Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GDC-0853
Fenebrutinib · 10 trials · 6 indications
Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Weeks 4, 8, and 12. All MRI scans were read by a centralized reading center for efficacy endpoints. The total number of new Gd-enhancing T1 lesions were calculated as the sum of the individual number of new lesions observed at Weeks 4, 8 and 12. The lesion rate (new lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.
The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. The maximum UAS7 value is 42. A higher score indicates worse disease. A negative change score (Day 57 score minus Baseline score) indicates improvement.
The Systemic Lupus Erythematosus Responder Index (SRI)-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
An Adverse Event (AE) was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
An Adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE was any experience that suggested a significant hazard, contraindication, side effect or precaution that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
| Arm | Type | Description |
|---|---|---|
| Fenebrutinib | EXPERIMENTAL | Participants will receive oral (PO) fenebrutinib, with teriflunomide-matching placebo. |
| Teriflunomide | ACTIVE_COMPARATOR | Participants will receive PO teriflunomide, with fenebrutinib-matching placebo in a blinded fashion. |
| Ocrelizumab | ACTIVE_COMPARATOR | Participants will receive IV ocrelizumab and oral fenebrutinib-matching placebo. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive oral placebo. |
| Cohort 1: Placebo | PLACEBO_COMPARATOR | Participants received matching placebo twice daily from Day 1 to 56. |
| Cohort 1: GDC-0853 200mg BID | EXPERIMENTAL | Participants received GDC-0853 200mg twice daily from Day 1 to 56. |
| Cohort 2: Placebo | PLACEBO_COMPARATOR | Participants received matching placebo up to twice daily from Day 1 to 56. |
| Cohort 2: GDC-0853 50mg QD | EXPERIMENTAL | Participants received GDC-0853 50mg once daily from Day 1 to 56. |
| Cohort 2: GDC-0853 150mg QD | EXPERIMENTAL | Participants received GDC-0853 150mg once daily from Day 1 to 56. |
| Cohort 2: GDC-0853 200mg BID | EXPERIMENTAL | Participants received GDC-0853 200mg twice daily from Day 1 to 56. |
| GDC-0853 (150mg) QD | EXPERIMENTAL | Participants received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. |
| GDC-0853 (200mg) BID | EXPERIMENTAL | Participants received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. |
| GDC-0853 (200mg BID) Cohort 1 | EXPERIMENTAL | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. |
| GDC-0853 (200mg BID) Cohort 2 | EXPERIMENTAL | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | EXPERIMENTAL | Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | EXPERIMENTAL | Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | EXPERIMENTAL | Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 1: GDC-0853 Placebo + Adalimumab | ACTIVE_COMPARATOR | Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | PLACEBO_COMPARATOR | Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 2: GDC-0853 High Dose | EXPERIMENTAL | Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Cohort 2: GDC-0853 Placebo | PLACEBO_COMPARATOR | Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| Dose-escalation | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Fenebrutinib | DRUG | Participants will receive fenebrutinib. |
| Teriflunomide | DRUG | Participants will receive teriflunomide. |
| Placebo | DRUG | Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo. |
| Ocrelizumab | DRUG | Participants will receive ocrelizumab. |
| Placebo matched to ocrelizumab | DRUG | Participants will receive ocrelizumab-matching placebo. |
| Placebo matched to fenebrutinib | DRUG | Participants will receive fenebrutinib-matching placebo |
| GDC-0853 | DRUG | GDC-0853 will be administered orally at dosages of 50, 150 and 200mg to participants, as per the dosing schedules described above. |
| Adalimumab | DRUG | Participants will receive adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. |
| Folic Acid | DRUG | Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
| MTX | DRUG | Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines). |
Inclusion Criteria: * Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening * A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria * Ability to complete the 9-hole Peg Test (9-HPT) for each hand in \< 240 seconds * Ability to perform the Timed 25-foot Walk Test (...
Fenebrutinib is an investigational small molecule being studied for the treatment of multiple sclerosis, including relapsing multiple sclerosis and primary progressive multiple sclerosis. It is in Phase 3 clinical development and has not been approved for any indication. All four of its current trials enroll patients with relapsing forms of multiple sclerosis.
Fenebrutinib targets Bruton's tyrosine kinase, or BTK, and acts as a BTK inhibitor. BTK is an enzyme involved in the activation of B cells and myeloid cells, cell types implicated in the inflammatory processes of multiple sclerosis. Inhibiting BTK is the mechanism under investigation for reducing MS disease activity.
Fenebrutinib is developed by Roche Holding AG, which trades on the OTC market under the ticker RHHBY. Roche is running the clinical development program, which includes Phase 2 and Phase 3 studies in relapsing multiple sclerosis across North America, Europe, Latin America, Asia, and Africa.
Fenebrutinib is in Phase 3 clinical development. Two Phase 3 trials, NCT04586023 and NCT04586010, compare fenebrutinib with teriflunomide in relapsing multiple sclerosis. It is investigational and has not been approved by the FDA or any other regulatory agency for multiple sclerosis or any other condition.
Fenebrutinib is being studied in four active trials. NCT04586023 and NCT04586010 are Phase 3 studies versus teriflunomide in relapsing multiple sclerosis, with 751 and 746 participants. NCT05119569 is a Phase 2 efficacy study in relapsing MS, and NCT07161258 is a Phase 2 pharmacokinetic, safety, and tolerability study in children and adolescents with relapsing MS.
The fenebrutinib clinical program has a combined planned enrollment of 1,618 participants across four trials. The two Phase 3 studies in relapsing multiple sclerosis account for 1,497 of those participants, and all four trials are randomized, double-blind, and actively controlled.