WHAT%IS%

SiderAL%r.m.®?!

•  SiderAL®! r.m.$ represents! an! phospholipid2containig! carrier! in!which!ferric!pyrophosphate!is!protected!by!a!phospholipid!bilayer!membrane,!mainly!from!sunflower!lecithin,!plus!scuresters!matrix!

!!•  The!patented! technology! ensures!maximum! tolerability,! testless!!

and!total!absence!of!any!side!effect!that!is!commonly!associated!with!iron!supplementa@on.!!

•  Besides,!SiderAL®! r.m.$bypassing!normal! intes@nal!mechanism!of!absorp@on,! shows! an! increased! plasma! concentra@on,! beCer!than!usual!commercial!oral!iron!compounds.!!

Conven@onal!Iron!

Endocytosis!

Sucrosomial!Iron:!absorp@on!hypotesis!

SiderAL!r.m.$

Bloodstream! Lympha@c!stream!

15%%%

Enterocyte!

M!Cell!

Iron!release!into!the!liver!

The iron carried by phospholipid bilayer is not recognized as such, it is DIRECTLY ABSORBED, similar to chylomicrons, pass into the lymph and is carried to the liver

In&vitro&and%clinical%studies!

Bioavailability Sucrosomial Iron / Ferrous Sulfate The Sucrosomial Technology allows to increase the bioavailability

of SIDERAL

Randomized Phase II Trial of supplementation with oral liposomal iron versus intravenous iron in patients with chemotherapy-related anemia without Iron deficiency treated with Darbepoetin Alfa A. Mafodda1, D. Giuffrida2, A. Prestifilippo2, D. Azzarello1, P. Del Medico1, M. Mare2, R. Maisano1

1Oncologia Medica, A.O. B.M.M, Reggio Calabria – Italy 2Istituto Oncologico del Mediterraneo, Viagrande (Catania) – Italy

Background !Recombinant human erythropoietin (ESA) is the standard care for patients with chemotherapy related anemia. Intravenous (IV) iron improves hemoglobin (Hb) response with chemotherapy-associated anemia when combined with ESA. The concomitant use of oral iron as a supplement to ESA is controversial. In many studies intravenous iron produces a significantly greater increase in Hb level and erythropoietic response compared to oral iron. Our study evalueted the safety and efficacy of liposomial iron versus intravenous iron to increase hemoglobin in anemic cancer patients receiving chemotherapy and Darbepoietin Alfa..

Materials and Methods This prospective multicentric, randomized phase II study, enrolled 64 patients with chemotherapy-related anemia (Hb > 8 g/dl <10 g/dl) and no absolute or functional iron deficiency scheduled to receive chemotherapy and ESA. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of ferric gluconate 125 mg IV weekly or oral liposomal iron 30 mg daily. The primary endpoint was to demonstrate the non inferiority of oral liposomal iron in improving Hb response compared to intravenous iron. The Hb response was defined as the Hb increase ≥ 2 g/dl from baseline or the attainment Hb ≥ 12g/dl. Safety profile, red blood cell transfusion and quality of life was also evaluated

Results There was no difference in the Hb response rate between the two treatment arms. 71% of IV iron-treated patients achieved an erythropoietic response compared with 70% who received oral iron. Chi squared equals 0.014 with 1 degrees of freedom. The two-tailed P value equals 0.9060. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life. Liposomal oral iron was better tolerated.

Conclusion In cancer patients with chemotherapy related anemia receiving Darbepoietin Alfa, liposomial oral iron provides similar increase in Hb and Hb response with better tolerability and more convenient administration than IV iron.

