Eligibility Criteria for Exceptional Access Program Funding for Eculizumab

A patient must meet all 3 of the following criteria to obtain funding for initial treatment with eculizumab:

1. Confirmed diagnosis of aHUS at initial presentation, defined by:
   
   • Presence of an unexplained non-disseminated intravascular coagulation thrombotic microangiopathy (TMA)

   AND

   • Baseline ADAMTS-13 activity ≥10% on blood samples taken prior to plasma exchange or plasma infusion (PE/PI) 

   Note: If the sample for ADAMTS-13 was not collected prior to PE or PI, platelet counts >30 x 10⁹/L and eGFR <50 mL/min/1.73m² at TMA presentation will be accepted as predictive of ADAMTS-13 ≥10% in TMA patients. In this case, measurement of ADAMTS-13 can be taken 1-2 weeks following the last PE. The ADAMTS-13 result must be provided within 30 days of commencement of eculizumab and at least 1 week after the last PE. A 1-month interim funding for eculizumab will be provided. 

   AND

   • STEC-negative test in patients with a history of bloody diarrhea in the preceding 2 weeks

   AND

   • Other diagnoses and causes of TMA must be ruled out, as per preamble
2. Evidence of ongoing active and progressing TMA as defined by:
   
   • Thrombocytopenia (platelet count <150 x 10⁹/L) that is not explained by some other cause including secondary TMA; AND hemolysis as indicated by the documentation of 2 of the following: red blood cell (RBC) fragmentation (schistocytes) on the blood film; low or absent haptoglobin; or lactate dehydrogenase (LDH) above normal

   OR

   • Tissue biopsy confirming TMA in patients who do not have evidence of platelet consumption and hemolysis

   Note: Review by external clinical expert may be required to assess requests for patients with ongoing TMA that may not clearly meet the above criteria.

3. Evidence of at least 1 of the following documented clinical features of active organ damage or impairment:
   
   • Kidney impairment as demonstrated by one of the following:
     • A decline in estimated glomerular filtration rate (eGFR) or a rise in serum creatinine (SrCr) of >20% in a patient with pre-existing renal impairment; OR
     • SrCr > upper limit of normal (ULN) for age or eGFR <60 mL/min in patients who have no history of pre-existing renal impairment (i.e., who have no baseline eGFR measurement); OR
     • SrCr > the age-appropriate ULN in pediatric patients (subject to advice from a pediatric nephrologist); OR
     • Renal biopsy

   OR

   • Onset of neurological impairment related to TMA (e.g., visual field defect, hemiparesis, sensory loss, asymmetric limb weakness, confusion, loss of consciousness/coma, new onset seizure).

Note: Patients who have extra-renal complications related to TMA (e.g., TMA-related cardiac impairment, TMA-related gastrointestinal impairment, or TMA-related pulmonary impairment) will be reviewed by an external clinical expert.

Approval duration: 6 months