Why Prescribe Entyvio?

Proven Efficacy in Clinical Trials

The safety and efficacy of Entyvio are supported by the results of the GEMINI Studies.1-5

These phase III studies involved more than 2,400 individuals with ulcerative colitis (UC) or Crohn’s disease (CD) who were recruited from nearly 40 countries. GEMINI is the largest phase III clinical trial programme to date that evaluated a new treatment for UC or CD concurrently.

The pivotal trials that led to marketing authorisation being granted were GEMINI I in UC1,2 and GEMINI II & III in CD.1,3

Ulcerative Colitis

GEMINI I.2
 

895, moderately to severely active UC despite treatment with at least one conventional therapy or an anti-TNFα biologic.

Design

Two-phase, multicentre, Phase III, randomised, blinded, placebo-controlled study:

  • Induction phase to establish efficacy and safety for the induction of clinical response and remission
  • Maintenance phase to establish efficacy and safety for the maintenance of clinical response and remission in patients who showed a clinical response at Week 6 (defined as a reduction in the Mayo Clinic score of at least 3 points and a decrease of at least 30% from the baseline score, with a decrease of at least 1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1)

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Treatment

Vedolizumab 300 mg or placebo i.v. infusions at Weeks 0, 2, 6 and then at 4-week intervals, or 8-week intervals for up to 1 year.

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Outcome Measures

Primary Endpoints

Induction Phase:

Maintenance Phase:

Secondary Endpoints

Induction Phase

Maintenance Phase

  • Durable clinical response (response at both Weeks 6 and 52)
  • Durable clinical remission (remission at both Weeks 6 and 52)
  • Mucosal healing at Week 52
  • Steroid remission at Week 52 (if received at baseline)
  • Health-related quality of life
  • Adverse events

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Results

Week 6 Efficacy Results of GEMINI I1
Placebo Vedolizumab
Endpoint n=149 n=225
Clinical Response¶1 26% 47%*
Clinical Remission§ 5% 17%
Mucosal Healing¶2 25% 41%
* p<0.001
p=0.001
p=0.001
§ Clinical Remission: Mayo Clinic score of ≤2 points and no individual subscore >1 point
¶1 Clinical Response: Reduction to the Mayo Clinic score of at least 3 points and a decrease of at least 30% from the baseline score, with a decrease of at least 1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1.
¶2 Mucosal Healing: Mayo Clinic scale endoscopic subscore of ≤1 point
Week 52 Efficacy Results of GEMINI I1
Placebo Vedolizumab Every 8 Weeks Vedolizumab Every 4 Weeks
Endpoint n=126* n=122 n=125
Clinical Remission 16% 42% 45%
Durable Clinical Response 24% 57% 52%
Durable Clinical Remission# 9% 21%§ 24%
Mucosal Healing 20% 52% 56%
Corticosteroid-free Clinical Remission 14% 31%§ 45%
* The placebo group includes those subjects who received vedolizumab at Week 0 and Week 2, and were randomised to receive placebo from Week 6 through Week 52.
p<0.001 vs placebo
p<0.001 vs placebo
§ p<0.05 vs placebo
Durable clinical response: Clinical response at Weeks 6 and 52
# Durable clinical remission: Clinical remission at Weeks 6 and 52
Corticosteroid-free clinical remission was assessed in patients receiving oral glucocorticoids at baseline

Crohn's Disease

GEMINI II.3
 

1,115, moderately to severely active CD despite treatment with at least one conventional therapy or an anti-TNFα biologic.

Design

Two-phase, multicentre, Phase III, randomised, blinded, placebo-controlled study:

  • Induction phase to establish efficacy and safety for the induction of clinical response and remission
  • Maintenance phase to establish efficacy and safety for the maintenance of clinical response and remission in patients who responded to induction at Week 6 (CDAI reduced by ≥ 70)

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Treatment

Vedolizumab 300 mg or placebo i.v. infusions at Weeks 0, 2, 6 and then at 4-week intervals, or 8-week intervals for up to 1 year.

