Investigators present final efficacy and tolerability data for study in children with a new liquid formulation of deferiprone (Ferriprox®)

Toronto, October 15, 2008 - ApoPharma Inc. today announced the presentation by investigators of final study data on a new liquid formulation of the iron chelator deferiprone (Ferriprox®) at the combined 11th International Conference on Thalassaemia & Haemoglobinopathies / 13th International TIF Conference for Thalassaemia Patients & Parents in Singapore from October 8-11, 2008.

Dr. Amal El-Beshlawy from the Pediatric Hospital at Cairo University in Cairo, Egypt presented a poster entitled 'The safety and efficacy of a new formulation of deferiprone (Ferriprox®) in children with transfusional iron overload'.

Dr. El-Beshlawy commented that the oral solution reduced serum ferritin levels successfully over the 24 week study period, was tolerated well with no unexpected adverse reactions. The data currently available also suggested that there was lower incidence of gastrointestinal adverse reactions than what has been reported with the tablet formulation of Ferriprox®. As a result, the development of Ferriprox® oral solution appears to represent an important opportunity to help young patients comply with chelation therapy in a safe and effective manner.

Preliminary data had been presented at the 13th European Hematology Association (EHA) meeting in Copenhagen on June 12th, 2008.

Study design
A 24 week, multi-centre, open label, single treatment study was conducted in 3 countries having young children with iron overload requiring iron chelation. Written consent was provided by the child's guardian. The protocol was approved by local IRBs. Inclusion criteria:

1. ≤ 10 years of age
2. confirmed diagnosis of transfusion-dependent anemia other than Blackfan-Diamond anemia
3. chronic iron overload requiring chelation therapy
4. enrolment in a chronic transfusion program, having received at least 8 red blood cell transfusions/year for a minimum of 1 year
5. serum ferritin (SF) concentration > 1,000 µg/L

Therapy was initiated at 50 mg/kg/day Ferriprox® divided in 3 doses, for the first 2 weeks, then increased to 75 mg/kg/d. The dose could be further increased to 100 mg/kg/day for patients with ferritin > 2500 µg/L at baseline.

Assessment of adverse events (AEs), concomitant medications, and CBC were performed weekly. Serum ALT, creatinine and zinc concentration were measured at baseline, week 12 and end of study. Serology for HCV and HBV were assessed at baseline and end of study. Serology for HIV was assessed at baseline only. Other safety assessments included medical history, physical examination and ECG.

Serum ferritin concentration was measured at baseline and every 4 weeks. The efficacy endpoint was the change in serum ferritin (SF) concentration from baseline.
Ferriprox® was to be discontinued upon onset of moderate or severe neutropenia/agranulocytosis. Ferriprox® was not discontinued at episodes of minor neutropenia and the neutrophil count was monitored daily until resolution of the event or progression to moderate neutropenia/agranulocytosis.

Study results- efficacy
100 patients enrolled; 54 Males / 46 Females (76 Caucasian [Egyptian], 24 Asian [9 Chinese, 13 Indonesian, 2 Malays]). Chelation therapy prior to study enrollment was deferasirox (8%), deferiprone (20%), and deferoxamine (52%) with the remaining children (20%) naïve to chelation therapy. The mean ± SD baseline SF for all patients was 2522 ±1459 μg/L.

After 24 weeks on Ferriprox® therapy, there was a significant (-356 +/- 978) reduction in SF values from baseline.

Study results- safety
95 patients completed the study with: 2 patients withdrawn due to AE; 1 lost to follow-up; and 2 voluntarily withdrawn). Two patients experienced agranulocytosis. One had experienced 2 previous episodes of mild neutropenia, which had resolved without discontinuation of Ferriprox®. At onset of ANC < 1.0 x 109/L, both patients discontinued deferiprone and were treated with GCSF. Resolution, defined as ANC counts > 1.5 x 109 /L for 2 consecutive days, occurred within 7 to 10 days for these patients. A further 6 patients experienced episodes of mild neutropenia and had their ANC monitored daily. All episodes resolved within 3-11 days, despite continued therapy with deferiprone. None progressed to agranulocytosis.
Gastrointestinal adverse reactions included reports of vomiting in 5% of patients, abdominal pain in 6% of patients and nausea in 1% of patients. Other reported adverse drug reactions included: neutrophil count decreased (16%); ALT increased (12%); increased appetite (5%); arthralgia (4%).

About ApoPharma
ApoPharma is the innovative drug development member of the Canadian-owned Apotex Group of Companies. ApoPharma is developing medications primarily in the fields of Iron Chelation and psoriasis.