Efficacy

Revestive delivered reductions in parenteral nutrition/IV fluids
with some patients achieving complete freedom from parenteral
nutrition/IV fluids1-6

Adults with short bowel syndrome-intestinal failure

Revestive has been studied in two, 24 week, phase III trials in adults.1

In STEPS/STEP-2, in adults with Short Bowel Syndrome-IF Revestive delivered sustained reductions in parenteral nutrition/IV fluids2,3

STEPS1,2

A randomised, double-blind, placebo-controlled Phase III trial including 86 adult patients with short bowel syndrome-intestinal failure (SBS-IF), who were dependent on parenteral nutrition/IV fluids (PN/IV) for at least 12 months prior to start of the study.

  • The primary efficacy endpoint was the proportion of patients who achieved a ≥20% reduction from baseline in weekly PN/IV volume at both Week 20 and Week 24
  • Secondary endpoints included the proportion and absolute change in PN/IV and the number of patients who stopped PN/IV and their time of discontinuation
  • Exploratory endpoints included reduction in days on PN/IV

STEPS 21,3

A 2-year, open-label, multicentre extension study of STEPS. The primary objective was to study long-term safety and efficacy of Revestive.

  • Safety variables included adverse events, laboratory data, vital signs, body weight, and colonoscopy
  • Efficacy endpoints included the proportion of patients achieving a response (≥20% reduction from baseline weekly PN/IV), duration of response, reduction in days of PN/IV per week, and number of patients who achieved independence from PN/IV

AT 6 MONTHS A SIGNIFICANT PROPORTION OF PATIENTS RESPONDED TO REVESTIVE

  • 63% of Revestive-treated patients achieved at least a 20% reduction from baseline in weekly PN/IV volume*1

-vs. 30% with placebo p=0.002

REVESTIVE DELIVERED SUSTAINED REDUCTIONS IN PN/IV**2,3

  • PN/IV reductions were seen as early as Week 4, and continued for up to 30 months in a post-hoc analysis of completers**2,3

WITH LONGER TERM TREATMENT, REVESTIVE GAVE PATIENTS FREEDOM FROM PARENTERAL NUTRITION/IV FLUIDS (PN/IV )**3

In a post-hoc analysis of completers, in patients completing 30 months of treatment***3

33% (10/30) achieved complete independence from PN/IV

60% (18/30) of Revestive treated patients achieved at least 3 day each week off PN/IV

70% (21/30) of Revestive treated patients achieved at least 1 day each week off PN/IV

Days off PN/IV may allow adult patients more independence and freedom7-9

Children with short bowel syndrome-intestinal failure

IN A 24-WEEK STUDY IN CHILDREN WITH SBS-IF, REVESTIVE DELIVERED REDUCTIONS IN PARENTERAL NUTRITION/IV FLUIDS6

A 24-week Phase III trial in children aged 1–17 years-old, who were dependent on PN/IV for at least 3 months, including 50 patients treated with Revestive (n=26 at the approved dose 0.05 mg/kg/day) and 9 who were treated with standard of care.

  • The primary efficacy endpoint was the proportion of patients who achieved a ≥20% reduction from baseline in weekly PN/IV volume at Week 24
  • Secondary endpoints included the change in PN/IV and the number of patients who stopped PN/IV at Week 24

AT 24 WEEKS, 7/10 PATIENTS RESPONDED TO REVESTIVE

  • 69% of children treated with Revestive at the approved dose achieved at least a 20% reduction from baseline in weekly PN/IV volume†6

-vs. 11% with placebo

IN ADDITION, AT WEEK 24 REVESTIVE REDUCED MEAN PN/IV VOLUME§6,7

  • Mean reduction in PN/IV volume of 42% at Week 24‡6

REDUCED THE NUMBER OF DAYS/WEEK ON PN/IV§§6

  • Mean reduction in PN/IV by 1.3 days/week‡6

GAVE COMPLETE FREEDOM FROM PN/IV6

  • As early as Week 24, 3/26 children treated with Revestive were independent from PN/IV‡6
    – vs. 0 with standard of care

IN AN ADDITIONAL 12-WEEK PHASE III STUDY IN CHILDREN WITH SBS-IF, REVESTIVE DELIVERED REDUCTIONS IN PARENTERAL NUTRITION/IV FLUIDS1