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Outcome Measures

Primary Endpoints

Induction Phase:

Maintenance Phase:

Secondary Endpoints

Induction Phase

  • Mean change in C-reactive protein levels from baseline to Week 6

Maintenance Phase

  • CDAI-100 response at Week 52
  • Steroid-free remission at Week 52
  • Durable clinical remission (Clinical remission ≥ 80% of study visits including final visit)
  • Adverse events

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Results

Efficacy Results of GEMINI II at Week 6

Efficacy Results of GEMINI II at Week 6 Results

Adapted from Sandborn WJ et al. 2013

Efficacy Results of GEMINI II at Week 521
Placebo Vedolizumab Every 8 Weeks Vedolizumab Every 4 Weeks
n=153* n=154 n=154
Clinical Remission 22% 39% 36%
CDAI-100 Response 30% 44% 46%
Corticosteroid-free clinical remission§ 16% 32% 29%
Durable Clinical Remission 14% 21% 16%
  • *The placebo group includes those subjects who received vedolizumab at Week 0 and Week 2, and were randomised to receive placebo from Week 6 through Week 52.
  • p<0.001 vs placebo
  • p≤0.04 vs placebo
  • §Corticosteroid-free clinical remission was assessed in patients receiving oral glucocorticoids at baseline
  • Durable clinical remission: Clinical remission at ≥80% of study visits including final visit (Week 52)

Crohn's Disease

GEMINI III.4
 

416, moderately to severely active CD despite treatment with at least one conventional therapy or an anti-TNFα biologic.

Design

Multicentre, Phase III, randomised, blinded, placebo-controlled study:

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Treatment

Vedolizumab 300 mg or placebo i.v. infusions at Weeks 0, 2, 6.

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Outcome Measures

Primary Endpoints

  • Proportion of subpopulation patients, who had previously failed TNFα antagonist therapy (~75% of enrolled patients), in clinical remission (CDAI score ≤ 150) at Week 6

Secondary Endpoints

  • Proportion of patients in clinical remission at Week 6 in the overall study population (including an additional ~25% of TNFα antagonist-naive patients)
  • Proportion of patients in clinical remission at Week 10 in overall and TNFα antagonist-failure populations
  • Proportion of patients in clinical remission in overall and TNFα antagonist-failure populations at both Weeks 6 and 10
  • Proportion of patients with an enhanced clinical CDAI-100 response in the overall and TNFα antagonist-failure populations at Week 6
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Results

While the primary endpoint of proportion of patients in clinical remission at Week 6 in the TNFα antagonist failure subpopulation was not met, exploratory analyses show that clinically meaningful results were observed.4

The clinical remission rate at Week 6 for the patients who had failed TNFα antagonists was 15.2% for the vedolizumab-treated patients versus 12.1% for those who received placebo (p=0.433; relative risk, 1.2; 95% CI, 0.7-2.2).4

The enhanced efficacy of Entyvio at Week 10 vs Week 6 in the GEMINI III study provides evidence of a later onset of efficacy of Entyvio in patients with moderately to severely active CD, in particular in those who have previously failed TNFα antagonists.4

GEMINI III Study4
Clinical remission, Week 6 Placebo Vedolizumab
TNFα Antagonist(s) Failure 12.1% (n=157) 15.2%§ (n=158)
Overall 12.1% (n=207) 19.1% (n=209)
TNFα Antagonist(s) Naïve 12.0% (n=50) 31.4% (n=51)
Clinical remission, Week 10
TNFα Antagonist(s) Failure 12.1% (n=157) 26.6% (n=158)
Overall 13.0% (n=207) 28.7% (n=209)
TNFα Antagonist(s) Naïve 16.0% (n=50) 35.3% (n=51)
Sustained clinical remission#
TNFα Antagonist(s) Failure 8.3% (n=157) 12.0% (n=158)
Overall 8.2% (n=207) 15.3% (n=209)
TNFα Antagonist(s) Naïve 8.0% (n=50) 25.5% (n=51)
Enhanced clinical response, Week 6
TNFα Antagonist(s) Failure 22.3% (n=157) 39.2% (n=158)
Overall^ 22.7% (n=207) 39.2% (n=209)
TNFα Antagonist(s) Naïve^ 24.0% (n=50) 39.2% (n=51)
  • Secondary endpoint to be viewed as exploratory by pre-specified statistically testing procedure
  • §Primary endpoint not met, p=0.433
  • #Sustained clinical remission: clinical remission at Week 6 and 10
  • ^Exploratory endpoint
  • Enhanced clinical response: CDAI-100 response at Week 6

Long Term Safety

GEMINI LTS
interim analysis.5

2,830 UC and CD patients, exposed to at least one dose of vedolizumab during six double-blind or open-label trials.

Design

Integrated summary of long-term safety (LTS) data from six trials conducted between May 2009 and June 2013.

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Treatment

Vedolizumab or placebo as one or more doses in at least one of the six trials.

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Endpoint Analysis

Exposure-adjusted incidence rates of adverse events, defined as the number of patients experiencing the event per 100 person-years (PYs) of exposure, in the safety population.

