ACCRUFeR® (ferric maltol) Was Proven Safe and Effective in Multiple Phase 3 Clinical Trials

Clinical Data, IBD
Clinical Data, CKD
MOA
Safety
Dosing

ACCRUFeR Demonstrated Significant Efficacy at 12 Weeks in Patients With IBD and Maintained Consistent Efficacy Over 64 Weeks1,2

  • 12 week data

    ACCRUFeR significantly increased change in hemoglobin from baseline in patients with inflammatory bowel disease (IBD) at week 12 vs placebo (P<0.0001) (AEGIS-IBD)1

    • The mean (SE) improvement in Hb in the ferric maltol group versus placebo was 2.25 (0.12) g/dL (one-sided 97.5% CI, 1.81; P<0.0001 based on ANCOVA)2

    ANCOVA, analysis of covariance. SE, standard error.

    Image showing how Accrufer significantly increased change in hemoglobin from baseline in patients with inflammatory bowel disease (IBD) at week 12 vs placebo (P<0.0001) (AEGIS-IBD)20

    In the responder analysis, 78% of ACCRUFeR patients had a ≥1 g/dL change in hemoglobin at week 12 vs 11% placebo1

    Pie chart image showing responder analysis - 78% of Accrufer patients had a ≥1 g/dL change in hemoglobin at week 12 vs 11% placebo
  • Extension Data

    Long-term efficacy in inflammatory bowel disease (IBD)2

    ACCRUFeR
    Mean hemoglobin concentrations (g/dL) increased from 11.0 at baseline to 13.95 at week 642
    Switched Patients
    Mean hemoglobin concentrations (g/dL) increased from 11.10 at baseline to 13.33 at week 642
    • The cumulative proportion of patients who maintained normal hemoglobin was 71% at week 12, 79.7% at week 24, and 86.1% at week 642
    • TSAT increased from 10% at baseline to 26% at week 16 and 29% at week 642
  • Study Description
     

    STUDY DESIGN

    • Two randomized, double-blind, placebo-controlled studies of IBD AEGIS 1: (58 ulcerative colitis patients, AEGIS 2: 70 Crohn’s disease) patients with iron deficiency anemia1 (N=128)
      • Secondary: Changes in hemoglobin concentration from baseline to weeks 4 and 8, serum ferritin concentration, and percentage transferrin saturation (TSAT)
    • Hemoglobin concentrations were between 9.5 g/ dL and 12 /13 g/dL for females/males and ferritin <30 μg/L. All patients had previously failed on treatment with oral ferrous replacement products1
    • Subjects were randomized 1:1 to receive either 30 mg ACCRUFeR twice daily or a matched placebo control for 12 weeks1
    • A responder analysis was done defining treatment responders as patients who achieved increases in hemoglobin of ≥1 g/dL or ≥2 g/dL, or hemoglobin normalization by week 12. Normalization of hemoglobin was defined based on hemoglobin values ≥12 g/dL for females or ≥13 g/dL for males20
    • A 52-week open-label extension, followed by a 14-day safety follow-up period of patients with IBD and iron deficiency anemia followed the pivotal trial (N=97) – 111 patients completed randomized 1:1 treatment with ACCRUFeR or placebo; 97 entered the open-label ferric maltol extension21
      • 111 patients completed randomized 1:1 treatment with ACCRUFeR or placebo; 97 entered the open-label ferric maltol extension21

    STUDY ENDPOINTS

    • Primary endpoint pivotal: The mean difference in hemoglobin concentration from baseline to week 12 between ACCRUFeR and placebo. The Least Squares [LS] mean difference from baseline was 2.18 g/dL (P<0.0001)1 – Secondary: Changes in hemoglobin concentration from baseline to weeks 4 and 8, serum ferritin concentration, and percentage transferrin saturation (TSAT)20
    • Primary endpoint extension: Absolute change in hemoglobin from baseline (day 0 of treatment), at the beginning of randomized therapy21

    STUDY PATIENTS BASELINE CHARACTERISTICS

    • Mean age: 38.5 to 40.1 years20
    • Gender and ethnicity: 40-43 years; 60-62% were white, 2-4% were other20

ACCRUFeR Statistically Increased Hemoglobin, Ferritin, and TSAT Levels in Patients With Stage 3 and 4 CKD by Week 16 and Improvements Were Maintained Over 52 Weeks3,4

  • 16 week data
    • ACCRUFeR had an LS mean difference in change from baseline hemoglobin of 0.13 g/dL at Week 4 and 0.46 g/dL at week 8 vs placebo3
    • ACCRUFeR increased hemoglobin, ferritin, and TSAT from baseline in stage 3 or 4 chronic kidney disease (CKD) patients at weeks 4, 8, and 16 and was consistent with changes seen in AEGIS-IBD studies3
    • The mean change in ferritin concentration from baseline to week 16 was 49.3 mcg/L for the ACCRUFeR group and 6.3 mcg/L for the placebo group (a mean difference of 43.0 mcg/L)3
    • At week 16, hemoglobin increased significantly by 0.5 g/dL with ferric maltol versus placebo (P=0.01)3
  • Extension Data

