphate | Traditional | Fibroblast growth factor 23 inhibitor | 1 year and older |
| Yellow fever vaccine | Persons to be immunized against yellow fever | Neutralizing antibody | Traditional | Induction of immunity | 9 months and older |
Table 4. Pediatric Surrogate Endpoints – Cancer Related
| Disease or Use | Patient Population | Surrogate Endpoint | Type of Approval Appropriate for | Drug Mechanism of Action | Age Range |
|---|---|---|---|---|---|
| Cancer: hematological malignancies | relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation | complete remission (CR) and CR with partial hematologic recovery (CRh) | Traditional | menin inhibitor | 1 year and older |
| Cancer: hematological malignancies | Patients with acute lymphoblastic leukemia; B-cell lymphoma | Durable objective overall response rate (ORR) | Accelerated/Traditional§ | Mechanism agnostic* | 1 to 21 years |
| Cancer: hematological malignancies | Patients with acute lymphoblastic leukemia | Event-free Survival | Accelerated/Traditional§ | Mechanism agnostic* | 1 to 21 years |
| Cancer: hematological malignancies | Patients with chronic myeloid leukemia | Major hematologic and cytogenic response | Accelerated/Traditional§ | Mechanism agnostic* | 3 to 20 years |
| Cancer: hematological malignancies | Patients with Acute Lymphoblastic Leukemia | Serum Asparaginase | Traditional | Asparagine-specific enzyme | All pediatric age groups |
| Cancer: solid tumors | Patients with tuberous sclerosis complex with subependymal giant cell astrocytoma; merkel cell carcinoma; thyroid cancer; tumor mutational burden high solid tumors; neuroblastoma, neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection; solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion | Durable objective overall response rate (ORR) | Accelerated | Mechanism agnostic* | 28 days and older |
| Cancer: solid tumors | Patients with metastatic melanoma; Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation, following surgery including biopsy, sub-total resection, or gross total resection | Progression-free survival(PFS) | Accelerated | Mechanism agnostic* | 12 years and older |
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