Bibliography: •  Petrelli F et al., Addition of iron to erythropoiesis-stimulating

agents in cancer patients: a meta-analysis of randomized trials. J Cancer Res Clin Oncol. 2011 Oct 5

•  Tonelli M et al., Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ. 2009 May 26;180(11)

Darbepoietina + Sideral R.M.

n=33

Darbepoietina + I.V. n=31

Sex (%) Male Woman

13 (40%) 20 (60%)

12 (39%) 19 (61%)

Cancer (%) Breast Lung

10 (30%) 23 (70%)

10 (32%) 21 (68%)

Mean levels basal Hb 9.6 9.4

Chemotherapy Platinum (%) 10 (30%) 12 (38%)

Performance Status (%) 0 1 2

22 (66%) 10 (30%)

1 (3%)

19 (62%) 10 (32%)

2 (6%)

Darbepoietin + Sideral R.M.

n=33

Darbepoietin + Ferro i.v. n=31

Patients with adverse events (%) 13 (39%) 15 (48%)

Patients with serious adverse events (%) 2 (6%) 1 (3%)

Patients with gastrointestinal discomforts related to treatment (%)

1 (3%) 0

Patients with reaction after infusion of intravenous (%)

0 2 (6%)

Thromboembolic vascular events (%) 1 (3%) 1 (3%)

Fatal events All (%) Treatment-related (%)

1 (3%)

0

1 (3%)

0 Fig.1 Flow chart

Tab.1 Characteristics of the patients

Tab.2 Safety

Contacts: antoninomafodda@gmail.com

F07

Fig.2 Results

Randomized Phase II Trial of supplementation with oral liposomal iron versus intravenous iron in patients with chemotherapy-related anemia without Iron deficiency treated with Darbepoetin Alfa A. Mafodda1, D. Giuffrida2, A. Prestifilippo2, D. Azzarello1, P. Del Medico1, M. Mare2, R. Maisano1

1Oncologia Medica, A.O. B.M.M, Reggio Calabria – Italy 2Istituto Oncologico del Mediterraneo, Viagrande (Catania) – Italy

Background !Recombinant human erythropoietin (ESA) is the standard care for patients with chemotherapy related anemia. Intravenous (IV) iron improves hemoglobin (Hb) response with chemotherapy-associated anemia when combined with ESA. The concomitant use of oral iron as a supplement to ESA is controversial. In many studies intravenous iron produces a significantly greater increase in Hb level and erythropoietic response compared to oral iron. Our study evalueted the safety and efficacy of liposomial iron versus intravenous iron to increase hemoglobin in anemic cancer patients receiving chemotherapy and Darbepoietin Alfa..

Materials and Methods This prospective multicentric, randomized phase II study, enrolled 64 patients with chemotherapy-related anemia (Hb > 8 g/dl <10 g/dl) and no absolute or functional iron deficiency scheduled to receive chemotherapy and ESA. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of ferric gluconate 125 mg IV weekly or oral liposomal iron 30 mg daily. The primary endpoint was to demonstrate the non inferiority of oral liposomal iron in improving Hb response compared to intravenous iron. The Hb response was defined as the Hb increase ≥ 2 g/dl from baseline or the attainment Hb ≥ 12g/dl. Safety profile, red blood cell transfusion and quality of life was also evaluated

Results There was no difference in the Hb response rate between the two treatment arms. 71% of IV iron-treated patients achieved an erythropoietic response compared with 70% who received oral iron. Chi squared equals 0.014 with 1 degrees of freedom. The two-tailed P value equals 0.9060. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life. Liposomal oral iron was better tolerated.

Conclusion In cancer patients with chemotherapy related anemia receiving Darbepoietin Alfa, liposomial oral iron provides similar increase in Hb and Hb response with better tolerability and more convenient administration than IV iron.

Bibliography: •  Petrelli F et al., Addition of iron to erythropoiesis-stimulating

agents in cancer patients: a meta-analysis of randomized trials. J Cancer Res Clin Oncol. 2011 Oct 5

•  Tonelli M et al., Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ. 2009 May 26;180(11)

Darbepoietina + Sideral R.M.

n=33

Darbepoietina + I.V. n=31

Sex (%) Male Woman

13 (40%) 20 (60%)

12 (39%) 19 (61%)

Cancer (%) Breast Lung

10 (30%) 23 (70%)

10 (32%) 21 (68%)

Mean levels basal Hb 9.6 9.4

Chemotherapy Platinum (%) 10 (30%) 12 (38%)

Performance Status (%) 0 1 2

22 (66%) 10 (30%)

1 (3%)

19 (62%) 10 (32%)

