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The ZAGAL Study : Long- term Management and Follow -up

FEETEG. The ZAGAL Study : Long- term Management and Follow -up of use of Miglustat in type 1 Gaucher disease in Spain. Pilar Giraldo Haematology Department . Miguel Servet University Hospital. Disclosures.

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The ZAGAL Study : Long- term Management and Follow -up

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  1. FEETEG The ZAGAL Study: Long-term Management and Follow-up of use of Miglustat in type 1 Gaucher disease in Spain. Pilar Giraldo HaematologyDepartment. Miguel Servet University Hospital

  2. Disclosures • Received reimbursement of expenses and honoraria for lectures and occasional consultancies on the management of Gaucher disease, from Protalix, Genzyme, Actelion and Shire June 29th 2012

  3. The ZAGAL Study • Design • Efficacy • Safety • Recommendations June 29th 2012

  4. ZAGAL study. (Zavesca en GaucherLeve) • After approval miglustat in EU (2004) • Objectives • To establish a set of recommendations for collecting safety, efficacy and QoL data (12 months and longer follow-up) • To guarantee the safe and proper use of miglustat in everyday clinical use • Treatment • Followed the recommendations of the European Working Group on Gaucher Disease Advisory Council June 29th 2012

  5. ZAGAL study 350 92 Total 442 RST 12.6% Mean: 3.1 y Age at diagnosis W&W28.7% Type of therapy Giraldo P et al OrphanetJ RareDis. 2012 June 29th 2012

  6. ZAGAL study General characteristics GD1 patients treated with miglustat according tolerance June 29th 2012

  7. ZAGAL study Platelets x109/L Hb g/dL 15 15 41 41 52 38 33 30 24 20 52 38 33 30 24 20 Years SpleenvolumemL LivervolumemL 15 41 52 38 33 30 24 20 15 41 52 38 33 30 24 20 June 29th 2012

  8. ZAGAL study QT nMol/mL.h CCL18/PARC ng/mL 15 15 41 41 52 38 33 30 24 20 52 38 33 30 24 20 Years June 29th 2012

  9. ZAGAL study S-MRI pattern Score • Non-homogeneous diffuse 3 • Non-homogeneous mottled 2 • Non-homogeneous reticular 1 • Normal 0 • Homogeneous 4 • Complications: bone infarct, avascular necrosis, bone crisis and vertebral collapse 4 June 29th 2012 Roca M et al Eur J Radiol. 2007

  10. ZAGAL study. Bone marrow changes after 2 years of miglustat SE T1 at baseline Non-homogeneous diffuse pattern Involvement of left trochanter A. Baseline B. 2 years SE T1 after 12 months on miglustat Non-homogeneous mottled pattern showing a perceptive change with increase of signal in both trochanters Roca et al., (unpublished observations) In Pastores GM et al 2008 REMARKS:Bone marrow-MRI improvement in naïve patients June 29th 2012 Roca M et al. Eur J Radiol. 2007;62:132-7.

  11. S-MRI TRAP-5b 15 25 20 10 Score U/L 15 10 5 5 0 0 1 2 3 4 5 6 7 1 2 3 4 5 6 7 CCL18/PARC Chitotriosidase 12000 1500 10000 8000 1000 ng/mL nM/mL.h 6000 500 4000 200 0 0 1 2 3 4 5 6 7 1 2 3 4 5 6 7 • ZAGAL study. Bone marrow changes after 2 years of miglustat Baseline 2 years June 29th 2012

  12. ZAGAL study June 29th 2012

  13. Quality of life: SF-36 scales June 29th 2012

  14. ZAGAL study Changes in the atherogenic profile of patients with type 1 Gaucher disease after miglustat therapy. In 26 GD1 patients treated with miglustat for up to 36 months: Group A: 10 patients therapy-naïve significantly: plasma HDL-c and apoA-I, and slightly increased TC; TG, CRP concentrations, and TC/HDL-c ratios decreased significantly Group B: 16 patients switched from enzyme replacement therapy (ERT); No changes in HDL-c and apoA-I, or in the TC/HDL-c ratio. CRP was observed after 12 months. LDL-c and apoB were not significantly altered in either patient group Miglustat appears to have beneficial effects on plasma lipid, lipoprotein, and CRP concentrations in therapy-naïve GD1 patients, resulting in an improved atherogenic lipid profile. . Puzo J et al Atherosclerosis. 2010 June 29th 2012

  15. ZAGAL study • In summary: 42 patients are on miglustat therapy and 15 patients have more than 7 years under therapy. • The goals of therapy have been achieved. • 3 patients died by non-related causes (2 neoplasia and 1 hearth attack), • 1 patient have discontinued by planning to become pregnant • 6 discontinuing by poor filling or intolerance. • 8 patients had transitory diarrhea and flatulence. June 29th 2012

  16. ZAGAL study. Adverse eventsand discontinuation June 29th 2012

  17. ZAGAL study. Recommendations • In ordertoavoid gastrointestinal disturbancesduringMiglustattherapy, we are recommendingtwostrategies: • Toadministratetherapywithoutmealsforexample 2 hoursbeforebreakfast, lunch and dinner • Tostarttherapy in scalating doses: • duringthefirstweekonly 100 mg /day • duringthesecondweekonly 200 mg/day • duringthirdweek and later total therapywith 300 mg/day • Simultaneouslyitisconvennientconsiderthecontent of carbohidrates in thedietaccordingthefollowingsuggestions: Giraldo P et al. Haematologica. 2009;94(12):1771-1775. June 29th 2012

  18. DietaryRecommendations June 29th 2012

  19. DietaryRecommendations June 29th 2012

  20. DietaryRecommendations June 29th 2012

  21. DietaryRecommendations June 29th 2012

  22. DietaryRecommendations June 29th 2012

  23. DietaryRecommendations June 29th 2012

  24. DietaryRecommendations June 29th 2012

  25. FEETEG

  26. FEETEG PilarGiraldo Sº Hematología. HU Miguel Servet

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