HepaSphereTM Microspheres…Compelling Advantages for Drug-Eluting TACE

AdvAntAge: drug loading throughout the entire spherical volume

Consistent loading throughout the sphere offers potential for optimal drug loading and delivery.Cross section of HepaSphere Microspheres loaded with doxorubicin originally taken at 20x magnification. The red color indicates the presence of doxorubicin. Data on file at BioSphere Medical.

AdvAntAge: effective tumor cell “kill” rate vs. bland embolization

AdvAntAge: Penetration of doxorubicin into surrounding tissue

In a vX-2 animal model, HepaSphere 50-100µm Microspheres eluted doxorubicin to a distance of up to1600 microns into the surrounding tumor tissue assessed 24 hours after delivery1.

AdvAntAge: encouraging initial clinical experience with HepaSphere Microspheres in HCC Patients3

n 50, Child-Pugh A/BLoading 50 mg# treatments Up to 3Follow-up Interval 6 monthsObjective Response 77.4%

note: not controlled, not randomized, 4 sites, doxorubicin or epirubicin

AdvAntAge: Low systemic drug exposure of doxorubicin

AdvAntAge: Sustains greater tumoral concentration of doxorubicin within tumor vs. outside of tumor

Plasma concentration of doxorubicin and doxorubicinol of HepaSphere loaded microspheres in a VX‐2 model

Plasma concentration of doxorubicin and doxorubicinol of HepaSphere loaded microspheres in a VX-2 model2

Intra-tumoral/peri-tumoral concentration of doxorubicin loaded HepaSphere Microspheres in a VX-2 model2

Intra‐tumoral/peri‐tumoral concentration of doxorubicin loaded HepaSpheres in a VX‐2 model

1 Gupta et al. “Hepatic Arterial Embolization with Doxorubicin-Loaded Superabsorbent Polymer Microspheres in a Rabbit Liver Tumor Model.” Cardiovasc Intervent Radiol 2011; 34(5):1021-30.2 Lee et al. “Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer.” Cardiovasc Intervent Radiol 2010; 33(3):576-82.3 Grosso et al. “Transarterial Chemoembolization for Hepatocellular Carcinoma with Drug-Eluting Microspheres: Preliminary Results from an Italian Multicentre Study.” Cardiovasc Intervent Radiol 2008; 31:1141-49.

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levels at 3 days after treatment, suggesting rapid elution of

doxorubicin from the tumor. This finding is further cor-

roborated by the finding that although animals killed 1 day

after TACE showed tumor fluorescence, none of the ani-

mals killed 3 or 7 days after TACE had appreciable tumor

fluorescence, suggesting that very little drug remained in

the tumors at these times. Based on these results, we

believe that although the use of standard TACE with

Lipiodol allows greater tumor doxorubicin deposition than

the use of HAI, TACE plus Lipiodol does not prolong

doxorubicin retention in the tumor for more than 24 h after

treatment.

The lower plasma doxorubicin concentrations in the

QuadraSphere group compared with other treatment

groups, as seen in the current study, demonstrate higher

tumor retention of the drug in the animals treated with

QuadraSpheres. Lower plasma doxorubicin levels in the

QuadraSphere group also has the potential benefit of

reducing systemic exposure to the chemotherapeutic drug,

which could allow administration of higher concentrations

of doxorubicin to the tumor. The pharmacokinetic profile

of plasma doxorubicinol in the QuadraSphere group, i.e.,

sustained levels from 10 min until 24 h after treatment,

also favors the slow drug-release feature of the

Fig. 4 Doxorubicin fluorescence in the QuadraSphere group. Photomicrographs (original magnification, 109) in animals euthanized 1 (A), 3(B), 7 (C), or 14 (D) days after treatment show fluorescence in and around the microspheres. The fluorescence intensity was similar at all times

Fig. 5 Doxorubicin fluorescence in the transarterial chemoemboli-

zation (TACE) group. Intratumoral fluorescence in an animal killed

1 day (A) after treatment (original magnification, 109). Minimal or

no intratumoral fluorescence is seen in animals killed at 3 days (B) or7 days (C) after treatment. Note the Embospheres in B and C

S. Gupta et al.: Hepatic Embolization with Doxorubicin-Loaded Microspheres

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10X With kind permission from Springer Science and Business Media

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16 pt 8 pt 0 pt 7 ptProgression

77.4%

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