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Interim Results

A total of 2,830 patients had 4,811 PYs of vedolizumab exposure (median exposure range, 1–1977 days):

  • No increased risk of any infection or serious infection was associated with vedolizumab exposure
  • Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients)
  • No cases of progressive multifocal leukoencephalopathy were observed
  • Investigator-defined infusion-related reactions were reported for ≤5% of patients in each study
  • <1% were diagnosed with a malignancy
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Design

Two-phase, multicentre, Phase III, randomised, blinded, placebo-controlled study:

  • Induction phase to establish efficacy and safety for the induction of clinical response and remission
  • Maintenance phase to establish efficacy and safety for the maintenance of clinical response and remission in patients who showed a clinical response at Week 6 (defined as a reduction in the Mayo Clinic score of at least 3 points and a decrease of at least 30% from the baseline score, with a decrease of at least 1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1)

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Treatment

Vedolizumab 300 mg or placebo i.v. infusions at Weeks 0, 2, 6 and then at 4-week intervals, or 8-week intervals for up to 1 year.

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Outcome Measures

Primary Endpoints

Induction Phase:

Maintenance Phase:

Secondary Endpoints

Induction Phase

Maintenance Phase

  • Durable clinical response (response at both Weeks 6 and 52)
  • Durable clinical remission (remission at both Weeks 6 and 52)
  • Mucosal healing at Week 52
  • Steroid remission at Week 52 (if received at baseline)
  • Health-related quality of life
  • Adverse events

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Results

Week 6 Efficacy Results of GEMINI I1
Placebo Vedolizumab
Endpoint n=149 n=225
Clinical Response¶1 26% 47%*
Clinical Remission§ 5% 17%
Mucosal Healing¶2 25% 41%
* p<0.001
p=0.001
p=0.001
§ Clinical Remission: Mayo Clinic score of ≤2 points and no individual subscore >1 point
¶1 Clinical Response: Reduction to the Mayo Clinic score of at least 3 points and a decrease of at least 30% from the baseline score, with a decrease of at least 1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1.
¶2 Mucosal Healing: Mayo Clinic scale endoscopic subscore of ≤1 point
Week 52 Efficacy Results of GEMINI I1
Placebo Vedolizumab Every 8 Weeks Vedolizumab Every 4 Weeks
Endpoint n=126* n=122 n=125
Clinical Remission 16% 42% 45%
Durable Clinical Response 24% 57% 52%
Durable Clinical Remission# 9% 21%§ 24%
Mucosal Healing 20% 52% 56%
Corticosteroid-free Clinical Remission 14% 31%§ 45%
* The placebo group includes those subjects who received vedolizumab at Week 0 and Week 2, and were randomised to receive placebo from Week 6 through Week 52.
p<0.001 vs placebo
p<0.001 vs placebo
§ p<0.05 vs placebo
Durable clinical response: Clinical response at Weeks 6 and 52
# Durable clinical remission: Clinical remission at Weeks 6 and 52
Corticosteroid-free clinical remission was assessed in patients receiving oral glucocorticoids at baseline

Design

Two-phase, multicentre, Phase III, randomised, blinded, placebo-controlled study:

  • Induction phase to establish efficacy and safety for the induction of clinical response and remission
  • Maintenance phase to establish efficacy and safety for the maintenance of clinical response and remission in patients who responded to induction at Week 6 (CDAI reduced by ≥ 70)

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Treatment

Vedolizumab 300 mg or placebo i.v. infusions at Weeks 0, 2, 6 and then at 4-week intervals, or 8-week intervals for up to 1 year.

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Outcome Measures

Primary Endpoints

Induction Phase:

Maintenance Phase:

Secondary Endpoints

Induction Phase

  • Mean change in C-reactive protein levels from baseline to Week 6

Maintenance Phase

  • CDAI-100 response at Week 52
  • Steroid-free remission at Week 52
  • Durable clinical remission (Clinical remission ≥ 80% of study visits including final visit)
  • Adverse events

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Results

Efficacy Results of GEMINI II at Week 6

Efficacy Results of GEMINI II at Week 6 Results

Adapted from Sandborn WJ et al. 2013

Efficacy Results of GEMINI II at Week 521
Placebo Vedolizumab Every 8 Weeks Vedolizumab Every 4 Weeks
n=153* n=154 n=154
Clinical Remission 22% 39% 36%
CDAI-100 Response 30% 44% 46%
Corticosteroid-free clinical remission§ 16% 32% 29%
Durable Clinical Remission 14% 21% 16%
  • *The placebo group includes those subjects who received vedolizumab at Week 0 and Week 2, and were randomised to receive placebo from Week 6 through Week 52.
  • p<0.001 vs placebo
  • p≤0.04 vs placebo
  • §Corticosteroid-free clinical remission was assessed in patients receiving oral glucocorticoids at baseline
  • Durable clinical remission: Clinical remission at ≥80% of study visits including final visit (Week 52)

Design

Multicentre, Phase III, randomised, blinded, placebo-controlled study:

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Treatment

Vedolizumab 300 mg or placebo i.v. infusions at Weeks 0, 2, 6.

