Risdiplam

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H23N7O
Molecular Weight	401.4643
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CN2N=C(C=C(C)C2=N1)C3=CC(=O)N4C=C(C=CC4=N3)N5CCNC6(CC6)C5

InChI

InChIKey=ASKZRYGFUPSJPN-UHFFFAOYSA-N

InChI=1S/C22H23N7O/c1-14-9-18(26-29-11-15(2)24-21(14)29)17-10-20(30)28-12-16(3-4-19(28)25-17)27-8-7-23-22(13-27)5-6-22/h3-4,9-12,23H,5-8,13H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C22H23N7O
Molecular Weight	401.4643
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213535s003s005lbl.pdf

Risdiplam (Evrysdi™) is an orally administered, survival motor neuron 2 (SMN2)-directed RNA splicing modifier being developed by Roche, PTC Therapeutics Inc and the SMA Foundation for the treatment of the spinal muscular atrophy. The small molecule is designed to treat spinal muscular atrophy caused by mutations in chromosome 5q leading to SMN protein deficiency. Using in vitro assays and studies in transgenic animal models of SMA, risdiplam was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein in the brain. The drug boosts the ability of an alternative gene SMN2 to produce full-length and functional SMN protein. In August 2020, Evrysdi™ (risdiplam) received its first approval in the USA for the treatment of spinal muscular atrophy in patients 2 months of age and older.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
SMN2 pre-mRNA 1 Target ID: CHEMBL3826841 Sources: https://www.ema.europa.eu/en/documents/assessment-report/evrysdi-epar-public-assessment-report_en.pdf	Modulator 846		12.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Spinal muscular atrophy 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213535s003s005lbl.pdf	Primary		Approved 8583	EVRYSDI Approved Use Indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients. Launch Date 2020

C_max

Value	Dose	Analyte	Population
73.3 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
178 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	0.25 mg/kg 1 times / day steady-state, oral dose: 0.25 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
134 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
60 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	0.08 mg/kg 1 times / day steady-state, oral dose: 0.08 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
117 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	0.2 mg/kg 1 times / day steady-state, oral dose: 0.2 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
114 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	0.25 mg/kg 1 times / day steady-state, oral dose: 0.25 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
2.82 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	0.6 mg single, oral dose: 0.6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.33 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
24.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
93.2 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
24.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=21	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
24.8 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=21	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
25.9 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
78.6 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
42.6 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
113 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1440 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2286 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	0.25 mg/kg 1 times / day steady-state, oral dose: 0.25 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
1943 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
1060 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	0.08 mg/kg 1 times / day steady-state, oral dose: 0.08 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
1930 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	0.2 mg/kg 1 times / day steady-state, oral dose: 0.2 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
1770 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=15	0.25 mg/kg 1 times / day steady-state, oral dose: 0.25 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
86.7 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	0.6 mg single, oral dose: 0.6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
294 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1080 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3290 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1080 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=21	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1010 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=21	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
404 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1250 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
613 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1730 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	8 mg 1 times / day multiple, oral dose: 8 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
24.8 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	0.6 mg single, oral dose: 0.6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
40.1 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
47.7 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
68.7 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=20	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
68.7 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=21	6 mg single, oral dose: 6 mg route of administration: Oral experiment type: SINGLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
50 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
50 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=25	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RISDIPLAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
11% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000PharmR.pdf#page=5 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf#page=10			RISDIPLAM plasma	Homo sapiens

Doses

Dose	Population	Adverse events
5 mg 1 times / day steady, oral Recommended\|Highest studied dose Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf	unhealthy, NEWBORN\|CHILD Health Status: unhealthy Age Group: NEWBORN\|CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf	Disc. AE: Gastroenteritis, Constipation... AEs leading to discontinuation/dose reduction: Gastroenteritis (1 patient) Constipation (1 patient) Pyrexia (1 patient) Aspiration (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf

AEs

AE	Significance	Dose	Population
Aspiration	1 patient Disc. AE	5 mg 1 times / day steady, oral Recommended\|Highest studied dose Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf	unhealthy, NEWBORN\|CHILD Health Status: unhealthy Age Group: NEWBORN\|CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf
Constipation	1 patient Disc. AE	5 mg 1 times / day steady, oral Recommended\|Highest studied dose Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf	unhealthy, NEWBORN\|CHILD Health Status: unhealthy Age Group: NEWBORN\|CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf
Gastroenteritis	1 patient Disc. AE	5 mg 1 times / day steady, oral Recommended\|Highest studied dose Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf	unhealthy, NEWBORN\|CHILD Health Status: unhealthy Age Group: NEWBORN\|CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf
Pyrexia	1 patient Disc. AE	5 mg 1 times / day steady, oral Recommended\|Highest studied dose Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf	unhealthy, NEWBORN\|CHILD Health Status: unhealthy Age Group: NEWBORN\|CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946 inducer 1087	inducer 440 inhibitor 2438	inhibitor 2507 inducer 109	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MATE1 415 MATE2-K 77 CYP1A2 2153 OATP1B1 1079 CYP3A5 136 OAT3 747 CYP2C19 2057 CYP2B6 926 OATP1B3 961 CYP2C8 1057 OCT2 779 OAT1 725 BCRP 910 P-gp 1741	FMO1 25 P-gp 2052 CYP3A7 109 CYP2J2 71 CYP1A1 389 FMO3 77 BCRP 697	CYP2C8 198 CYP2C19 329 CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP2D6 2546	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 10.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8.0	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 10.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 11 \| 16 \| 22 \| 26	no	no (co-administration study) Comment: No clinically relevant effects on midazolam exposure (increased Cmax and AUCinf by 1.16-fold and 1.08 foold) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 11 \| 16 \| 22 \| 26
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22 \| 26	no	no (co-administration study) Comment: No clinically relevant effects on midazolam exposure (increased Cmax and AUCinf by 1.16-fold and 1.08 fold) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 8 \| 22 \| 26
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 5 \| 8 \| 23	yes [IC50 0.09 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 5 \| 8 \| 23	yes [IC50 0.15 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
FMO1 25	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 6 \| 7	major
FMO3 77	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 6 \| 7	major
CYP1A1 389	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 6 \| 7	minor
CYP2J2 71	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 6 \| 7	minor
CYP3A7 109	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 6 \| 7	minor
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 6 \| 7 \| 8 \| 24	minor	no (co-administration study) Comment: Itraconazole did not cause clinically relevant interactions (GMR Cmax and AUC120 were 0.906 and 1.11). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 6 \| 7 \| 8 \| 24
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 10.0	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000ClinPharmR.pdf Page: 10 \| 22	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213535Orig1s000PharmR.pdf Page: 5 \| 14

PubMed

Title	Date	PubMed
How does risdiplam compare with other treatments for Types 1-3 spinal muscular atrophy: a systematic literature review and indirect treatment comparison.	2022-04	35040693
Risdiplam: A Review in Spinal Muscular Atrophy.	2022-04	35284988
Risdiplam in Type 1 Spinal Muscular Atrophy.	2021-03-11	33626251
Risdiplam: First Approval.	2020-11	33044711

Patents

Sample Use Guides

In Vivo Use Guide

EVRYSDI is administered orally once daily. The recommended dosage is determined by age and body weight. 2 years of age and older weighing 20 kg or more: 5 mg

Route of Administration: Oral

In Vitro Use Guide

At clinically relevant concentrations (Cmax of 37 nM unbound risdiplam in infants with type 1 SMA aged 1-7 months at enrolment), risdiplam efficiently corrected the dysfunctional splicing of the human SMN2 pre-mRNA by shifting the alternative splicing reaction towards the inclusion of SMN2 exon 7 and by inducing gene expression of FL SMN2 mRNA, in cultured Type 1 SMA patient-derived cells (EC50 11-12 nM and 24-19 nM, respectively); this in turns led to the production of the FL mRNA which translated into increased SMN protein levels (EC50 12 nM).

Substance Class	Chemical Created by `admin` on `Wed Apr 02 10:07:13 GMT 2025` Edited by `admin` on `Wed Apr 02 10:07:13 GMT 2025`
Record UNII	76RS4S2ET1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RG-7916

Preferred Name

English

Risdiplam

Official Name

English

RO-7034067

Code

English

RO7034067

Code

English

RISDIPLAM [USAN]

Common Name

English

RG7916

Code

English

EVRYSDI

Brand Name

English

RISDIPLAM [JAN]

Common Name

English

Risdiplam [WHO-DD]

Common Name

English

RISDIPLAM [ORANGE BOOK]

Common Name

English

RISDIPLAM [MI]

Common Name

English

risdiplam [INN]

Common Name

English

(7-(4,7-DIAZASPIRO(2.5)OCTAN-7-YL)-2-(2,8-DIMETHYLIMIDAZO(1,2-B)PYRIDAZIN-6-YL)PYRIDO(1,2-A)PYRIMIDIN-4-ONE

Systematic Name

English

4H-PYRIDO(1,2-A)PYRIMIDIN-4-ONE, 7-(4,7-DIAZASPIRO(2.5)OCT-7-YL)-2-(2,8-DIMETHYLIMIDAZO(1,2-B)PYRIDAZIN-6-YL)-

Systematic Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/19/2145