2 (6%)

Darbepoietin + Sideral R.M.

n=33

Darbepoietin + Ferro i.v. n=31

Patients with adverse events (%) 13 (39%) 15 (48%)

Patients with serious adverse events (%) 2 (6%) 1 (3%)

Patients with gastrointestinal discomforts related to treatment (%)

1 (3%) 0

Patients with reaction after infusion of intravenous (%)

0 2 (6%)

Thromboembolic vascular events (%) 1 (3%) 1 (3%)

Fatal events All (%) Treatment-related (%)

1 (3%)

0

1 (3%)

0 Fig.1 Flow chart

Tab.1 Characteristics of the patients

Tab.2 Safety

Contacts: antoninomafodda@gmail.com

F07

Fig.2 Results

Randomized Phase II Trial of supplementation with oral liposomal iron versus intravenous iron in patients with chemotherapy-related anemia without Iron deficiency treated with Darbepoetin Alfa A. Mafodda1, D. Giuffrida2, A. Prestifilippo2, D. Azzarello1, P. Del Medico1, M. Mare2, R. Maisano1

1Oncologia Medica, A.O. B.M.M, Reggio Calabria – Italy 2Istituto Oncologico del Mediterraneo, Viagrande (Catania) – Italy

Background !Recombinant human erythropoietin (ESA) is the standard care for patients with chemotherapy related anemia. Intravenous (IV) iron improves hemoglobin (Hb) response with chemotherapy-associated anemia when combined with ESA. The concomitant use of oral iron as a supplement to ESA is controversial. In many studies intravenous iron produces a significantly greater increase in Hb level and erythropoietic response compared to oral iron. Our study evalueted the safety and efficacy of liposomial iron versus intravenous iron to increase hemoglobin in anemic cancer patients receiving chemotherapy and Darbepoietin Alfa..

Materials and Methods This prospective multicentric, randomized phase II study, enrolled 64 patients with chemotherapy-related anemia (Hb > 8 g/dl <10 g/dl) and no absolute or functional iron deficiency scheduled to receive chemotherapy and ESA. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of ferric gluconate 125 mg IV weekly or oral liposomal iron 30 mg daily. The primary endpoint was to demonstrate the non inferiority of oral liposomal iron in improving Hb response compared to intravenous iron. The Hb response was defined as the Hb increase ≥ 2 g/dl from baseline or the attainment Hb ≥ 12g/dl. Safety profile, red blood cell transfusion and quality of life was also evaluated

Results There was no difference in the Hb response rate between the two treatment arms. 71% of IV iron-treated patients achieved an erythropoietic response compared with 70% who received oral iron. Chi squared equals 0.014 with 1 degrees of freedom. The two-tailed P value equals 0.9060. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life. Liposomal oral iron was better tolerated.

Conclusion In cancer patients with chemotherapy related anemia receiving Darbepoietin Alfa, liposomial oral iron provides similar increase in Hb and Hb response with better tolerability and more convenient administration than IV iron.

Bibliography: •  Petrelli F et al., Addition of iron to erythropoiesis-stimulating

agents in cancer patients: a meta-analysis of randomized trials. J Cancer Res Clin Oncol. 2011 Oct 5

•  Tonelli M et al., Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ. 2009 May 26;180(11)

Darbepoietina + Sideral R.M.

n=33

Darbepoietina + I.V. n=31

Sex (%) Male Woman

13 (40%) 20 (60%)

12 (39%) 19 (61%)

Cancer (%) Breast Lung

10 (30%) 23 (70%)

10 (32%) 21 (68%)

Mean levels basal Hb 9.6 9.4

Chemotherapy Platinum (%) 10 (30%) 12 (38%)

Performance Status (%) 0 1 2

22 (66%) 10 (30%)

1 (3%)

19 (62%) 10 (32%)

2 (6%)

Darbepoietin + Sideral R.M.

n=33

Darbepoietin + Ferro i.v. n=31

Patients with adverse events (%) 13 (39%) 15 (48%)

Patients with serious adverse events (%) 2 (6%) 1 (3%)

Patients with gastrointestinal discomforts related to treatment (%)

