Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Venglustat
GZ/SAR402671 · 7 trials · 5 indications
Criteria for potentially clinically significant abnormalities: * Hemoglobin: less than or equal to (\<=) 115 grams per liter (g/L); greater than or equal to (\>=)185 g/L; decreased from baseline (DFB) \>=20 g/L * Hematocrit: \<=0.37 volume/volume (v/v); \>=0.55 v/v * Erythrocytes: \>=6 Tera/L * Platelets: lesser than (\<) 100 Giga/L; \>=700 Giga/L * Leukocytes: \<3.0 Giga/L (Non-Black \[NB\]) or \<2.0 Giga/L (Black \[B\]); \>=16.0 Giga/L * Neutrophils: \<1.5 Giga/L (NB) or \<1.0 Giga/L (B); * Lymphocytes: greater than (\>) 4.0 Giga/L * Monocytes: \>0.7 Giga/L * Basophils: \>0.1 Giga/L * Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L) For this analysis, baseline was defined as initial ACT13739 study baseline.
Criteria for potentially clinically significant abnormalities: * Sodium: \<=129 millimoles (mmol)/L; \>=160 mmol/L * Potassium: \<3 mmol/L; \>=5.5 mmol/L * Chloride: \<80 mmol/L; \>115 mmol/L.
Criteria for potentially clinically significant abnormalities: * Alanine Aminotransferase (ALT): \>3 ULN; \>5 ULN; \>10 ULN and \>20 ULN * Aspartate aminotransferase (AST): \>3 ULN; \>5 ULN; \>10 ULN and \>20 ULN * Alkaline phosphatase: \>1.5 ULN * Bilirubin: \>1.5 ULN; \>2 ULN.
Criteria for potentially clinically significant abnormalities: * Glucose: \<=3.9 mmol/L and \< lower limits of normal (LLN); \>=11.1 mmol/L (unfasted \[unfas\]) or \>=7 mmol/L (fasted \[fas\]) * Lipase: \>= 3 ULN * C Reactive Protein (CRP): \> 2 ULN or \> 10 milligrams (mg)/L (if ULN not provided).
Criteria for potentially clinically significant abnormalities: * Creatinine: \>=150 micromoles per liter (mcmol/L) (Adults); \>=30% change from baseline; \>= 100% change from baseline * Blood urea nitrogen: \>=17 mmol/L * Urate: \<120 mcmol/L; \>408 mcmol/L For this analysis, baseline was defined as initial ACT13739 study baseline.
Criteria with potentially clinically significant urine abnormalities: pH: \<= 4.6; pH: \>= 8.0
Criteria for potentially clinically significant vital sign abnormalities: * Systolic blood pressure (SBP) supine: \<=95 millimeters of mercury (mmHg) and DFB \>=20 mmHg; \>=160 mmHg and increase from baseline (IFB) \>=20 mmHg * Diastolic blood pressure (DBP) supine: \<=45 mmHg and DFB \>=10 mmHg; \>=110 mmHg and IFB \>=10 mmHg * Heart rate (HR) supine: \<=50 beats per minute (bpm) and DFB \>=20 bpm; \>=120 bpm and IFB \>=20 bpm * Weight: \>=5% DFB; \>=5% IFB For this analysis, baseline was defined as initial ACT13739 study baseline.
Criteria for potentially clinically significant ECG abnormalities: * ECG mean HR: \<30 bpm; \<30 bpm and DFB \>=20 bpm; \<40 bpm; \<40 bpm and DFB \>=20 bpm; \<50 bpm; \<50 bpm and DFB \>=20 bpm; \>90 bpm; \<90 bpm and DFB \>=20 bpm; \>100 bpm; \<100 bpm and DFB \>=20 bpm; \>120 bpm; \<120 bpm and DFB \>=20 bpm * PR Interval: \>200 milliseconds (ms); \>200 ms and IFB \>=25%; \>220 ms; \>220 ms and IFB \>=25%; \>240 ms; \>240 ms and IFB \>=25% * QRS duration: \>110 ms; \>110 ms and IFB \>=25%; \>120 ms; \>120 ms and IFB \>=25% * QTc Bazett (QTcB) interval: \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms, IFB \>60 ms * QTc Fridericia (QTc F): \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms * QT Interval: \>500 ms For this analysis, baseline was defined as initial ACT13739 study baseline.
