Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as VAY736 PFS, VAY736 AI, VAY736, Ianalumab (VAY736), ianalumab s.c. q4w, ianalumab s.c. q12w
Ianalumab · 24 trials · 16 indications
The Sjögren's Syndrome Symptom Diary (SSSD) oral dryness score is a patient-reported measure assessing severity of mouth dryness. The mouth dryness symptom is scored daily on a numerical scale (higher scores = worse symptoms).
Cohort 1: To estimate the time to renal flare, increase in immunosuppressive medication, or death following study treatment withdrawal in participants who completed the SIRIUS-LN core study on double-blind treatment and achieved CRR or PRR at Week 140 of the core study
Number of participants with AEs and SAEs, including changes in vital signs and clinical laboratory measurements qualifying and reported as AEs.
Assessment of long-term safety and tolerability of ianalumab
Assessment of safety and tolerability of ianalumab (VAY736) in patients with active Sjogrens syndrome
SRI-4 response is defined as: * Systemic Lupus Erythematosus Disease Activity Index - 2000 (SLEDAI-2K) reduction from baseline of ≥ 4 points * No British Isles Lupus Assessment Group-2004 (BILAG-2004) worsening, defined as ≥ 1 new A or ≥ 2 new B items compared to baseline * No worsening in Physician Global Assessment of Disease Activity (PhGA), defined as an increase of ≥ 0.3 from baseline on a 0 to 3 visual analog scale
SRI-4 response is defined as: * Systemic Lupus Erythematosus Disease Activity Index - 2000 (SLEDAI-2K) reduction from baseline of ≥ 4 points * No British Isles Lupus Assessment Group-2004 (BILAG-2004) worsening, defined as ≥ 1 new A or ≥ 2 new B items compared to baseline * No worsening in Physician Global Assessment of Disease Activity (PhGA), defined as an increase of ≥ 0.3 from baseline on a 0 to 3 visual analog scale
A participant will be considered in SROT-12 if at least 75% of the platelet counts collected between visits Week 53 Day 1 and Week 65 Day 1 (Study Days 352 and 463) qualify as Response. Response is any platelet counts of at least 50 G/L in the absence of rescue treatment or new immune thrombocytopenia (ITP) treatment).
Time from randomization until treatment failure is defined as the time from randomization date until the first of the following events indicative of treatment failure: * platelet count below 30 G/L * start of a new ITP treatment * need for a rescue treatment * ineligibility to taper or inability to discontinue eltrombopag * death
Durable response: hemoglobin level ≥10 g/dL and ≥2 g/dL increase from baseline, for a period of at least eight consecutive weeks between W9 and W25, in the absence of rescue medication or prohibited treatment
* Plan A - United States of America and US reference countries * Plan B - EU, China, other non-US Regions and EU reference countries Dose response measured by change multi-dimensional disease activity as assessed by the physician. Score range is 0-123. Higher scores on the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states A negative change from baseline indicates improvement in disease status.
Efficacy (Plan A: US and US reference countries and Plan B: EU, China, other non-US Regions and EU reference countries) Dose response measured by change multi-dimensional disease activity as assessed by the physician. Score range is 0-123. Higher scores on the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states A negative change from baseline indicates improvement in disease status.
The primary objective is to demonstrate superiority of ianalumab compared to placebo, in achieving stable CRR (defined as estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73 m2 or no less than 85% of baseline, AND, 24-hour UPCR \<0.5 g/g) at Week 72 in active lupus nephritis (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous) participants on background SoC therapy.
TTF is defined as the time from start of treatment until any of a list of specific events is met.
The proportion of participants who tolerate ianalumab (9 mg/kg) is defined as those who do not experience any of the following events during the combination treatment period (up to Week 16): * Discontinuation due to an adverse event (AE) unrelated to efficacy * Adverse events leading to dose reduction or dose rate reduction * Adverse events resulting in study drug interruption.
To demonstrate the superiority of ianalumab, compared to placebo, in achieving 3/5 Revised Composite Response Index in Systemic Sclerosis 25 (rCRISS25) response at Week 52
To demonstrate the pharmacokinetics (PK) comparability of ianalumab 300 mg s.c. at steady state between the 1 x 2 mL AI and 2 x 1 mL PFS
To demonstrate the pharmacokinetics (PK) comparability of ianalumab 300 mg s.c. at steady state between the 1 x 2 mL AI and 2 x 1 mL PFS
To demonstrate the pharmacokinetics (PK) comparability of ianalumab 300 mg s.c. at steady state between the 1 x 2 mL PFS and 2 x 1 mL PFS.
