Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication CABLIVI is indicated for the treatment of adult and pediatric patients 12 years of age and older with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy. FDA label
Also known as Caplacizumab Dose 1 iv (single-dose), Caplacizumab Dose 1, Caplacizumab (ALX-0081), Cablivi®, ALX-0081, anti-vWF Nanobody
Caplacizumab · 6 trials · 5 indications
Remission was defined as sustained clinical response with either no TPE and no anti- von Willebrand factor (vWF) therapy for \>=30 days (clinical remission) or with attainment of a disintegrin and metalloproteinase with a thrombospondin type 1 motif13 (ADAMTS13) activity level \>=50% (complete ADAMTS13 remission), whichever occurred first. Clinical response was defined as sustained platelet count \>=150 × 10\^9/liter (L) and lactate dehydrogenase (LDH) \<1.5 × upper limit of normal (ULN) and no clinical evidence of new or progressive ischemic organ injury for at least 2 consecutive visits.
aTTP-related events were defined as: aTTP-related death, recurrence of aTTP (defined as recurrent thrombocytopenia requiring initiation of daily PE) or at least one major thromboembolic event (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, or deep venous thrombosis). Percentage of participants with at least one aTTP-related events during the study were reported in this outcome measure.
aTTP-related events were defined as: aTTP-related death, recurrence of aTTP (defined as recurrent thrombocytopenia requiring initiation of daily PE) or at least one major thromboembolic event (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism or deep venous thrombosis).
Time to first aTTP-related events was defined as the duration of time (in days) from Baseline up to first aTTP-related event in LTS16371. Participants without an event during LTS16371 were censored at the end of the study. Kaplan-Meier method was used for the analysis.
Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.
Recurrence of aTTP was defined as recurrent thrombocytopenia requiring initiation of daily PE.
Time to first recurrence of disease (aTTP) was defined as the duration of time (in days) from Baseline up to first recurrence of aTTP event in LTS16371. Recurrence of aTTP: defined as recurrent thrombocytopenia requiring initiation of daily PE. Participants without an event during LTS16371 were censored at the end of the study. Kaplan-Meier method was used for the analysis.
Major thromboembolic events (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, or deep venous thrombosis) were assessed based on Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). Reported major thromboembolic events included TTP recurrences.
Major thromboembolic events (e.g., myocardial infarction, cerebrovascular accident, pulmonary embolism, or deep venous thrombosis) were assessed based on SMQ. Reported major thromboembolic events included TTP recurrences.
Time to first major thromboembolic event was defined as the duration of time (in days) from Baseline up to first major thromboembolic event in LTS16371. Participants without an event during LTS16371 were censored at the end of the study. Kaplan-Meier method was used for the analysis.
The RBANS is a 30-minute comprehensive screening test with five individual domains (immediate memory, delayed memory, attention, language, and visuospatial ability) to examine the cognitive mental status of a participant. Scores from all individual domain were aggregated into a total score and thus RBANS total score ranged from 40 to 160, where higher scores reflected better performance.
HIT-6 is an easy to administer assessment that was used as a clinical evaluation of the impact of headache on a participant's QoL in both clinical practice and clinical research. The questionnaire included 6 questions covering the 6 areas of functioning most impacted in headache sufferers including pain, role functioning (the ability to carry out usual activities), social functioning, vitality (energy/ fatigue), cognitive functioning, and psychological/emotional distress. Total HIT-6 scores (sum of all individual questions) ranged from 36 (best outcome) to 78 (worst outcome), where higher scores indicated worse condition.
The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Physical functioning domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in physical functioning domain score at months 12, 24, and 36 were reported in this outcome measure.
The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Role Functioning/Physical domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in role functioning/physical domain score at months 12, 24, and 36 were reported in this outcome measure.
The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Role functioning/emotional domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in role functioning/emotional domain score at months 12, 24, and 36 were reported in this outcome measure.
The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Energy/fatigue domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in energy/fatigue domain score at months 12, 24, and 36 were reported in this outcome measure.
The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Emotional well-being domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in emotional well-being domain score at months 12, 24, and 36 were reported in this outcome measure.
The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Social functioning domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in social functioning domain score at months 12, 24, and 36 were reported in this outcome measure.
The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Pain domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in pain domain score at months 12, 24, and 36 were reported in this outcome measure.
The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. General Health domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in general health domain score at months 12, 24, and 36 were reported in this outcome measure.
The SF-36 consisted of 36 items that was summarized into 8 domains: physical functioning, social functioning, role functioning/physical, role functioning/emotional, emotional well-being, energy/fatigue, pain, general health and an additional single item covering change in health status. Change in health status scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. Change from baseline in change in health status score at months 12, 24, and 36 were reported in this outcome measure.
Drug-induced TE ADA positive was based on the outcome of a tiered assay approach that included a modified ADA (mADA) method to eliminate the effects of pre-existing antibodies (pre-Ab). TE ADA responses reported here included both pre-Ab positive and negative responses. A participant was considered as drug-induced TE ADA positive if post-dose samples were positive, regardless of the status of pre-dose samples in the ADA and modified ADA assay.
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. 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 or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
Platelet count response was defined as initial platelet count ≥ 150,000/μL with subsequent stop of daily PE within 5 days. It refers to the first time both conditions, platelet count ≥ 150,000/μL and the stop of daily PE within 5 days, were met.
Proportion of participants with a recurrence of aTTP during the overall study period. The success criterion for this study is proportion of evaluable participants (per-protocol population) with a recurrence of aTTP during the overall study period to be 20% or less.
