Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Eliglustat · 11 trials · 8 indications
Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome measure, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported. Baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain during the past 4 weeks at each specified visit. In this outcome measure, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported. Baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
Bone crisis was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crisis, which typically causes periosteal elevation, elevated white blood cell count, fever, or debilitation lasting several days or longer and requires treatment with immobilization of the affected area, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, 2= 2 bone crisis and \>=3 = more than 3 bone crisis during the assessment period. In this outcome measure, number of participants with different bone crises levels at specified time points were reported. Baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
Bone marrow burden (BMB) scores indicate the degree of bone marrow infiltration. BMB score was measured using MRI (magnetic resonance imaging (MRI), ranged from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total BMB score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) to 16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
Bone marrow burden (BMB) scores indicate the degree of bone marrow infiltration was measured using MRI, ranged from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total BMB score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) to 16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement. For this outcome measure, baseline refers to the eliglustat baseline, which was defined as participant's status at the time of first dose of eliglustat in the previous Phase 2 or Phase 3 study.
Bone Mineral Density (BMD) measurements of the spine and bilateral femur were acquired by dual energy X-Ray absorptiometry (DXA) scan. Worst total femur at Baseline refers to the "worst" diseased left or right femur at Baseline. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
BMD measurements of the spine and bilateral femur were acquired by DXA scan. Worst total femur at Baseline refers to the "worst" diseased left or right femur at baseline. For this outcome measure, baseline refers to the eliglustat baseline, which was defined as participant's status at the time of first dose of eliglustat in the previous Phase 2 or Phase 3 study.
BMD measurements of the spine and bilateral femur were acquired by DXA scan. The T-score bone density categories were: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5). Worst total femur at Baseline refers to the "worst" diseased left or right femur at baseline. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
BMD measurements of the spine and bilateral femur were acquired by DXA scan. The T-score bone density categories were: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5). Worst total femur at Baseline refers to the "worst" diseased left or right femur at baseline. For this outcome measure, baseline refers to the eliglustat baseline, which was defined as participant's status at the time of first dose of eliglustat in the previous Phase 2 or Phase 3 study.
BMD measurements of the spine and bilateral femur were acquired by DXA scan. The Z-score bone density categories were: normal (score \>-2) and below normal (score \<=-2). Worst total femur at Baseline refers to the "worst" diseased left or right femur at baseline. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
BMD measurements of the spine and bilateral femur were acquired by DXA scan. The Z-score bone density categories are: normal (score \>-2) and below normal (score \<=-2). Worst total femur at Baseline refers to the "worst" diseased left or right femur at baseline. For this outcome measure, baseline refers to the eliglustat baseline, which was defined as participant's status at the time of first dose of eliglustat in the previous Phase 2 or Phase 3 study.
Osteonecrosis was assessed by bone MRI and X-Ray for spine and by MRI for femur. Total number of new or worsening osteonecrosis events among all the participants with corresponding assessment at specified time points were reported in this outcome measure. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
Fracture was assessed by bone MRI and X-Ray for spine and by MRI for femur. Total number of new or worsening fracture events among all the participants with corresponding assessment at specified time points were reported in this outcome measure. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
Infarcts were assessed by bone MRI and X-Ray for spine and by MRI for femur. Total number of new or worsening infarcts events among all the participants with corresponding assessment at specified time points were reported in this outcome measure. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
Lytic Lesions were assessed by bone X-Ray for spine. Total number of new or worsening lytic lesions events among all the participants with corresponding assessment at specified time points were reported in this outcome measure. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
Observed annual incidence rate was estimated using the total number of events divided by the total years of follow-up in each specified year (for all participants). Osteonecrosis was assessed by bone MRI and X-Ray for spine and by MRI for femur.
Observed annual incidence rate was estimated using the total number of events divided by the total years of follow-up in each specified year (for all participants). Fracture was assessed by bone MRI and X-Ray for spine and by MRI for femur.
Observed annual incidence rate was estimated using the total number of events divided by the total years of follow-up in each specified year (for all participants). Infarcts were assessed by bone MRI and X-Ray for spine and by MRI for femur.
Observed annual incidence rate was estimated using the total number of events divided by the total years of follow-up in each specified year (for all participants). Lytic Lesions were assessed by bone X-Ray for spine.
MIP-1β considered a biomarker of active bone disease, was assayed from plasma. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
MIP-1β considered a biomarker of active bone disease, was assayed from plasma. For this outcome measure, baseline refers to the eliglustat baseline, which was defined as participant's status at the time of first dose of eliglustat in the previous Phase 2 or Phase 3 study.
P1NP, a marker of bone formation was assayed from plasma. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
P1NP, a marker of bone formation was assayed from plasma. For this outcome measure, baseline refers to the eliglustat baseline, which was defined as participant's status at the time of first dose of eliglustat in the previous Phase 2 or Phase 3 study.
CTx, a marker of bone resorption was assayed from plasma. For this outcome measure, baseline refers to the current study baseline, which was defined as status at this study (EFC13781) entry.
