For U.S. Healthcare Professionals

Safety
Data

For the
long term

For adult patients with moderately to severely active UC or CD when other therapies have not worked well enough or cannot be tolerated.

LONG‑TERM SAFETY PROFILE

2014

Entyvio vs. Placebo

Clinical trials evaluated safety in more than 3300 adults (UC, CD, and healthy volunteers)¹

2017

5-Year Open Label

5-year analysis, which included an open-label continuation study (UC and CD), has demonstrated consistent results across safety parameters²

2019

Safety Data from the Head-to-Head VARSITY Trial

Study was not designed to assess safety differences

2020

Now Up to 7 Years of Consistent Safety Data

A single arm, open-label, multinational study evaluated the long-term safety profile of Entyvio in moderately to severely active UC or CD patients.³

The study evaluated 2243 patients who received Entyvio with a median exposure of 1072 days (range 1 to 3412 days)^3-5

Entyvio demonstrated up to 7 years of consistent results across safety parameters^3-5

UC TRIALS I & II AND CD TRIALS I & III
SELECT ADVERSE EVENTS¹

Entyvio® vs placebo select adverse events for UC Trials I and II and CD Trials I and III.

ADVERSE EVENTS BASED ON UC TRIALS I AND II, CD TRIALS I AND III¹

INFECTIONS

Infection rates with Entyvio were 0.85 per patient-year vs. 0.7 for placebo

Infections consisted primarily of nasopharyngitis, upper respiratory tract infection, sinusitis, and urinary tract infection
2% of patients discontinued Entyvio due to infections

SERIOUS INFECTIONS

Serious infection rates with Entyvio were 0.07 per patient-year vs. 0.06 for placebo

Serious infections included anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis

IMMUNOGENICITY

The rate of detectable anti-vedolizumab antibodies at any time during the 52 weeks of continuous treatment with Entyvio was 6% (86 of 1427 patients)

20 of 86 patients were persistently positive (at 2 or more study visits) for anti-vedolizumab antibody, and 56 of 86 patients developed neutralizing antibodies to vedolizumab
Among these 20 patients, 14 had undetectable or reduced vedolizumab serum concentrations. Five of the 20 patients with persistently positive anti-vedolizumab antibody achieved clinical remission at Week 52 in the controlled trials
Overall, there was no apparent correlation of anti-vedolizumab antibody development to adverse reactions following intravenous administration of Entyvio

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

Although unlikely, a risk of PML cannot be ruled out:

PML, a rare and often fatal opportunistic infection of the central nervous system (CNS), has been reported with systemic immunosuppressants, including another integrin receptor antagonist. PML is caused by the John Cunningham (JC) virus and typically only occurs in patients who are immunocompromised
1 case of PML in an Entyvio-treated patient with multiple contributory factors has been reported in the postmarketing setting (e.g., human immunodeficiency virus [HIV] infection with a CD4 count of 300 cells/mm³ and prior and concomitant immunosuppression)

LIVER INJURY

Entyvio should be discontinued in patients with jaundice or other evidence of significant liver injury
3 patients reported serious adverse reactions of hepatitis with Entyvio; 1 additional case of serious hepatitis was seen in the open-label trial

These adverse reactions occurred following 2 to 5 Entyvio doses; however, it is unclear if the reactions indicated drug-induced or autoimmune etiology
There have been reports of elevations of transaminase and/or bilirubin in patients receiving Entyvio
All patients recovered following discontinuation of therapy with or without treatment with corticosteroids

MALIGNANCIES

Malignancies (excluding dysplasia and basal cell carcinoma) were in 0.4% (6 of 1434) of patients treated with Entyvio and in 0.3% (1 of 297) of patients treated with placebo

The number of malignancies in clinical trials was small; however, long-term exposure was limited

ADVERSE REACTIONS

Adverse reactions were reported in 52% of patients treated with Entyvio (N=1434) and 45% of patients treated with placebo (N=297)

Over 52 weeks, 7% of patients treated with Entyvio experienced serious adverse reactions compared to 4% treated with placebo

INFUSION‑RELATED REACTIONS (IRRS) AND HYPERSENSITIVITY REACTIONS

4% of patients treated with Entyvio (N=1434) experienced an IRR vs 3% of patients on placebo (N=297)
1 case of anaphylaxis (1 of 1434 patients treated with Entyvio) was reported by a CD patient during the second infusion (symptoms reported were dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate) and was managed with discontinuation of infusion and treatment with antihistamine and IV hydrocortisone
Most frequently observed IRRs in patients treated with Entyvio were nausea, headache, pruritus, dizziness, fatigue, infusion-related reaction, pyrexia, urticaria, and vomiting. These reactions generally occurred within the first two hours after the infusion and resolved with no treatment or following antihistamine and/or IV hydrocortisone treatment