1 (3%) 0

Patients with reaction after infusion of intravenous (%)

0 2 (6%)

Thromboembolic vascular events (%) 1 (3%) 1 (3%)

Fatal events All (%) Treatment-related (%)

1 (3%)

0

1 (3%)

0 Fig.1 Flow chart

Tab.1 Characteristics of the patients

Tab.2 Safety

Contacts: antoninomafodda@gmail.com

F07

Fig.2 Results

Randomized Phase II Trial of supplementation with oral liposomal iron versus intravenous iron in patients with chemotherapy-related anemia without Iron deficiency treated with Darbepoetin Alfa A. Mafodda1, D. Giuffrida2, A. Prestifilippo2, D. Azzarello1, P. Del Medico1, M. Mare2, R. Maisano1

1Oncologia Medica, A.O. B.M.M, Reggio Calabria – Italy 2Istituto Oncologico del Mediterraneo, Viagrande (Catania) – Italy

Background !Recombinant human erythropoietin (ESA) is the standard care for patients with chemotherapy related anemia. Intravenous (IV) iron improves hemoglobin (Hb) response with chemotherapy-associated anemia when combined with ESA. The concomitant use of oral iron as a supplement to ESA is controversial. In many studies intravenous iron produces a significantly greater increase in Hb level and erythropoietic response compared to oral iron. Our study evalueted the safety and efficacy of liposomial iron versus intravenous iron to increase hemoglobin in anemic cancer patients receiving chemotherapy and Darbepoietin Alfa..

Materials and Methods This prospective multicentric, randomized phase II study, enrolled 64 patients with chemotherapy-related anemia (Hb > 8 g/dl <10 g/dl) and no absolute or functional iron deficiency scheduled to receive chemotherapy and ESA. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of ferric gluconate 125 mg IV weekly or oral liposomal iron 30 mg daily. The primary endpoint was to demonstrate the non inferiority of oral liposomal iron in improving Hb response compared to intravenous iron. The Hb response was defined as the Hb increase ≥ 2 g/dl from baseline or the attainment Hb ≥ 12g/dl. Safety profile, red blood cell transfusion and quality of life was also evaluated

Results There was no difference in the Hb response rate between the two treatment arms. 71% of IV iron-treated patients achieved an erythropoietic response compared with 70% who received oral iron. Chi squared equals 0.014 with 1 degrees of freedom. The two-tailed P value equals 0.9060. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life. Liposomal oral iron was better tolerated.

Conclusion In cancer patients with chemotherapy related anemia receiving Darbepoietin Alfa, liposomial oral iron provides similar increase in Hb and Hb response with better tolerability and more convenient administration than IV iron.

Bibliography: •  Petrelli F et al., Addition of iron to erythropoiesis-stimulating

agents in cancer patients: a meta-analysis of randomized trials. J Cancer Res Clin Oncol. 2011 Oct 5

•  Tonelli M et al., Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ. 2009 May 26;180(11)

Darbepoietina + Sideral R.M.

n=33

Darbepoietina + I.V. n=31

Sex (%) Male Woman

13 (40%) 20 (60%)

12 (39%) 19 (61%)

Cancer (%) Breast Lung

10 (30%) 23 (70%)

10 (32%) 21 (68%)

Mean levels basal Hb 9.6 9.4

Chemotherapy Platinum (%) 10 (30%) 12 (38%)

Performance Status (%) 0 1 2

22 (66%) 10 (30%)

1 (3%)

19 (62%) 10 (32%)

2 (6%)

Darbepoietin + Sideral R.M.

n=33

Darbepoietin + Ferro i.v. n=31

Patients with adverse events (%) 13 (39%) 15 (48%)

Patients with serious adverse events (%) 2 (6%) 1 (3%)

Patients with gastrointestinal discomforts related to treatment (%)

1 (3%) 0

Patients with reaction after infusion of intravenous (%)

0 2 (6%)

Thromboembolic vascular events (%) 1 (3%) 1 (3%)

Fatal events All (%) Treatment-related (%)

1 (3%)

0

1 (3%)

0 Fig.1 Flow chart

Tab.1 Characteristics of the patients

Tab.2 Safety

Contacts: antoninomafodda@gmail.com

F07

Fig.2 Results

BACKGROUND:%Sucrosome!has!a!described!an@2inflammatory!effect!and!transports!its!content!directly!in!blood,!beyond!gastric!and!enteric!wall.!

