Inclusion criteria

Written patient informed consent must be obtained prior to start of treatment, including
all necessary consents (or their legal representatives, where applicable).

1. 1. Male or female, 12 years of age (inclusive) or older on the day of informed consent
signature.

2. Confirmed diagnosis of sickle cell disease by hemoglobin electrophoresis or high
performance liquid chromatography (HPLC) [performed locally]. All sickle cell disease
genotypes are eligible (HbSS, HbSβ0, HbSC, HbSβ+, and others).

3. History of recurrent VOC as assessed by the Treating Physician.

4. Patients receiving HU/HC, L-glutamine (Endari), or other therapies as prevention
therapy and continue to experience VOC while on any of these treatments.

• Patients can continue taking the preventive therapy.

5. Patient is not a candidate to be treated with alternative treatment options or has
discontinued alternative treatments due to unacceptable benefit risk as documented by
the Treating Physician.

6. Patient must meet the following laboratory values prior to treatment:

- Absolute Neutrophil Count ≥1.0 x 10^9/L

- Platelets ≥ 75 x 10^9/L

- Hemoglobin (Hgb) ≥ 4.0 g/dL

- Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 using CKD-EPI formula

- Direct (conjugated) bilirubin ≤ 2.0 x ULN

- Alanine transaminase (ALT) ≤ 3.0 x ULN

7. Received standard age-appropriate care for SCD, including an up-to-date record of
immunizations, as per local requirements

8. Patients who are clinically stable and are in a non-crisis state at the time of
treatment start

Exclusion criteria

Patients eligible for this Treatment Plan must not meet any of the following criteria:

1. Contraindication or hypersensitivity to any drug or metabolites from similar class as
crizanlizumab drug or to any excipients of the drug formulation.

2. History of severe hypersensitivity reaction to other monoclonal antibodies, which in
the opinion of the Treating Physician may pose an increased risk of serious infusion
reaction.

3. Has documented immunogenicity to a prior biologic.

4. Pregnant or nursing women

5. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 15 weeks after stopping treatment. Highly effective
contraception methods include:

- Total abstinence (when this is in line with the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception

- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before
taking crizanlizumab. In case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment

- Male sterilization (at least 6 months prior to treatment). The vasectomized male
partner should be the sole partner for that patient

- Use of oral, injected or implanted hormonal methods of contraception or placement
of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of
hormonal contraception that have comparable efficacy (failure rate <1%), for
example hormone vaginal ring or transdermal hormone contraception.

- In case of use of oral contraception, women should have been stable on the same
pill for a minimum of 3 months before starting treatment.

- Women of child bearing potential must be informed that taking the study treatment
may involve unknown risks to the fetus if pregnancy were to occur during the
study and agree that in order to participate in the MAP they must adhere to the
contraception requirement for the duration of treatment.

6. Patients with bleeding disorders

7. Known history of testing positive for Human Immunodeficiency Virus (HIV) infection

8. Patients with active Hepatitis B infections (HBsAg positive)

- Note: Patients with antecedent but no active Hepatitis B (i.e. anti-HBc positive,
HBsAg and HBV-DNA negative) are eligible

9. Patients with positive test for hepatitis C ribonucleic acid (HCV RNA)

- Note: Patients in whom HCV infection resolved spontaneously (positive HCV antibodies
without detectable HCV-RNA) or those that achieved a sustained virological response
after antiviral treatment and show absence of detectable HCV RNA ≥ 6 months (with the
use of IFN-free regimes) or ≥ 12 months (with the use of IFN-based regimes) after
cessation of antiviral treatment are eligible

10. Significant active infection or immune deficiency (including chronic use of
immunosuppressive drugs)

11. Malignant disease. Exceptions to this exclusion include the following: malignancies
that were treated curatively and have not recurred within 2 years prior to treatment;
completely resected basal cell and squamous cell skin cancers and any completely
resected carcinoma in situ

12. Has a serious mental or physical illness, which, in the opinion of the Treating
Physician would compromise compliance to treatment.