A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)

Participants were considered to be on dialysis at baseline or at Week 25 if dialysis occurred within 5 days prior to the first crovalimab administration or prior to the end date of the primary treatment period, respectively. The percentage of participants who required dialysis at baseline and Week 25 has been reported here. Percentages have been rounded off.

Participants were considered as being on dialysis at baseline or at Week 25 if dialysis occurred within 5 days prior to the first crovalimab administration or prior to the end date of the primary treatment period, respectively. Participants who were on dialysis at any time point from baseline to Week 25 were classified as "Initiated dialysis at any time point ". Participants who remained dialysis-free throughout the primary treatment period were classified as "Remained dialysis free throughout". Participants who were on dialysis at Week 25 were classified as "Remained on dialysis". Participants who discontinued dialysis at Week 25 were classified as "Discontinued dialysis. Percentages have been rounded off.

GFR is an index of kidney function that describes the flow rate of filtered fluid through the kidneys. It was categorized according to chronic kidney disease (CKD) staging criteria. eGFR was calculated using the creatinine-based bedside Schwartz equation for adolescents and 2009 CKD-Epidemiology Collaboration (EPI) creatinine equation for adults. Formula for creatinine-based bedside Schwartz equation was eGFR (milliliters per minute per 1.73 square meter [mL/min/1.73 m^2])=0.413*(height [ht]/serum creatinine [sCr]), if height is expressed in centimeters, or 41.3*(ht/sCr), if height is expressed in meters, and formula for 2009 CKD-EPI creatinine equation was eGFR (mL/min/1.73 m^2)= 141*min(sCr /κ,1)^α*max(sCr/κ,1)^ -1.209*0.993^AGE[*1.018 if female][*1.159 if black], κ was 0.7 for females and 0.9 for males, α was -0.329 for females and -0.411 for males, min indicated the minimum of sCr/κ or 1, and max indicated the maximum of sCr/κ or 1.

GFR is an index of kidney function that describes the flow rate of filtered fluid through the kidneys. It was categorized according to CKD staging criteria. eGFR was calculated using the creatinine-based bedside Schwartz equation for adolescents and 2009 CKD- EPI creatinine equation for adults. Formula for creatinine-based bedside Schwartz equation was eGFR (mL/min/1.73 m^2)=0.413*(ht/sCr), if height is expressed in centimeters, or 41.3*(ht/sCr), if height is expressed in meters, and formula for 2009 CKD-EPI creatinine equation was eGFR (mL/min/1.73 m^2)= 141*min(sCr /κ,1)^α*max(sCr/κ,1)^ -1.209*0.993^AGE[*1.018 if female][*1.159 if black], κ was 0.7 for females and 0.9 for males, α was -0.329 for females and -0.411 for males, min indicated the minimum of sCr/κ or 1, and max indicated the maximum of sCr/κ or 1.

CKD stage assessed using eGFR, classified per National Kidney Foundation CKD staging criteria: grade 1 (≥90 mL/min/1.73 m²; normal or high), grade 2 (60-89 mL/min/1.73 m²; mildly decreased), grade 3a (45-59 mL/min/1.73 m²; mildly to moderately decreased), grade 3b (30-44 mL/min/1.73 m²; moderately to severely decreased), grade 4 (15-29 mL/min/1.73 m²; severely decreased), grade 5 (<15 mL/min/1.73 m²; kidney failure). Change in CKD stage from baseline to Week 25, categorized as improved (participants who improved in CKD stage from baseline to Week 25 were based on number of participants who completed 24 weeks \& were not stage 1 at baseline), stable (no change), or worsened (CKD stage 1-4 at baseline) among participants who completed 24 weeks of treatment. Percentages rounded off.

Fatigue was measured by the FACIT-Fatigue questionnaire in adult participants only (≥18 years at baseline). It consists of 13 items that assess fatigue using a 7-day recall period. Items are scored on a 0= 'Not at all' to 4= 'Very much so' response scale. Relevant items are reverse scored, and all items are summed to create total score where higher scores are indicative of better functioning (i.e., less fatigue). The FACIT-Fatigue total score ranges from 0 to 52, with higher scores representing less fatigue; therefore, an increase in score represents an improvement in fatigue. Only categories with non-zero values were reported.

This event was confirmed at two separate assessments obtained at least 4 weeks (a minimum of 26 days) apart and any measurement in between. Percentages are rounded off.

Percentages are rounded off.

Percentages are rounded off.

cTMAr was defined by meeting all of the following criteria at two separate assessments, obtained at least 4 weeks (a minimum of 26 days) apart, and any measurement in between: Platelet count ≥ LLN; LDH ≤ ULN; and ≥ 25% decrease in serum creatinine from baseline and > ULN. Kaplan-Meier (K-M) method was used to estimate median time to cTMAr. Data for participants who did not reach cTMAr during the primary treatment period were censored at the date of their last visit when cTMAr was assessed during the primary treatment period or prior to the treatment discontinuation, whichever was earlier. Data for participants who received a prohibited therapy during the primary treatment period were censored at the date of the first received prohibited therapy during the primary treatment period or prior to the treatment discontinuation, whichever was earlier.

cTMAr was defined by meeting following criteria at 2 separate assessments, obtained at least 4 weeks (minimum of 26 days) apart \& any measurement in between: Platelet count ≥ LLN; LDH ≤ ULN; \& ≥25% decrease in serum creatinine from baseline \& > ULN. Duration of cTMAr was calculated as time from start of cTMAr to end of cTMAr. End of cTMAr was when all above-mentioned criteria were met during same visit \& confirmed at an assessment that took place at least 4 weeks (minimum of 26 days) later. K-M method was used to estimate median duration of cTMAr. Data for participants with no observed end of cTMAr at clinical cutoff date (CCOD) were censored at the date of their last visit when cTMAr was assessed before CCOD or before treatment discontinuation, whichever was earlier. Data for participants who received a prohibited therapy prior to the CCOD were censored at date of the first received prohibited therapy or prior to the treatment discontinuation, whichever was earlier.

cTMAr at Week 25 was defined by meeting all of the three cTMAr criteria at Week 25: Platelet count ≥ LLN; LDH ≤ ULN; and ≥ 25% decrease in serum creatinine from baseline and > ULN. Percentage has been rounded off.

mTMAc was considered not maintained if all of the following criteria were met during one of the visits between baseline and Week 25, and were confirmed at an assessment that took place at least 4 weeks (a minimum of 26 days) later: Platelet count < LLN; LDH > ULN; and 25% increase in serum creatinine from baseline and > ULN.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Infusion-related and injection-site reactions were adverse events that occured during or within 24 hours after crovalimab administration and were judged to be related to study drug infusion or injection.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

In this study, the risk of DTDC is relevant only to participants who might switch to crovalimab from eculizumab or ravulizumab treatment at study enrollment, and to participants who discontinued crovalimab and switch to eculizumab or ravulizumab. Type III hypersensitivity may occur due to the transient formation of DTDCs made of eculizumab or ravulizumab, crovalimab, and C5 in participants switching from eculizumab or ravulizumab to crovalimab.

Participants will be considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following study drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater than the titer of the baseline sample (treatment-enhanced ADA response).