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Change from Baseline in GL-3 score was obtained by subtracting Baseline value from post-baseline value at Week 26. A negative change from Baseline indicates less severe condition at Week 26.
| Arm | Type | Description |
|---|---|---|
| Venglustat | EXPERIMENTAL | Participants will receive venglustat once daily, orally |
| Standard of Care Therapy | ACTIVE_COMPARATOR | Participants will receive a locally approved Fabry therapy at the standard dose and schedule (in accordance with the locally approved prescribing information) |
| Cerezyme | ACTIVE_COMPARATOR | Cerezyme |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo once daily for 12 months |
| Open label (OL) venglustat | EXPERIMENTAL | Administered once a day orally for up to approximately 10 years. Participants will continue their usual dose of Cerezyme during Part 1, Part 2 and Part 3. There is no administration of Cerezyme in Part 4 unless administrated as rescue treatment. |
| GZ/SAR402671 | EXPERIMENTAL | Participants received GZ/SAR402671 15 milligrams (mg) once daily orally for 30 months in this extension study (LTS14116). |
| Participants with mild hepatic impairment | EXPERIMENTAL | Venglustat single dose on Day 1 |
| Participants with normal hepatic function | EXPERIMENTAL | Venglustat single dose on Day 1 |
| Participants with moderate hepatic impairment | EXPERIMENTAL | Venglustat single dose on Day 1 |
| Participants with severe hepatic impairment | EXPERIMENTAL | Venglustat single dose on Day 1 |
| Name | Type | Description |
|---|---|---|
| Venglustat (GZ402671) | DRUG | Tablet; Oral |
| Agalsidase alfa | DRUG | Concentrate for solution for infusion; IV infusion |
| Agalsidase beta (GZ419828) | DRUG | Powder for concentrate for solution for infusion; IV infusion |
| Migalastat | DRUG | Hard capsules; Oral |
| Venglustat | DRUG | tablet; oral |
| imiglucerase | DRUG | sterile lyophilized product; intravenous |
| Placebo | DRUG | Pharmaceutical form: Tablet Route of administration: Oral |
| GZ/SAR402671 | DRUG | Pharmaceutical form:capsule Route of administration: oral |
Inclusion Criteria: * Male and female participants aged 18 to 65 with previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease. * Participants may be receiving treatment with agalsidase alfa, agalsidase beta, or migalastat, or may be untreated. * Left vent...
GZ/SAR402671 is an investigational small molecule being developed for Fabry disease, a rare genetic disorder. It is intended for treatment-naive adult male patients with Fabry disease. The drug is currently in Phase 2 clinical development and is not approved by regulatory authorities.
GZ/SAR402671 is being developed by Sanofi, a multinational pharmaceutical company traded on the stock exchange under the ticker SNY. Sanofi is conducting clinical trials to evaluate the safety and efficacy of this investigational drug for Fabry disease.
GZ/SAR402671 is in Phase 2 clinical development. Two Phase 2 trials have been completed, with a total of 19 participants enrolled. The drug remains investigational and has not received regulatory approval for Fabry disease.
GZ/SAR402671 has been studied in two completed Phase 2 trials: NCT02228460, which evaluated safety, pharmacodynamics, pharmacokinetics, and exploratory efficacy in 11 treatment-naive adult male patients, and NCT02489344, a long-term follow-up study in 8 patients. Both trials were conducted in the United States, France, Poland, Russia, and the United Kingdom.
Yes, GZ/SAR402671 and SAR402671 refer to the same investigational drug. The compound is being developed by Sanofi for Fabry disease and has been evaluated in Phase 2 clinical trials. It is a small molecule intended for treatment-naive adult male patients.