Time-to-response, defined by the achievement of platelet count response, confirmed at 48 hours after the initial reporting of this response. Platelet response was defined as recovery of platelets ≥ 150,000/µL. This response had to be confirmed at 48 hours after the initial reporting of platelet recovery ≥ 150,000/µL by a de novo measure of platelets ≥ 150,000/µL and lactate dehydrogenase (LDH) ≤ 2x upper limit of normal (ULN) (i.e., 'confirmed platelet response').
| Arm | Type | Description |
|---|---|---|
| Caplacizumab & immunosuppressive therapy without 1st-line TPE | EXPERIMENTAL | All participants will receive open label caplacizumab daily and immunosuppressive therapy (corticosteroid +/-anti-CD20 therapy antibody \[rituximab or biosimilar\]) without first line TPE |
| caplacizumab | EXPERIMENTAL | Participants who completed study ALX0681-C301 (NCT02553317) with standard of care (plasma exchange \[PE\], corticosteroid and other immunosuppressive agents) or caplacizumab with PE and immunosuppressive agents were enrolled in study LTS16371. Participants upon each recurrence of aTTP in LTS16371 and not meeting any criteria (namely: pregnancy, history of severe and/or serious hypersensitivity reaction to investigational medicinal product \[IMP\], withdrawal before receiving IMP, received more than 1 PE) were treated with caplacizumab initial 10 milligrams (mg) intravenous dose followed by a daily 10 mg subcutaneous injections during the period of PE and for 30 days after stop of PE (and eventually 28-day extension period, if needed). Participants with or without recurrence were followed up twice yearly up to maximum of 36 months in LTS16371. |
| Placebo | PLACEBO_COMPARATOR | Placebo once daily |
| ALX-0081 | EXPERIMENTAL | - |
| GPIIb/IIIa inhibitor | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Caplacizumab | DRUG | Lyophilized powder for solution for injection. |
| Corticosteroids | DRUG | Solution for injection or Tablet |
| anti-CD20 antibody | BIOLOGICAL | Solution for injection |
| Standard of Care | OTHER | • PE with plasma (e.g., fresh frozen plasma, solvent detergent/viral-inactivated plasma, cryosupernatant), • Corticosteroid treatment and • Use of other immunosuppressive agents (e.g., rituximab). |
| Placebo | BIOLOGICAL | * First day of treatment: i.v. injection prior to PE followed by a s.c. injection (in the abdominal region) after completion of PE on that day. * Subsequent days of treatment during PE: daily s.c. injection (in the abdominal region) following PE. * Treatment after PE period: daily s.c. injections for 30 days. If the underlying immunological disease was not resolved, treatment could be extended for a maximum of 4 additional 1-week periods (i.e., 28 days) and was to be accompanied by optimization of immunosuppression. |
| Caplacizumab (ALX-0081) | DRUG | Pharmaceutical form:Lyophilized powder for solution for injection Route of administration: IV (first dose), SC (all subsequent doses) |
| Plasma exchange (PE) | DRUG | Pharmaceutical form:Plasma (e.g. fresh frozen plasma) Route of administration: Plasma exchange |
| Corticosteroid treatment (Methylprednisolone or prednisolone) | DRUG | Pharmaceutical form:Solution for injection or Tablet Route of administration: IV or Oral |
| Immunosuppressive treatment (eg, rituximab) | DRUG | Pharmaceutical form:Solution for injection (depending on product) Route of administration: IV (depending on product) |
| ALX-0081 | DRUG | 4 i.v. bolus injections, once every 6 hours; first dose of 6 mg, three subsequent doses of 4 mg |
| ReoPro® | DRUG | 0.25 mg/kg i.v. bolus injection followed by continuous i.v. infusion of 0.125 µg/kg/min (to a max. of 10 µg/min) for 12 hours |
Inclusion Criteria: Participants with a clinical diagnosis of iTTP (initial or recurrent), which includes thrombocytopenia, microangiopathic hemolytic anemia (eg, presence of schistocytes in peripheral blood smear) and relatively preserved renal function. The iTTP diagnosis should be confirmed by A...
Caplacizumab is used for acquired thrombotic thrombocytopenic purpura, a rare blood disorder also called aTTP. It is a monoclonal antibody developed for this hematology indication and has been studied in adults with immune-mediated thrombotic thrombocytopenic purpura, including regimens given alongside immunosuppressive therapy.
Caplacizumab targets von Willebrand factor, abbreviated VWF. It acts as an inhibitor of VWF, a protein involved in platelet adhesion and clot formation. By binding VWF, the antibody is designed to interfere with the VWF-mediated platelet aggregation that drives the small blood clots characteristic of thrombotic thrombocytopenic purpura.
Caplacizumab is developed by Sanofi, which trades under the ticker SNY. Sanofi is the company behind the caplacizumab clinical program in acquired thrombotic thrombocytopenic purpura, and the drug is also known by the research designation ALX-0081.
Caplacizumab has been studied in Phase 3 clinical development for acquired thrombotic thrombocytopenic purpura. Its trial program includes completed Phase 3 studies as well as a completed Phase 2 trial in Japanese patients, and the overall program enrolled 324 participants across randomized, double-blind, placebo-controlled studies.
Completed caplacizumab trials include NCT02553317, a Phase 3 study in acquired thrombotic thrombocytopenic purpura with 145 patients, and NCT05468320, a Phase 3 study of caplacizumab with immunosuppressive therapy without first-line plasma exchange in 51 adults. Other completed studies are NCT02878603, the Post-HERCULES follow-up study with 104 patients, and NCT04074187, a Phase 2 trial in 21 Japanese patients.
Yes, caplacizumab is also known by the research name ALX-0081. Other names used for the same asset include Caplacizumab Dose 1 and Caplacizumab Dose 1 iv (single-dose). These refer to the same monoclonal antibody developed by Sanofi for acquired thrombotic thrombocytopenic purpura, so searches under any of these names point to the same drug.