SUCROSOMIAL%IRON%IS%BETTER%THAN%IRON%SULFATE%IN%CORRECTION%OF%ANEMIA%OF%CHRONIC%INFLAMMATORY%DISEASE%OF%YOUNG%WOMEN%

%Giordano&G&1,&D'Amico&F&5,&D'Aveta&A&5,&De&Maria&M&5,Perro9a&N&2,Sansò&C&3,Berardi&G&4,&Carabellese&B&1&

1Osp.$"Cardarelli"$Campobasso,$2$Univ.$"G.$D'annunzio"$Chie=,$3$UCSC$Roma,$4$MMG$Campobasso,$5Fondazione$"G.$Paolo$II"$Campobasso%

AIM:%Aim!of!this!study!is!to!verify!if!Sucrosomial!iron!is!most!effec@ve!than!iron!sulfate!in!correc@on!of!anemia!of!chronic!inflammatory!disease!of!young!women!

PATIENTS%AND%METHODS:% In! group!A! 9! pa@ents! (4!with! systemic! erythematous! lupus,! 3!with!mixed! connec@vi@s,! 2!with! rheuma@c!fibromyalgia),!median!age!32!years!(R27242),!Hb!8.5!g/dl!(R8210),!satura@on!of!iron!binding!capacity!<!20%,!with!a!median!ferri@n!level!of!100!ng/ml!(R902250),!ESR!35!mm/1st!hour!(R22295),!CRP!18!mg/I!(R12224),!normal!B12!and!folate,!received!Sucrosomial!iron!60!mg/day!orally!for!3!months.!In!group!B!12!pa@ents!(6!with!systemic!erythematous!lupus,!3!with!mixed!connec@vi@s,!3!with!rheuma@c!fibromyalgia),!median!age!38!years!(R29245),!Hb!9!g/dl!(R829.5),!satura@on!of!iron!binding!capacity!<!20%,!with!a!median!ferri@n!level!of!120!ng/ml!(R802190),!ESR!33!mm/1st!hour!(R20287),!CRP!15!mg/I!(R13227),!normal!B12!and!folate,!received!iron!sulfate!210!mg/day!orally!for!3!months.!%RESULTS:!A]er!treatment,!group!A!showed!a!median!hemoglobin! level!of!11.5!g/dl! (R10.5212),!a!median!ferri@n! level!of!260!ng/ml!(R!1902280),!a!ESR!decrease!to!a!median!value!of!8!mm/1st!hour!(R!3210)!and!a!median!CRP!3!mg/I!(R224).!A]er!treatment,!group!B!showed!a!median!hemoglobin!level!of!9.5!g/dl!(R829.5),!a!median!ferri@n!level!of!100!ng/ml!(R!902180),!and!ESR!and!CRP!don’t!showed!any!improvement.!4!pa@ents!showed!hepygastralgia,!2!s@psis,!5!diarrohea.!

Published!as!Abstract!at!SIE!(Italian!Society!of!Hematology)!Congress!2013!

CONCLUSIONS%Sucrosomial%iron%is%most%safe,%effecNve,%well%tolerated,%effecNve%than%iron%sulfate%in%increase%hemoglobin%level%and%reduce%

inflammatory%markers%in%correcNon%of%anemia%of%chronic%inflammatory%disease%of%young%women.%

SiderAL r.m. is suitable for everybody:

•  Those who have an increased need or reduced dietary intake of iron

•  Women during pregnancy and lactation •  Vegetarians •  People with malabsorption diseases •  Celiac people (gluten-free) •  Diseases that cause chronic anemia (bleeding

disorders, IBD, cancer, kidney failure, etc.)

PEOPLE CAN FINALLY OVERCOME ANEMIA OR IRON DEFICIENCY WITHOUT SIDE EFFECTS