To demonstrate the pharmacokinetics (PK) comparability of ianalumab 300 mg s.c. at steady state between the 1 x 2 mL PFS and 2 x 1 mL PFS.
Confirmed response is defined as a platelet count of equal or above 50 G/L at two (or more) consecutive assessments at least 7 days apart, in the absence of: * Rescue treatment for ≥4 weeks prior to the assessment of the platelet count, and * New immune thrombocytopenia (ITP) treatment before reaching a confirmed response.
Change from baseline in logarithm of salivary gland B/B+T cell ratio at Week 25 (EOT)
The primary endpoint was a composite of SRI-4 response at Week 29 with sustained reduction in oral corticosteroid from Week 17 through Week 29. Patients taking other rescue medication or prohibited medication or drop out before Week 29 were considered non-responders. SRI-4 response is defined as below: * having \>= 4 points reduction from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score (score is 0 to 105; a higher score indicating more severe disease) AND * no new British Isles Lupus Activity Group (BILAG)-2004 A organ domain score and no more than one new BILAG-2004 B organ domain scores compared with baseline AND * \<10 mm point increase from baseline with scale 0 to 100 mm in the physician's global assessment from baseline Sustained reduction in oral corticosteroid is defined as below: * =\< 5 mg/day or less than or equal to baseline dose, whichever was lower at Week 17 AND * no increase of that dose from Week 17 through Week 29
Difference in ALT normalization
The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score ranging 0-123. Higher scores on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states. A negative change from baseline indicates improvement in disease status.
The effect of VAY736 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12. The instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score (range 0-123). A reduction from baseline indicates improvement in patients.
Number of subjects with Adverse Events during the double blind treatment period.
The number of patients with adverse events after repeated subcutaneous (s.c) injections of a fixed dose of ianalumab
The area under the serum ianalumab concentration-time curve from time zero to the end of the dosing interval (AUCtau)
Observed maximum serum concentration of ianalumab following drug administration (Cmax)
Part 1 The number of patients with adverse events after single intravenous (i.v.) dose of VAY736. Patients are assessed weekly up to 34 weeks post dose or until B cells reach the recovery criteria Part 2 The number of patients with adverse events after single subcutaneous (s.c.) dose of VAY736. Patients are assessed weekly, bi-weekly, then every 4, 8 and 12 weeks up to 188 weeks post dose or until B cells reach the recovery criteria. Part 3 The number of patients with adverse events after repeated subcutaneous (s.c) injections of a fixed dose of VAY736. Patients are assessed bi-weekly, then every 4 weeks and 8 weeks up to 27 weeks from the first dose.
Part 2 The ratio of area under curve (AUC) for single s.c dose and intravenous dose is determined
In Part 3: After the first and last s.c. doses, the area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUCtau) will be determined
In Part 3: After the first and last s.c. doses, the Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) will be determined.
In Part 3: After the first and last s.c. doses, the Observed maximum plasma concentration following drug administration (Cmax) will be determined
In Part 3: After the first and last s.c. doses, the time to reach the maximum concentration after drug administration (Tmax) will be determined
In Part 3: After the first and last s.c. doses, the terminal elimination half-life (T1/2) will be determined
In Part 3: After the first and last s.c. doses, Area under the plasma concentration-time curve from time zero to infinity (AUCinf) will be determined.
In Part 3: After the first and last s.c. doses, the concentration of VAY736 during the treatment period, before each dose (Ctrough) will be determined
Part 1 The percentage of patients with adverse events after single intravenous (i.v.) dose of VAY736. Patients are assessed weekly up to 34 weeks post dose or until B cells reach recovery criteria. Part 2 The percentage of patients with adverse events after single subcutaneous (s.c.) dose of VAY736. Patients are assessed weekly, bi-weekly, then every 4, 8 and 12 weeks up to 68 weeks post dose or until B cells reach recovery criteria.. Part 3 The percentage of patients with adverse events after repeated subcutaneous (s.c) injections of a fixed dose of VAY736. Patients are assessed bi-weekly, then every 4 weeks and 8 weeks up to 27 weeks from the first dose.
