eculizumab

The mean (95% Confidence Interval) of patient-level Adjudicated On-trial annualized relapse rate (ARR)

The mean change of Myasthenia Gravis Activities of Daily Living Profile (MG-ADL) total score from baseline at Week 26 along with 2-sided 95% CI

The criteria for complete TMA response were: 1. Normalization of platelet count (defined as platelet count ≥ 150000/microliter (ul). 2. Normalization of lactate dehydrogenase (LDH, defined as LDH ≤ upper limit of normal \[ULN\]). 3. ≥ 25% improvement in serum creatinine from baseline.

Blood samples were collected for measurement of serum LDH at specified timepoints. Statistical analysis was performed using a mixed model for repeated measures (MMRM), including the percentage change from baseline of LDH at the scheduled visits from Week 1 to Week 12 as the dependent variable, with the fixed categorical effect of visit, fixed continuous effect of LDH baseline value as covariates, and participant as random effect. Assessed at baseline, 1, 2, 3, 4, 6, 8, 10, and 12 weeks, Week 12 reported. A decrease indicated a reduction in disease activity.

The mobility of the participants was evaluated on a 7 point disability functional grade scale and described as Hughes FG score of 0 (Healthy, no signs or symptoms of Guillain-Barré syndrome); 1 (Minor signs or symptoms and able to run); 2 (Able to walk 5 metre (m) across an open space without assistance); 3 (Able to walk 5 m across an open space with the help of one person and waist-level walking-frame, stick, or sticks); 4 (Chairbound/bedbound: unable to walk as in 3); 5 (Requiring assisted ventilation \[for at least part of day or night\]) and 6 (Dead), where higher numbers indicate more severe impairment. The Kaplan-Meier estimate of time to event of FG\<=1 is reported. Time (days) to first event=Date of first event-Date of first dose+1. Participants who discontinued early without achieving FG \<= 1 were censored at the date of discontinuation. Participants who completed the study without achieving FG\<=1 were censored at the date of study completion.

The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher scores indicating more severe disease.

An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent adverse events (TEAEs) were defined as an AE with onset on or after the first study drug dose in Study ECU-NMO-302. A serious adverse event (SAE) was defined as an untoward medical occurrence that at any dose either results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

The C-SSRS is a validated questionnaire to capture occurrence, severity, and frequency of suicide-related thoughts and behaviours, and has a binary response (yes/no). Suicidal Ideation: a "yes" answer to any one of 5 suicidal ideation questions: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Planned) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; and Active Suicidal Ideation with Specific Plan and Intent. Suicidal Behaviour: a "yes" answer to any of 5 suicidal behaviour questions: Preparatory Acts or Behaviour, Aborted Attempt, Interrupted Attempt, Actual Attempt (non-fatal), and Completed Suicide. Suicidal Ideation or Behaviour: a "yes" answer to the following question: Self-injurious behaviour without suicidal intent.

An On-trial Relapse was defined as a new onset of neurologic symptoms or worsening of existing neurologic symptoms with an objective change (clinical sign) on neurologic examination that persisted for more than 24 hours as confirmed by the treating physician.

The On-trial ARR was computed as the total number of relapses divided by the total number of participant years in the study period.

Treatment-emergent adverse events (TEAEs) are adverse events with onset on or after the first study drug dose in Study ECU-MG-302. Likewise, treatment-emergent serious adverse events (TESAEs) are serious adverse events that onset on or after the first study drug dose in Study ECU-MG-302. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

In the Worst-Rank analysis, the 125 total patients were ranked from best outcome (rank/score of 1) to worst outcome (rank/score of 125).

Results are reported for the DGF composite endpoint, defined as the occurrence of DGF (dialysis for any reason in the first 7 days post transplantation), graft loss, death, or loss to follow-up (including discontinuation) in the first 7 days post transplantation and for each item of the composite endpoint. Loss to follow-up included withdrawal due to any reason other than death. The sum of the counts in the events that make up the DGF composite may be greater than the composite count, because a participant who experienced multiple events was only counted once in the composite.

Results are reported for post-transplantation treatment failure and composite endpoints, defined as the occurrence of biopsy-proven acute antibody-mediated rejection (AMR), graft loss, death, or loss to follow-up (including discontinuation) in the first 9 weeks post transplantation. The diagnosis of acute AMR (occurring within the first 9 weeks post transplantation) was based on kidney allograft dysfunction and a biopsy performed due to suspected rejection, proteinuria, increased serum creatinine, or acute tubular necrosis. Treatment failure was the occurrence of at least 1 of the composite endpoint components by Week 9 post transplantation. A participant experiencing multiple events was only counted once for the composite endpoint.

Analysis of primary endpoint will occur after all patients have reached 8 weeks of treatment. The response rate will be summarized as patients who are either a complete or partial responder.

Proportion of Patients with Complete TMA response was determined and defined by normalization of hematological parameters (platelet count and LDH) and ≥ 25% improvement in serum creatinine from baseline which was sustained for at least two consecutive measurements obtained at least four weeks apart).

Proportion of Patients with Complete TMA response was determined and defined by normalization of hematological parameters (platelet count and LDH) and preservation of renal function (defined as \< 25% increase in serum creatinine from baseline) which were sustained for at least two consecutive measurements obtained at least four weeks apart.

Proportion of Patients with Modified Complete TMA response through 26 weeks of treatment was determined and defined by normalization of hematological parameters (platelet count and LDH) and improvement in renal function (defined as ≥ 25% reduction from the baseline value in serum creatinine, which were sustained for at least two consecutive measurements obtained at least four weeks apart.

TMA Event-free status is defined as the absence for at least 12 weeks of \[1\] decrease in platelet count of \> 25% from the Platelet Count Pre-PT Baseline Set Point; \[2\] PT while the patient is receiving eculizumab, and \[3\] new dialysis.

Hematologic Normalization was defined as normalization of both platelet count and lactic dehydrogenase (LDH) sustained for at least two consecutive measurements which spanned a period of at least four weeks.

The primary objective of the study (per protocol) was to assess the effect of eculizumab to reduce TMA as measured by platelet count change from baseline (BL) during the Treatment Period (26 weeks) in patients with plasma therapy (PT)-resistant aHUS (protocol defined), including assessment of the proportion of patients who achieved Platelet Count Normalization from baseline through 26 weeks. Platelet Count Normalization was defined as the platelet count observed to be ≥150 x 10\^9/L on at least two consecutive measurements which span a period of at least four weeks.