CTx, a marker of bone resorption was assayed from plasma. For this outcome measure, baseline refers to the eliglustat baseline, which was defined as participant's status at the time of first dose of eliglustat in the previous Phase 2 or Phase 3 study.
Participants were considered as stable if they met all of the following criteria: 1) no more than 2 bone crisis during PAP (with no more than 1 bone crisis during either the first 6 months or the later 6 months of the period), and were free of other clinically symptomatic bone disease during the entire 52-week PAP; 2) hemoglobin level not decreased \>1.5 g/dL from Baseline for PAP; 3) platelet count not decreased \>25% from Baseline for PAP; 4) spleen volume (in multiples of normal \[MN\]) did not increase \>25% from Baseline for PAP; 5) liver volume (in MN) did not increase \>20% from Baseline for PAP. Baseline for PAP was defined as the last assessment prior to randomization.
Percent change in spleen volume = (\[spleen volume at Week 39 minus spleen volume at baseline\] divided by \[spleen volume at baseline\]) multiplied by 100, where all volumes are in MN.
For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in multiples of normal \[MN\]). Stable hematological parameters were defined as hemoglobin level did not decrease more than (\>) 1.5 gram per deciliter (g/dL) from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume (in MN) did not increase \>20% from baseline.
For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in MN). Stable hematological parameters were defined as hemoglobin level did not decrease \>1.5 g/dL from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume did not increase \>20% from baseline.
A meaningful clinical response was defined as an improvement in at least 2 of the 3 main efficacy parameters: a) an increase in hemoglobin of greater than or equal to (\>=) 0.5 gram/deciliter from baseline, b) an increase in platelets of \>=15 percent (%) from baseline, c) reduction in total spleen volume of \>= 15% from baseline. As hemoglobin, platelets, total spleen volume were abnormal at baseline, within each participant, only those parameters were used in the evaluation of meaningful clinical response which were abnormal at baseline.
Eliglustat after single and repeated doses: Maximum plasma concentration observed (Cmax)
Eliglustat after single and repeated doses: Time to reach Cmax
Eliglustat after single and repeated doses: Area under the plasma concentration versus time curve calculated using the trapezoidal method (AUC0-T)
Eliglustat after single and repeated doses: Area under the plasma concentration versus time curve (AUC)
Maximum plasma concentration observed (Cmax)
Time to reach Cmax (tmax)
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast (AUClast)
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to 2 hours (h) post dose (AUC0-2h)
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 2 hours post dose to 4 hours post dose (AUC2-4h)
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 4 hours post dose to 6 hours post dose (AUC4-6h)
| Arm | Type | Description |
|---|---|---|
| Eliglustat | EXPERIMENTAL | Participants who completed one of the Phase 2 (GZGD00304 \[NCT00358150\]) or Phase 3 studies (GZGD02507 \[NCT00891202\], GZGD02607 \[NCT00943111\], or GZGD03109 \[NCT01074944\]) were enrolled in this current (EFC13781) study. Participants who were cytochrome P450 (CYP) 2D6 intermediate metabolizer (IM), extensive metabolizer (EM) and ultra-rapid metabolizers (URM) received eliglustat 84 milligrams (mg) twice daily and participants who were CYP2D6 poor metabolizer (PM) received eliglustat 84 mg once daily, for duration of minimum 2 years (unless early discontinuation occurred) and up to 4 years, or until commercial eliglustat was available to participants through reimbursement or through the compassionate use (expanded access) program. |
| Twice Daily (BID) Dose Regimen | EXPERIMENTAL | Patients will receive either 50 mg BID or 100 mg BID |
| Once Daily (QD) Dose Regimen | EXPERIMENTAL | Patients will receive either 100 mg QD or 200 mg QD |
| Active | EXPERIMENTAL | Eliglustat |
| Placebo | PLACEBO_COMPARATOR | Placebo |
| Investigational | EXPERIMENTAL | Eliglustat tartrate |
| Imiglucerase | ACTIVE_COMPARATOR | - |
| Eliglustat tartrate | EXPERIMENTAL | - |
| Group 1 | EXPERIMENTAL | CYP2D6 Extensive metabolizers - dose 1, 2 and 3 of eliglustat |
| Group 2 | EXPERIMENTAL | CYP2D6 Poor metabolizers - dose 1, 2 and 3 of eliglustat |
| GZ385660 (healthy subjects) | EXPERIMENTAL | Single dose of eliglustat tartrate will be given under fed conditions |
| GZ385660 (subjects with mild hepatic impairment) | EXPERIMENTAL | Single dose of eliglustat tartrate will be given under fed conditions |
| GZ385660 (subjects with moderate hepatic impairment) | EXPERIMENTAL | Single dose of eliglustat tartrate will be given under fed conditions |
| GZ385660 (subjects with mild renal impairment) | EXPERIMENTAL | Single dose of eliglustat tartrate will be given under fed conditions |
| GZ385660 (subjects with moderate renal impairment) | EXPERIMENTAL | Single dose of eliglustat tartrate will be given under fed conditions |
| GZ385660 (subjects with severe renal impairment) | EXPERIMENTAL | Single dose of eliglustat tartrate will be given under fed conditions |