| Arm | Type | Description |
|---|---|---|
| VAY736 - 300 mg | EXPERIMENTAL | VAY736 once monthly solution for injection for subcutaneous use. |
| Placebo | PLACEBO_COMPARATOR | Placebo once monthly solution for injection for subcutaneous use. |
| Study Treatment Withdrawal (cohort 1) | NO_INTERVENTION | (Cohort 1): Study Treatment-Withdrawal group. Participants who received blinded study treatment in the core study and achieve CRR or PRR at Week 140 in the core study will enter the extension study and discontinue study treatment while maintaining standard of care (SoC) medication, as required. If renal flare criteria are met, participants will be eligible to receive open-label ianalumab. |
| Open-Label Ianalumab (cohort 2) | EXPERIMENTAL | (Cohort 2): Open-Label Ianalumab group: Participants who received blinded study treatment throughout the core study and did not achieve CRR or PRR at Week 140 of the core study, or who had switched to open-label ianalumab during the core study, will be eligible or will continue to receive open-label ianalumab in the extension study. |
| Ianalumab monthly | EXPERIMENTAL | Ianalumab s.c. monthly |
| Ianalumab quarterly | EXPERIMENTAL | Ianalumab s.c. quarterly |
| Placebo monthly | PLACEBO_COMPARATOR | Placebo s.c. monthly |
| Ianalumab 3 Monthly | EXPERIMENTAL | Ianalumab 300 mg s.c. every three months and placebo once monthly between doses during initial double-blind treatment period. Open-label treatment and receive ianalumab 300 mg monthly. |
| ianalumab s.c. monthly | EXPERIMENTAL | ianalumab s.c. monthly |
| placebo s.c. monthly | PLACEBO_COMPARATOR | placebo s.c. monthly |
| Ianalumab s.c. quarterly | EXPERIMENTAL | Ianalumab s.c. quarterly |
| Ianalumab Lower dose | EXPERIMENTAL | Lower dose of ianalumab administered intravenously with corticosteroids oral or parental (if clinically justified) |
| Ianalumab Higher dose | EXPERIMENTAL | Higher dose of ianalumab administered intravenously with corticosteroids oral or parental (if clinically justified) |
| Treatment arm 1 - Lower dose | EXPERIMENTAL | Participants will receive eltrombopag and ianalumab lower dose |
| Treatment arm 2 - Higher dose | EXPERIMENTAL | Participants will receive eltrombopag and ianalumab higher dose |
| Treatment arm 3 - Placebo | PLACEBO_COMPARATOR | Participants will receive eltrombopag and placebo |
| Ianalumab low dose | EXPERIMENTAL | Participants will receive low dose ianalumab intravenously |
| Ianalumab high dose | EXPERIMENTAL | Participants will receive high dose ianalumab intravenously |
| Arm A | EXPERIMENTAL | ianalumab exposure level 1 |
| Arm B | EXPERIMENTAL | ianalumab exposure level 2 |
| Arm C | PLACEBO_COMPARATOR | placebo |
| Arm 1 - ianalumab s.c. q4w | EXPERIMENTAL | ianalumab s.c. q4w in addition to standard of care (SoC) |
| Arm 2 - ianalumab s.c. q12w | EXPERIMENTAL | ianalumab s.c. q12w in addition to SoC |
| Arm 3 - placebo s.c. q4w | PLACEBO_COMPARATOR | Placebo s.c. q4w in addition to SoC |
| Ianalumab + eltrombopag | EXPERIMENTAL | Participants will receive ianalumab in addition to eltrombopag. |
| Main cohort: Primary immune thrombocytopenia (ITP) | EXPERIMENTAL | All participants will be assigned to ianalumab 9 mg/kg plus investigator's choice thrombopoietin receptor agonist (IC TPO-RA). |
| Exploratory cohort: Primary Evans syndrome (ES) | EXPERIMENTAL | All participants will be assigned to ianalumab 9 mg/kg plus investigator's choice thrombopoietin receptor agonist (IC TPO-RA). |
| VAY736 (Ianalumab) | EXPERIMENTAL | Treatment Period 1: Ianalumab subcutaneous (s.c.) injection as defined in the protocol Treatment Period 2: Open-label (OL) Ianalumab subcutaneous (s.c.) injection as defined in the protocol |
| Cohort 1: Sequence 1 + Thigh | EXPERIMENTAL | Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) AI in TP2 in Thigh (1 x 2 mL) AI in ETP in Thigh/ Abdomen |