BACK TO TOP

Outcome Measures

Primary Endpoints

  • Proportion of subpopulation patients, who had previously failed TNFα antagonist therapy (~75% of enrolled patients), in clinical remission (CDAI score ≤ 150) at Week 6

Secondary Endpoints

  • Proportion of patients in clinical remission at Week 6 in the overall study population (including an additional ~25% of TNFα antagonist-naive patients)
  • Proportion of patients in clinical remission at Week 10 in overall and TNFα antagonist-failure populations
  • Proportion of patients in clinical remission in overall and TNFα antagonist-failure populations at both Weeks 6 and 10
  • Proportion of patients with an enhanced clinical CDAI-100 response in the overall and TNFα antagonist-failure populations at Week 6
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Results

While the primary endpoint of proportion of patients in clinical remission at Week 6 in the TNFα antagonist failure subpopulation was not met, exploratory analyses show that clinically meaningful results were observed.4

The clinical remission rate at Week 6 for the patients who had failed TNFα antagonists was 15.2% for the vedolizumab-treated patients versus 12.1% for those who received placebo (p=0.433; relative risk, 1.2; 95% CI, 0.7-2.2).4

The enhanced efficacy of Entyvio at Week 10 vs Week 6 in the GEMINI III study provides evidence of a later onset of efficacy of Entyvio in patients with moderately to severely active CD, in particular in those who have previously failed TNFα antagonists.4

GEMINI III Study4
Clinical remission, Week 6 Placebo Vedolizumab
TNFα Antagonist(s) Failure 12.1% (n=157) 15.2%§ (n=158)
Overall 12.1% (n=207) 19.1% (n=209)
TNFα Antagonist(s) Naïve 12.0% (n=50) 31.4% (n=51)
Clinical remission, Week 10
TNFα Antagonist(s) Failure 12.1% (n=157) 26.6% (n=158)
Overall 13.0% (n=207) 28.7% (n=209)
TNFα Antagonist(s) Naïve 16.0% (n=50) 35.3% (n=51)
Sustained clinical remission#
TNFα Antagonist(s) Failure 8.3% (n=157) 12.0% (n=158)
Overall 8.2% (n=207) 15.3% (n=209)
TNFα Antagonist(s) Naïve 8.0% (n=50) 25.5% (n=51)
Enhanced clinical response, Week 6
TNFα Antagonist(s) Failure 22.3% (n=157) 39.2% (n=158)
Overall^ 22.7% (n=207) 39.2% (n=209)
TNFα Antagonist(s) Naïve^ 24.0% (n=50) 39.2% (n=51)
  • Secondary endpoint to be viewed as exploratory by pre-specified statistically testing procedure
  • §Primary endpoint not met, p=0.433
  • #Sustained clinical remission: clinical remission at Week 6 and 10
  • ^Exploratory endpoint
  • Enhanced clinical response: CDAI-100 response at Week 6

Design

Integrated summary of long-term safety (LTS) data from six trials conducted between May 2009 and June 2013.

BACK TO TOP

Treatment

Vedolizumab or placebo as one or more doses in at least one of the six trials.

BACK TO TOP

Endpoint Analysis

Exposure-adjusted incidence rates of adverse events, defined as the number of patients experiencing the event per 100 person-years (PYs) of exposure, in the safety population.

BACK TO TOP

Interim Results

A total of 2,830 patients had 4,811 PYs of vedolizumab exposure (median exposure range, 1–1977 days):

  • No increased risk of any infection or serious infection was associated with vedolizumab exposure
  • Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients)
  • No cases of progressive multifocal leukoencephalopathy were observed
  • Investigator-defined infusion-related reactions were reported for ≤5% of patients in each study
  • <1% were diagnosed with a malignancy
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Safety and Tolerability Profile

In the combined studies of GEMINI I, II and III, the adverse reactions that occurred in ≥ 5% were nausea, nasopharyngitis, upper respiratory tract infection, arthralgia, pyrexia, fatigue, headache and cough.1 In a 5-year interim analysis of the GEMINI LTS study investigating the safety implications of Entyvio exposure, there was no increased risk of infection or serious infection vs placebo and the malignancy rate was consistent with that seen in the overall IBD population.5

For a full list of possible adverse effects, contraindications and special warnings and precautions for use, please refer to the Entyvio Summary of Product Characteristics. or visit Prescribing Entyvio.

Adverse events should be reported. In the United Kingdom, reporting forms and information can be found at www.mhra.gov.uk/yellowcard.

Adverse events should also be reported to Takeda on 01628 537900 or e-mail DSO-UK@takeda.com