At 12 weeks, with Revestive (0.05 mg/kg/day, n=15).1

  • Reduced PN/IV volume by 39% vs. baseline
    – vs. 7% increase with standard of care
  • Reduced the mean number of days/week on PN/IV by 1.36 days
    – vs. no change with standard of care
  • Gave patients an additional 4.18 hours per day free of PN/IV
    – vs. no change with standard of care
  • Gave complete freedom from PN/IV to 3/15 patients

The primary efficacy endpoint was based on clinical response, defined as subject achieving at least 20% reduction in weekly PN/IV volume from baseline (immediately before randomisation) at both weeks 20 and 24. Please note that in the Revestive clinical trials, the mean absolute reduction of PN/IV volume from baseline was significantly higher in the teduglutide group vs placebo at 8 weeks following initiation of treatment. However, individual response may vary as it depends on distinct patient characteristics (eg, remnant bowel anatomy).

** Post-hoc analysis of study completers. Please note that efficacy in this study was based on the intent-to-treat population. Further randomised, controlled clinical trials are necessary to corroborate these findings.

*** Of the 37 Revestive subjects in STEPS, 30 completed 24 months of further treatment with Revestive in STEPS-2 (the Revestive/Revestive group). Of the 39 placebo subjects in STEPS, 29 completed 24 months of treatment with Revestive. At the end of study, 14 (48.3%), 7 (24.1%), and 5 (17.2%) patients achieved a reduction of 1, 2 or 3 days per week in PN/IV, respectively. Two subjects were weaned off their PN/IV while on Revestive. Of the 12 subjects not randomised in the pivotal study, 6 completed 24 months of treatment with Revestive. At the end of study, 3 (50%), 2 (33%), and 2 (33%) achieved a reduction of 1, 2, or 3 days per week in PN/IV, respectively. Two subjects were weaned off their PN/IV while on Revestive.

† All patients were unable to reduce their PN/IV dependence for at least 3 months prior to study entry; weight normalised reduction.

‡ Patients treated with Revestive 0.05 mg/kg/day.

§ All patients were unable to reduce their dependence on PN/IV for at least 3 months prior to the study. Standard deviation for Revestive: -1.3±2. 6.6 days/week baseline PN/IV requirement for Revestive study population, 6.6 days/week baseline PN/IV requirement for SOC study population.

§§ All patients were unable to reduce their dependence on PN/IV for at least 3 months prior to the study. Standard deviation for Revestive: -41.6±28.90; SOC: -10.2±13.59.

PN/IV= parenteral nutrition/intravenous fluids; SBS-IF= short bowel syndrome – intestinal failure 


References

  1. Revestive (teduglutide) Summary of Product Characteristics. Shire Pharmaceuticals Ireland Limited, Dublin, Ireland. November 2017.
  2. Jeppesen PB, Pertkiewicz M, Messing B, et al. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012;143:1473-1481.
  3. Schwartz LK, O’Keefe SJD, Fujioka K, et al. Long-term safety and efficacy of teduglutide for the treatment of intestinal failure associated with short bowel syndrome. Clin Transl Gastroenterol. 2016;7:e142.
  4. O’Keefe SJ, Jeppesen PB, Gilroy R, et al. Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel intestinal failure. Clin Gastroenterol Hepatol. 2013;11:815-823.
  5. Jeppesen PB, Gilroy R, Pertkiewicz M, et al. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011;60:902-914.
  6. Kocoshis SA, Merritt RJ, Hill S, et al. Safety and Efficacy of Teduglutide in Pediatric patients With Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study. JPEN J Parenter Enteral Nutr. 2019. Epub ahead of print.
  7. Hofstetter S. Key issues in addressing the clinical and humanistic burden of short bowel syndrome in the US. Curr Med Res Opin. 2013;29:495-504.
  8. Mullady D, O’Keefe SJD. Treatment of intestinal failure: home parenteral nutrition. Nat Clin Pract Gastroenterol Hepatol. 2006;3:492-504.
  9. Winkler MF. Quality of life in adult home parenteral nutrition patients. JPEN J Parenter Enteral Nutr. 2005;29:162-170.
 
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