| Cohort 1: Sequence 1 + Abdomen | EXPERIMENTAL | Patients randomized to receive injection 1. X 2 mL) AI in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen |
| Cohort 1: Sequence 2 + Thigh | EXPERIMENTAL | Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh (1 X 2 mL) AI in TP2 in Thigh (1 x 2 mL) AI in ETP in Thigh/ Abdomen |
| Cohort 1: Sequence 2 + Abdomen | EXPERIMENTAL | Patients randomized to receive injection 1. X 2 mL) AI in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (1 x 2 mL) AI in ETP in Thigh/ Abdomen |
| Cohort 2: Sequence 1 + Thigh | EXPERIMENTAL | Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Thigh 1. X 2 mL) PFS in TP2 in Thigh 2. x 1 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm |
| Cohort 2: Sequence 1 + Abdomen | EXPERIMENTAL | Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Abdomen 2. x 1 mL) PFS in TP2 in Abdomen (2 x 1 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm |
| Cohort 2: Sequence 1 + Upper Arm | EXPERIMENTAL | Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Upper Arm 1. X 2 mL) PFS in TP2 in Upper Arm 2. x 1 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm |
| Cohort 2: Sequence 2 + Thigh | EXPERIMENTAL | Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Thigh 2. x 1 mL) PFS in TP2 in Thigh (2 x 1 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm |
| Cohort 2: Sequence 2 + Abdomen | EXPERIMENTAL | Patients randomized to receive injection (2 x 1 mL) PFS in TP1 in Abdomen 1. X 2 mL) PFS in TP2 in Abdomen 2. x 1 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm |
| Cohort 2: Sequence 2 + Upper Arm | EXPERIMENTAL | Patients randomized to receive injection 1. X 2 mL) PFS in TP1 in Upper Arm 2. x 1 mL) PFS in TP2 in Upper Arm (2 x 1 mL) PFS in ETP in Thigh/ Abdomen/ Upper Arm |
| Single-arm | EXPERIMENTAL | All eligible participants will receive ianalumab at the same dose. |
| Treatment Arm | EXPERIMENTAL | Ianalumab 300 mg subcutaneous monthly |
| Cohort 1 VAY736 | EXPERIMENTAL | Blinded treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49. |
| Cohort 1 VAY736 Placebo | PLACEBO_COMPARATOR | Blinded treatment phase: VAY736 matching placebo administered subcutaneously (s.c.) every 4 weeks as multiple doses of placebo 0 mg until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label treatment phase: VAY736 administered subcutaneously (s.c.) every 4 weeks as multiple doses of VAY736 150 mg (total dose being VAY736 300 mg) until Week 49. |
| Cohort 2 CFZ533 | EXPERIMENTAL | Blinded treatment phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49. |
| Cohort 2 CFZ533 Placebo | PLACEBO_COMPARATOR | Blinded treatment phase: CFZ533 matching placebo administered intravenously (i.v) every 4 weeks as multiple doses of placebo 0 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 25 + Standard of Care (SoC) for systemic lupus erythematosus (SLE). Open-label phase: CFZ533 administered intravenously (i.v) every 4 weeks as multiple doses of CFZ533 150 mg, based on body weight (BW) of the patients (10 mg/kg (\>= 50 kg BW) and 13 mg/kg (\< 50 kg BW)) until Week 49. |
| Arm 1 | EXPERIMENTAL | VAY736 Dose 1 |
| Arm 2 | EXPERIMENTAL | VAY736 Dose 2 |
| Arm 3 | EXPERIMENTAL | VAY736 Dose 3 |
| Arm 4 | PLACEBO_COMPARATOR | Placebo |
| VAY736 dose 1 - 5mg | EXPERIMENTAL | VAY736 low |
| VAY736 dose 2 - 50mg | EXPERIMENTAL | VAY736 medium |
| VAY736 dose 3 - 300 mg | EXPERIMENTAL | VAY736 high |
| VAY736 3 mg/kg | EXPERIMENTAL | single dose iv of VAY736 at a dose of 3mg/kg |
| VAY736 10 mg/kg | EXPERIMENTAL | single dose iv of VAY736 at a dose of 10mg/kg |
| Reference VAY736 Drug Product | ACTIVE_COMPARATOR | Powder for solution for injection / infusion |
| Test VAY736 Drug Product | EXPERIMENTAL | Solution for injection |
| VAY736 | EXPERIMENTAL | VAY736 active |
