Table 4 Drugs evaluated in normal animals using biomarkers

Same biomarkers (normal animals, animal models, clinical trials)

Eltrombopag olamine^a

Chronic idiopathic thrombocytopenic purpura

Biomarkers

Platelet count

–

Platelet count

True endpoint

–

–

–

Romiplostim^a

Chronic idiopathic thrombocytopenic purpura

Biomarkers

Platelet count

･Platelet count

･Platelet count

True endpoint

–

–

–

Migalastat hydrochloride^a

Fabry disease

Biomarkers

α-Gal A

α-Gal A

GL-3

α-Gal A

GL-3

eGFR

True endpoint

–

–

–

betaine^a

Homocystinuria

Biomarkers

Homocysteine

BHMT

MS

Homocysteine

Homocysteine

True endpoint

–

–

–

lomitapide mesilate^b

Homozygous familial hypercholesterolemia

Biomarkers

VLDL-C + LDL-C

HDL-C

TG

VLDL-C + LDL-C

HDL-C

TG

TC

LDL-C

True endpoint

–

–

–

True endpoints cannot be used in animals (normal and model)

Sodium phenylbutyrate^a

Urea cycle disorders

Biomarkers

Excretion of nitrogen

–

Plasma ammonia

True endpoint

–

–

Hyperammonaemia

Eliglustat tartrate^a

Alleviation of symptoms of Gaucher disease

Biomarkers

Glucosylceramide levels

Glucosylceramide levels

–

True endpoint

–

–

Achieving all the therapeutic goals below

Burosumab^a

FGF23-related hypophosphatemic rickets

osteomalacia

Biomarkers

Serum phosphorus

Urinary phosphate

Calcium

Serum phosphorus

Calcium

Serum Phosphorus

OV/BV

True endpoint

–

–

RGI-C score

Ambrisentan^c

Pulmonary arterial hypertension

Biomarkers

Blood pressure

Blood pressure

–

True endpoint

–

–

6MWD

Riociguat^c

Inoperable CTEPH or postoperative persistent or recurrent CTEPH

Biomarkers

Arterial pressure

Coronary blood flow

Heart rate

The right ventricular systolic pressure

–

True endpoint

–

–

6MWD

Metyrosine^c

Pheochromocytoma

Biomarkers

Noradrenaline

Dopamine

Serotonin

Blood pressure

Systolic pressure

Heart rate

–

True endpoint

–

–

Patients with ≥ 50% decrease in urinary netamephrine 2 fraction

Icatibant acetate^d

Acute oedema attacks caused by hereditary angioedema

Biomarkers

Blood pressure

–

–

True endpoint

–

–

VAS

True endpoints only assessed in disease (animal models and clinical trials)

Fingolimod hydrochloride^a

Multiple sclerosis

Biomarkers

SlP1 receptor

–

–

True endpoint

–

EAE

Recurrence rate

Gd

Miglustat^a

Niemann-Pick disease type C

Biomarkers

Ganglioside

GM1

Ganglioside

–

True endpoint

-

Atactic gait

Survival rate

Eye movement speed

Tetrabenazine^e

Involuntary choreatic movement caused by

Huntington disease

Biomarkers

Dopamine

Noradrenaline

Serotonin

–

–

True endpoint

–

Stereotypy

Motor disturbances

TCS

Natalizumab^e

Multiple sclerosis

Biomarkers

White blood cell

–

–

True endpoint

–

Reducing the incidence of EAE

Prevention of recurrent EAE

Incidence rate of focal

Apomorphine hydrochloride hydrate^e

Parkinson disease

Biomarkers

dopamine

3,4-dihydroxyphenylacetic acid

–

–

True endpoint

–

Increase in angular momentum

UPDRS partIII score

Vigabatrin^e

Epilepsia nutans

Biomarkers

Enzyme inhibitory action

GABA release action

–

–

True endpoint

–

Spasm

Spasm

Rifaximin^f

Hepatic encephalopathy of hyperammonaemia

Biomarkers

NH₃

NH₃

NH₃

True endpoint

–

Survival rate

ED50 of gentamicin

PSE

Catridecacog^g

XIII A-subunit deficiency

Biomarkers

Cross-linked protein

–

–

True endpoint

–

Time to rebleeding

Rate of bleeding