Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Tolebrutinib · 10 trials · 8 indications
Potentially clinically significant abnormalities (PCSAs) determined by laboratory tests, electrocardiogram (ECG), or vital signs and safety findings on MRI during the study period.
The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal \[motor\], cerebellar \[coordination\], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Time to onset of 6-month CDP was defined as the time from randomization to the onset of a sustained increase from baseline in EDSS score of \>=1.0 point from the baseline EDSS score when the baseline score was \<=5.0 or of \>=0.5 points when the baseline EDSS score was \>5.0 confirmed after a minimum 6-month interval.
Time to onset of 6-month cCDP defined as follows: Increase over at least 6 months of ≥1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is ≤5.5, or ≥0.5 points when the baseline EDSS score is \>5.5, or ≥20% from the baseline T25-FW, or ≥20% from the baseline 9-HPT
Multiple sclerosis (MS) relapse was defined as a monophasic, acute or subacute onset of new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Symptoms were attributable to MS, lasted for \>=24 hours with or without recovery, present at normal body temperature, and preceded by \>=30 days of clinical stability.
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the respective on-treatment periods.
Area under the plasma concentration (AUC) versus time curve extrapolated to infinity
AUC up to the last measurable concentration
Area under the curve, reflects the concentration of drug
| Arm | Type | Description |
|---|---|---|
| Tolebrutinib | EXPERIMENTAL | * Participants will receive OL tolebrunitib 60 mg once daily. * RMS participants who are not eligible for OL tolebrutinib per Health Authority and/or ethics committee decisions on the study conduct (ie, partial hold on initiation of tolebrutinib) will continue their parent study treatment assignment as per their randomization from the parent study. |
| Teriflunomide | ACTIVE_COMPARATOR | * participants will receive teriflunomide 14 mg daily * RMS participants who are not eligible for OL tolebrutinib per Health Authority and/or ethics committee decisions on the study conduct (ie, partial hold on initiation of tolebrutinib) will continue their parent study treatment assignment (either tolebrutinib or teriflunomide) as per their randomization from the parent study. If unblinded to teriflunomide parent study treatment assignment, these RMS participants will continue teriflunomide in the LTS17043 study. |
| SAR442168 | EXPERIMENTAL | 60 mg of oral SAR442168 once daily |
| Placebo | PLACEBO_COMPARATOR | Placebo tablet to match SAR442168 once daily |
| Mild hepatic impairment group | EXPERIMENTAL | Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition |
| Normal hepatic function group | EXPERIMENTAL | Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition |
| Severe Renal Impairment (RI) group (Part A only) | EXPERIMENTAL | Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition |
| Normal Renal Function group (Part A and B) | EXPERIMENTAL | Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition |
| Moderate RI group (Part B only conditional) | EXPERIMENTAL | Single dose of tolebrutinib (SAR442168) will be administered on Day 1 under fed condition |
| Part 1a | EXPERIMENTAL | 3 single ascending doses of SAR442168 or placebo in fasted and fed (high-fat breakfast) conditions |
| Part 1b | EXPERIMENTAL | 2 single doses of SAR442168 under fed conditions (moderate-fat breakfast). |
| Part 1c | EXPERIMENTAL | 1 single dose of SAR442168 under fasting and fed conditions (high-fat breakfast). |
| Part 1d | EXPERIMENTAL | 1 single dose of SAR442168 under fasting and fed conditions (Standardized high-fat breakfast). |
| Part 2 | EXPERIMENTAL | 3 ascending once-daily repeated single doses of SAR442168 or placebo for 14 days under fed conditions (moderate-fat breakfast) |
| Cohort 1 | EXPERIMENTAL | SAR442168 administered alone and together with gemfibrozil. 1 day washout for each administration of SAR442168. |
| Cohort 2 | EXPERIMENTAL | SAR442168 administered alone and together with rifampicin. 1 day washout for each administration of SAR442168. |
| Name | Type | Description |
|---|---|---|
| Tolebrutinib | DRUG | Pharmaceutical form:Tablet-Route of administration:oral |
| Placebo | DRUG | Pharmaceutical form:Tablet-Route of administration:oral |
| Teriflunomide | DRUG | Pharmaceutical form:Tablet-Route of administration:oral |
| Placebo to match Tolebrutinib | DRUG | Pharmaceutical form: Film-coated tablet Route of administration: Oral |
| Placebo to match Teriflunomide | DRUG | Pharmaceutical form: Tablet Route of administration: Oral |
| Teriflunomide HMR1726 | DRUG | Pharmaceutical form: Tablet Route of administration: Oral |
| gemfibrozil | DRUG | Tablet, taken orally |
| rifampicin | DRUG | Tablet, taken orally |
Inclusion Criteria: \- Participants with RMS, PPMS, or NRSPMS who completed the Phase 2b LTS (LTS16004) or 1 of the 4 Phase 3 pivotal tolebrutinib trials (EFC16033, EFC16034, EFC16645, EFC16035) on IMP. OR \- The Phase 2b LTS (LTS16004) or Phase 3 tolebrutinib pivotal trial participants who tempo...
Tolebrutinib is an investigational small molecule being developed for multiple sclerosis (MS), including relapsing MS, primary progressive MS, and non-relapsing secondary progressive MS. It is also studied in renal impairment and hepatic function abnormal conditions. Tolebrutinib is not FDA approved and remains in clinical development.
Tolebrutinib is a kinase inhibitor, belonging to the -tinib class of drugs. It targets Bruton's tyrosine kinase (BTK), a key enzyme in B-cell and microglia signaling pathways implicated in multiple sclerosis pathology. By inhibiting BTK, Tolebrutinib aims to modulate immune responses involved in MS.
Tolebrutinib is developed by Sanofi, a global biopharmaceutical company traded on the stock exchange under the ticker SNY. Sanofi is conducting clinical trials to evaluate the safety and efficacy of Tolebrutinib in multiple sclerosis and related conditions.
Tolebrutinib is in Phase 3 clinical development for multiple sclerosis. It has received FDA Breakthrough Therapy designation and Priority Review designation. However, Tolebrutinib is still investigational and not yet approved by the FDA for any indication.
Tolebrutinib has been studied in four clinical trials, including NCT03996291 (Phase 2, relapsing MS, completed), NCT06064539 (Phase 1, drug interaction, completed), NCT06106074 (Phase 1, tolerability and pharmacokinetics, completed), and NCT06372145 (Phase 3, long-term safety, active not recruiting). These trials have enrolled approximately 4,498 participants.
Yes, Tolebrutinib is also known as SAR442168. Clinical trial records frequently refer to the drug as SAR442168, such as in the Phase 2 study NCT03996291 and Phase 1 studies NCT06064539 and NCT06106074. Both names refer to the same investigational compound.