| Name | Type | Description |
|---|---|---|
| VAY736 | DRUG | VAY736 once monthly solution for injection for subcutaneous use. |
| Placebo | DRUG | Placebo once monthly solution for injection for subcutaneous use. |
| Ianalumab | DRUG | Ianalumab (VAY736) is a human monoclonal antibody (mAb) of the IgG1/κ-class, directed against B cells and binding to BAFF receptor (BAFF-R). |
| Ianalumab (VAY736) | DRUG | Ianalumab 300 mg / 2 mL, PFS or AI, monthly or every 3 months, solution for injection for subcutaneous use |
| Corticosteroids | DRUG | Oral or parental (if clinically justified) |
| Eltrombopag | DRUG | Film-coated tablet for oral use |
| ianalumab s.c. q4w | DRUG | ianalumab s.c. q4w in addition to SoC |
| ianalumab s.c. q12w | DRUG | ianalumab s.c. q12w in addition to SoC |
| placebo s.c. | DRUG | placebo s.c. q4w in addition to SoC |
| thrombopoietin receptor agonist (TPO-RA) | DRUG | IC TPO-RAs will be administered according to the respective United States Prescribing Information (USPIs) |
| VAY736 1ml PFS | BIOLOGICAL | Solution for injection. |
| VAY736 2 ml PFS | BIOLOGICAL | Solution for injection |
| VAY736 2ml AI | BIOLOGICAL | Solution for injection. |
| VAY736 Placebo | DRUG | solution for injection; 0 mg/mL administered as 2 mL s.c. injection |
| CFZ533 | DRUG | 150 mg/mL as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion |
| CFZ533 Placebo | DRUG | Placebo as concentrate in vial for infusion, administered at a dose of 10 mg/kg as i.v. infusion |
Inclusion Criteria: * Male or female participants ≥ 18 years of age or as per country-specific legal adult age, whichever is higher * Classification of Sjögren's disease according to ACR/EULAR 2016 criteria. * Seropositive for anti-Ro/SSA antibodies at screening * SSSD oral dryness score ≥ 5 and ov...
Top 18 of 19 competitors
Ianalumab is an investigational monoclonal antibody developed by Novartis AG for immunology indications. It is being studied in autoimmune hepatitis, diffuse cutaneous systemic sclerosis, lupus nephritis, primary immune thrombocytopenia, rheumatoid arthritis, and Sjögren's syndrome. It is administered subcutaneously, with dosing schedules including every four weeks and every twelve weeks.
Ianalumab targets TNFRSF13C, also known as the BAFF receptor, and acts as a binding agent. By engaging this receptor, the antibody is designed to act on B cell pathways relevant to autoimmune disease. Its clinical program spans several B cell mediated conditions, including lupus nephritis, Sjögren's syndrome, and primary immune thrombocytopenia.
Ianalumab is developed by Novartis AG, which trades under the ticker NVS. Novartis is running the clinical program across multiple autoimmune indications, including Phase 3 studies in Sjögren's disease and lupus nephritis and Phase 2 studies in primary immune thrombocytopenia.
Ianalumab is in Phase 2 and Phase 3 clinical development and is not approved for any indication. Phase 3 studies include a Sjögren's disease trial and a lupus nephritis extension study, while Phase 2 programs cover primary immune thrombocytopenia, including a pediatric study and a combination study with a thrombopoietin receptor agonist.
Ianalumab trials include NCT07621809, a Phase 3 study in Sjögren's disease with high symptom burden, and NCT06711887, the Phase 3 SIRIUS-LN extension study in lupus nephritis. Phase 2 studies include NCT07421167 in primary immune thrombocytopenia and Evans syndrome and NCT07660172 in pediatric primary immune thrombocytopenia. Across its program, ianalumab trials have enrolled about 1,631 participants.
Yes, ianalumab is the same drug as VAY736. VAY736 appears in trial titles and in subcutaneous dosing descriptions such as VAY736 1ml PFS, VAY736 2ml AI, and ianalumab s.c. q4w or q12w. Readers searching for VAY736 are looking at the same Novartis monoclonal antibody program.