Efficacy and Safety of Ferriprox® in Patients With Sickle Cell Disease or Other Anemias

Deferiprone (brand name Ferriprox®) is an iron chelator that is approved in the United States
and over 60 other countries for the treatment of iron overload in patients with thalassemia,
when other treatments are inadequate. This study has been designed to evaluate the efficacy,
safety, and tolerability of deferiprone vs. deferoxamine in patients who have SCD or other
anemias, and who require chelation because of the extra iron they are taking in through blood
transfusions.

About 300 people from North America, South America, Europe, and the Middle East will take
part in this study. Participants will be randomized in a 2:1 ratio to receive therapy for 52
weeks with either deferiprone or deferoxamine, another type of iron chelator. Patients who
are randomized to the deferiprone group can choose to get the drug as either tablets or
liquid, and must take it three times daily. Patients who are randomized to the deferoxamine
group will receive it as a subcutaneous infusion that lasts from 8 to 12 hours and is given 5
to 7 days per week. For both drugs, the starting dosage is based on how much extra iron they
have taken in through transfusions in the last 3 months and on the severity of iron load, as
measured by serum ferritin levels in the blood and by the amount of iron in the liver and the
heart. For deferiprone, the starting dosage will be increased each week over the first 3
weeks; and for both drugs, the dosage may be adjusted up or down during the study based on
the level of iron overload and on safety considerations.

Patients will need to have their blood count checked every week for the first 26 weeks, then
every other week for the remaining 26 weeks; they will also have to give a blood sample for
more detailed safety testing every month; and to give a blood sample for the measurement of
serum ferritin every 3 months. Every six months, they will undergo an ECG and an MRI scan,
and will be asked to complete a quality of life survey.

At the end of the 52 weeks, participants will be invited to enter a 2-year study in which all
patients will receive deferiprone, including those who were randomized to receive
deferoxamine in the first year.

Inclusion Criteria:

1. Male or female ≥ 2 years of age;

2. Have sickle cell disease (confirmed by Hb electrophoresis or more specific tests) or
other conditions with iron overload from repeated blood transfusions (see exclusion
criteria for exceptions);

3. Baseline LIC >7 mg/g dw (measured by MRI);

4. Patients who have received no less than 20 transfusions of RBCs;

5. Patients who have received at least 1 transfusion per year in the last 2 years and who
are expected to have a continuing requirement (based on Investigator's judgement)
during the duration of the trial

Exclusion Criteria:

1. Thalassemia syndromes;

2. Myelodysplastic syndrome (MDS) or myelofibrosis;

3. Diamond Blackfan anemia;

4. Primary bone marrow failure;

5. Baseline LIC >30 mg/g dw (measured by MRI);

6. Unable or unwilling to undergo a 7 day washout period if currently being treated with
deferiprone or deferoxamine or deferasirox;

7. Previous discontinuation of treatment with deferiprone or deferoxamine due to adverse
events;

8. History or presence of hypersensitivity or idiosyncratic reaction to deferiprone or
deferoxamine;

9. Treated with hydroxyurea within 30 days;

10. History of malignancy;

11. Evidence of abnormal liver function (serum ALT level(s) > 5 times upper limit of
normal at screening or creatinine levels >2 times upper limit of normal at screening);

12. A serious, unstable illness, as judged by the Investigator, during the past 3 months
before screening/baseline visit including but not limited to: hepatic, renal,
gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or
immunologic disease;

13. Clinically significant abnormal 12-lead ECG findings;

14. Cardiac MRI T2* <10ms;

15. Myocardial infarction, cardiac arrest or cardiac failure within 1 year before
screening/baseline visit;

16. Unable to undergo MRI

17. Presence of metallic objects such as artificial joints, inner ear (cochlear) implants,
brain aneurysm clips, pacemakers, and metallic foreign bodies in the eye or other body
areas that would prevent use of MRI imaging