Why Prescribe Entyvio?

Proven Efficacy in Clinical Trials

The safety and efficacy of Entyvio is 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=149* 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 <0.0001 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: Patients using oral corticosteroids at baseline who had discontinued corticosteroids beginning at Week 6 and were in clinical remission at Week 52. Patient numbers were n=72 for placebo, n=70 for vedolizumab every eight weeks, and n=73 for vedolizumab every four weeks

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 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: Patients using oral Corticosteroids at baseline who had discontinued Corticosteroids beginning at Week 6 and were in clinical remission at Week 52. Patients numbers were n=82 for placebo, n=82 for vedolizumab every eight weeks, and n=80 for vedolizumab every four weeks
  • 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, 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.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 Study (p=0.433)4
Clinical remission, Week 6 Placebo Vedolizumab
Overall 12.1% (n=207) 19.1% (n=209)
TNFα Antagonist(s) Failure 12.1% (n=157) 15.2%§ (n=158)
TNFα Antagonist(s) Naïve 12.0% (n=50) 31.4% (n=51)
Clinical remission, Week 10
Overall 13.0% (n=207) 28.7% (n=209)
TNFα Antagonist(s) Failure¶,‡ 12.1% (n=157) 26.6% (n=158)
TNFα Antagonist(s) Naïve 16.0% (n=50) 35.3% (n=51)
Sustained clinical remission#
Overall 8.2% (n=207) 15.3% (n=209)
TNFα Antagonist(s) Failure¶,‡ 8.3% (n=157) 12.0% (n=158)
TNFα Antagonist(s) Naïve 8.0% (n=50) 25.5% (n=51)
Enhanced clinical response, Week 6
Overall^ 22.7% (n=207) 39.2% (n=209)
TNFα Antagonist(s) Failure 22.3% (n=157) 39.2% (n=158)
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
  • n=157 for placebo and n=158 for vedolizumab
  • #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.5

Estimated enrollment 2,200. Expected completion 2016.

  • Ongoing
  • Open-label
  • Long-term safety
  • Patients with UC or CD

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=149* 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 <0.0001 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: Patients using oral corticosteroids at baseline who had discontinued corticosteroids beginning at Week 6 and were in clinical remission at Week 52. Patient numbers were n=72 for placebo, n=70 for vedolizumab every eight weeks, and n=73 for vedolizumab every four weeks

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.

BACK TO TOP

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 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: Patients using oral Corticosteroids at baseline who had discontinued Corticosteroids beginning at Week 6 and were in clinical remission at Week 52. Patients numbers were n=82 for placebo, n=82 for vedolizumab every eight weeks, and n=80 for vedolizumab every four weeks
  • Durable clinical remission: Clinical remission at ≥80% of study visits including final visit (Week 52)

Design

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

BACK TO TOP

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, 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.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 Study (p=0.433)4
Clinical remission, Week 6 Placebo Vedolizumab
Overall 12.1% (n=207) 19.1% (n=209)
TNFα Antagonist(s) Failure 12.1% (n=157) 15.2%§ (n=158)
TNFα Antagonist(s) Naïve 12.0% (n=50) 31.4% (n=51)
Clinical remission, Week 10
Overall 13.0% (n=207) 28.7% (n=209)
TNFα Antagonist(s) Failure¶,‡ 12.1% (n=157) 26.6% (n=158)
TNFα Antagonist(s) Naïve 16.0% (n=50) 35.3% (n=51)
Sustained clinical remission#
Overall 8.2% (n=207) 15.3% (n=209)
TNFα Antagonist(s) Failure¶,‡ 8.3% (n=157) 12.0% (n=158)
TNFα Antagonist(s) Naïve 8.0% (n=50) 25.5% (n=51)
Enhanced clinical response, Week 6
Overall^ 22.7% (n=207) 39.2% (n=209)
TNFα Antagonist(s) Failure 22.3% (n=157) 39.2% (n=158)
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
  • n=157 for placebo and n=158 for vedolizumab
  • #Sustained clinical remission: clinical remission at Week 6 and 10
  • ^Exploratory endpoint
  • Enhanced clinical response: CDAI-100 response at Week 6
  • Ongoing
  • Open-label
  • Long-term safety
  • Patients with UC or CD

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

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.

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. Any adverse events observed following the prescription of Entyvio should be reported. In the United Kingdom, adverse event reporting forms and information can be found at https://yellowcard.mhra.gov.uk/.

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