| Concentration 1 eliglustat in vehicle A | EXPERIMENTAL | Single dose of 5 mL solution held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 1 eliglustat in vehicle B | EXPERIMENTAL | Single dose of 5 mL solution held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 1 eliglustat in vehicle C | EXPERIMENTAL | Single dose of 5 mL solution held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 1 eliglustat in vehicle D | EXPERIMENTAL | Single dose of 5 mL solution held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 1 eliglustat in vehicle E | EXPERIMENTAL | Single dose of 5 mL solution held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 2 eliglustat in vehicle A | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 2 eliglustat in vehicle B | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 2 eliglustat in vehicle C | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 2 eliglustat in vehicle D | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 2 eliglustat in vehicle E | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 3 eliglustat in vehicle A | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 3 eliglustat in vehicle B | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 3 eliglustat in vehicle C | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 3 eliglustat in vehicle D | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Concentration 3 eliglustat in vehicle E | EXPERIMENTAL | Single dose of 5 mL liquid formulation held in the mouth for 15 seconds with swishing but with no ingestion |
| Metoprolol alone then eliglustat + metoprolol | EXPERIMENTAL | In Period 1 all participants will receive a single oral dose of metoprolol 50 mg on Day 1. In Period 2, participants will receive repeat oral doses of eliglustat 150 mg twice a day from Day 3 to Day 8 and a single oral dose of metoprolol 50 mg on Day 7. |
| Name | Type | Description |
|---|---|---|
| Eliglustat, GZ385660 | DRUG | Pharmaceutical form: capsule Route of administration: oral |
| Eliglustat tartrate | DRUG | Oral Capsule in 50 mg or 100 mg dosages |
| Placebo | DRUG | PAP: Matching placebo capsule once daily on Day 1 followed by matching placebo capsule BID from Day 2 through Week 39. LTTP: Participants of the placebo arm in PAP who completed PAP were included in LTTP and received eliglustat tartrate from Day 1 (post Week 39) up to Week 312. Day 1 (post Week 39) was considered as baseline for LTTP. On Day 1, participants received eliglustat tartrate capsule 50 mg BID orally until Week 43 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 47, then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 312. Dose adjustments at Week 43 and Week 47 were based on Genz-99067 trough plasma concentrations (if trough plasma concentration \<5 ng/mL: next higher dose administered; if \>=5 ng/mL: same dose continued) at Week 41 \& Week 45, respectively. |
| Imiglucerase | DRUG | PAP: Imiglucerase intravenous infusion every other week (q2w) up to Week 52 in doses equivalent to participant's past ERT dose prior to any unanticipated treatment interruption, dose reduction, or regimen change. LTTP: Participants originally randomized to imiglucerase received eliglustat tartrate capsule 50 mg BID orally from Week 52+1 Day to Week 56 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 60, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to 5 years. The dose adjustments after Week 56 and Week 60 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was \<5 ng/mL the next higher dose was administered whereas if the Genz-99067 trough plasma concentration was \>=5 ng/mL the same dose was continued. The PK assessment at Week 54 and Week 58 were used for dose adjustment after Week 56 and Week 60, respectively. |
| Eliglustat | DRUG | Pharmaceutical form:Capsule-Route of administration:Oral |
| Metoprolol | DRUG | Tablets for oral administration |
Inclusion criteria : * The participant must have successfully completed the Phase 2 (GZGD00304) or a Phase 3 study (GZGD02507, GZGD02607 or GZGD03109). Successful completion was defined as participants enrolled in one of the above mentioned studies who received eliglustat through the end of the stu...
Eliglustat is an investigational small molecule being developed by Sanofi (SNY) for the treatment of Gaucher disease, specifically Type 1 Gaucher disease. It is currently in Phase 3 clinical development and has not been approved by the FDA.
Eliglustat is a small molecule that targets glucocerebrosidase, an enzyme deficient in Gaucher disease. By inhibiting glucosylceramide synthase, it reduces the accumulation of glucosylceramide, the substrate that builds up in cells of patients with Type 1 Gaucher disease.
Eliglustat is being developed by Sanofi, a multinational pharmaceutical company listed on the stock exchange under the ticker SNY. Sanofi is conducting clinical trials to evaluate the safety and efficacy of Eliglustat for Gaucher disease.
Eliglustat is currently in Phase 3 clinical development for Gaucher disease. It has completed five clinical trials, including a Phase 3 study, and remains an investigational drug that has not yet received FDA approval.
Eliglustat has been studied in several clinical trials, including NCT00358150 (Phase 2), NCT00891202 (Phase 3), NCT06188325 (Phase 1), and NCT06193304 (Phase 1). These trials have evaluated its efficacy, safety, and pharmacokinetics in patients with Gaucher disease and healthy volunteers.
Yes, Eliglustat is also known as Genz-112638, as referenced in the titles of its clinical trials. This alternative name is used in earlier studies, such as NCT00358150 and NCT00891202, to describe the same investigational drug.