    In an open-label chronic kidney disease (CKD) extension study

    74% OF CKD PATIENTS

    completed the open-label treatment period4

  • Study Description
     

    STUDY DESIGN

    • Phase 3, double-blind, randomized, placebo-controlled trial of adults with stage 3-4 CKD and iron deficiency anemia for 16 weeks (N=167)1
    • Subjects were randomized 2:1 to receive either 30 mg ACCRUFeR twice daily or a matched placebo control1
    • All patients completing 16 weeks of double-blind treatment were offered to continue to receive ACCRUFeR in a 36-week open-label extension phase. Of the 167 patients randomized (ITT population), 125 started open-label ACCRUFeR, and 92 (74%) completed the open-label treatment period22

    STUDY ENDPOINTS

    • Primary: Mean difference in hemoglobin concentration from baseline to Week 16 between ACCRUFeR and placebo1
    • Secondary: Proportions of patients with hemoglobin increases of at least 1 g/dL and at least 2 g/dL at week 16; the proportion of patients achieving a hemoglobin concentration of at least 11.0 g/dL at week 16; change in hemoglobin concentration from baseline to weeks 4 and 8; and changes in ferritin, TSAT, and serum iron measures at weeks 4, 8, and 1622

    STUDY PATIENTS BASELINE CHARACTERISTICS

    • Mean age: mean age 65.5 to 68.5 years, range 30-90 years1
    • Gender and ethnicity: 50 males and 117 female; 81% white, 23% African American, and 7% other

ACCRUFeR Has a Unique Mechanism of Action3,5

  • Accrufer is a novel, low-dose, oral formulation of a non-salt complex of Fe3+, which is stable in the GI tract3,5
  • Accrufer is the only oral iron therapy made of ferric iron bound or chelated to maltol3
  • Unlike ferrous (Fe2+) iron, the absorption of ferric (Fe3+) maltol in the upper GI system may occur through a pathway or process not generally shared by other nutritional metals6
  • ACCRUFeR delivers an effective low dose of elemental iron (both over-the-counter and prescription) to successfully reverse IDA7
Image showing maltol molecules and how they remain tightly bound to Accrufer as it passes through the stomach, preventing formation of reactive oxygen species (ROS) including, eg, hydroxyl radicals

The maltol in ACCRUFeR remains tightly bound as it passes through the stomach, preventing formation of reactive oxygen species (ROS) including, eg, hydroxyl radicals.3,5

Image showing how Accrufer is not broken down in the stomach, which prevents formation of reactive oxygen species (eg hydroxyl radicals)

ACCRUFeR is not broken down in the stomach, which prevents formation of reactive oxygen species (eg, hydroxyl radicals).3,5

  • Clumping of free iron is lessened
  • Formation of ROS (eg, hydroxyl radicals) is prevented
Image showing how stable ferric maltol dissociates upon uptake of the GI tract, allowing iron and maltol to be absorbed separately

Stable ferric maltol dissociates upon uptake of the GI tract, allowing iron and maltol to be absorbed separately.3

Image showing iron is transported to the bone marrow for erythropoiesis; excess iron is excreted.

Iron is primarily transported to the bone marrow for erythropoiesis; excess iron is excreted.7,8

ACCRUFeR Was Shown to Be Safe and Well Tolerated Across Studies3

  • A high proportion of patients taking ACCRUFeR completed 12 and 16 weeks of treatment in both the IBD and CKD populations1,3
  • Neither short- or long-term ACCRUFeR treatment led to iron overload3

ONLY 4.6% of ACCRUFeR-treated patients discontinued treatment due to adverse reactions3,*

*Excludes the open-label extension period

Adverse reactions reported by ≥1% of patients treated with ACCRUFeR during double-blind phases of placebo-controlled period of pooled studies (Studies AEGIS 1 & 2 and AEGIS 3)3

A chart showing the body system adverse reaction gastrointestinal table comparing Accrufer data (30 mg bid, n=175) vs Placebo data (n=120).

ACCRUFeR Dosing3

Accrufer dosing image which shows 30mg capsules, dosing information, which states 2x daily, and information about not taking Accrufer with food for best results
  • Treatment duration depends on the severity of iron deficiency; at least 12 weeks of treatment is typically required
  • Treatment with ACCRUFeR should be continued as long as necessary until ferritin levels are within the normal range
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References

1. ACCRUFeR® full prescribing information. Shield Therapeutics, 2022. 2. Gasche C, Ahmad T, Zsolt T, et al. Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program. Inflamm Bowel Dis. 2015;21:579-588. 3. Schmidt C, Ahmad T, Tulassay Z, et al. Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long-term extension data from a Phase 3 study. Aliment Pharmacol Ther. 2016;44:259-270. 4. Pergola PE, Kopyt NP. Oral ferric maltol for the treatment of iron-deficiency anemia in patients with CKD: a randomized trial and open-label extension [published online ahead of print, May 21, 2021]. Am J Kidney Dis. 2021;S0272-6386(21)00624-7. 5. Harvey RS, Reffitt DM, Doig LA, et al. Ferric trimaltol corrects iron deficiency anaemia in patients intolerant of iron. Aliment Pharmacol Ther. 1998;12:845-848. 6. Conrad ME, Umbreit JN. Iron absorption and transport—an update. Am J Hematol. 2000;64(4):287-298. 7. Stallmach A, Büning C. Ferric maltol (ST10): a novel oral iron supplement for the treatment of iron deficiency anemia in inflammatory bowel disease. Expert Opin Pharmacother. 2015;16:2859-2867. 8. Papanikolaou G, Pantopoulos K. Systemic iron homeostasis and erythropoiesis. IUBMB Life. 2017;69(6):399-413.