NOW UP TO 7 YEARS OF CONSISTENT SAFETY DATA IN UC AND CD^3-5

STUDY DESIGN/METHODOLOGY

GEMINI LTS was a phase 3, single-arm, open-label, multinational study evaluating the long-term safety profile of Entyvio in patients with moderately to severely active UC or CD

Patients were enrolled from the phase 3 studies GEMINI 1, GEMINI 2, GEMINI 3, a long-term phase 2 study, and included a cohort of Entyvio-naive patients with UC and CD. Data were collected from May 2009 to October 2017
The study evaluated 2243 UC and CD patients who received Entyvio with a median exposure of 42.4 months for UC (range 0.03 to 112.2 months) and 31.5 months for CD (range 0.03 to 100.3 months)
The safety population included all patients who received any dose of Entyvio

BASELINE CHARACTERISTICS

MEDIAN ENTYVIO EXPOSURE IN UC: 42.4 MONTHS, RANGE 0.03–112.2 MONTHS

MEDIAN ENTYVIO EXPOSURE IN CD: 31.5 MONTHS, RANGE 0.03–100.3 MONTHS

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LTS = long-term safety.

Exposure-adjusted incidence rates
of any AE or SAE

Entyvio® adverse event rates. — Number of patients with
event/1000 PYs of exposure*

* Time-adjusted incidence rate per 1000 PYs = (number of patients experiencing an AE of interest/total person time in years) x 1000.

Open-label study up to 7 years demonstrated a consistent safety profile in UC and CD patients

The most frequent AEs were disease exacerbations (35.9% UC, 35.3% CD), nasopharyngitis (28.2% UC, 25.4% CD) and arthralgia (17.3% UC, 24.4% CD)
39.7% of AEs in UC and 46.2% of AEs in CD were considered by the treating physician to be related to exposure to Entyvio

NO NEW SIGNALS OF:

Infections
Malignancies
Infusion-related reactions
Hepatic injury

Exposure-adjusted incidence rates of selected AEs

Number of patients with event/1000 PYs of exposure*

Incidence rates of selected adverse events with Entyvio®.

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* Time-adjusted incidence rate per 1000 PYs = (number of patients experiencing an AE of interest/total person time in years) x 1000.

^† Although unlikely, a risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms.¹

No new safety signals up to 7 years in UC and CD patients

GEMINI LTS identified no cases of PML with 7999 PYs of Entyvio exposure^†

AE = adverse event; LTS = long-term safety; PML = progressive multifocal leukoencephalopathy; PY = patient year; SAE = serious adverse event.

ADVERSE EVENTS OBSERVED IN THE VARSITY STUDY

Safety Was Evaluated in 383 Patients: No New Safety Signals Were Observed for Entyvio^6-8

STUDY WAS NOT DESIGNED TO ASSESS SAFETY DIFFERENCES

ADVERSE EVENTS IN SAFETY POPULATION

The most frequent AEs* for adalimumab and Entyvio were as follows: ≥1 TEAE, 35.8% and 32.9%; ulcerative colitis, 16.3% and 11.5%; nasopharyngitis, 7.8% and 7.0%; headache, 5.4% and 7.0%; anemia, 6.7% and 5.2%; abdominal pain, 5.2% and 4.7%; upper respiratory tract infection, 4.4% and 5.2%

* Adverse events that occurred during the trial period. Trial period was the time from the first dose of a trial drug and up to 126 days after the last dose.

^† Adverse events were classified according to the Medical Dictionary for Regulatory Activities System Organ Class categorization and preferred terms (version 21.0). The safety population was defined as all patients who received at least one dose of the study drug.

^‡ No cases of progressive multifocal leukoencephalopathy.

^§ Not related to Entyvio.

^‖ Updated to include final 68-week safety follow-up.

AE = adverse event; TEAE = treatment-emergent adverse event.

See the VARSITY study results

Crohn's Disease Data

SEE RESULTS IN CD

Dosing & Administration

REVIEW THE GUIDANCE

Important Safety Information

ENTYVIO (vedolizumab) for injection is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients.
Infusion-related reactions and hypersensitivity reactions including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate have been reported. These reactions may occur with the first or subsequent infusions and may vary in their time of onset from during infusion or up to several hours post-infusion. If anaphylaxis or other serious infusion-related or hypersensitivity reactions occur, discontinue administration of ENTYVIO immediately and initiate appropriate treatment.
Patients treated with ENTYVIO are at increased risk for developing infections. Serious infections have been reported in patients treated with ENTYVIO, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis. ENTYVIO is not recommended in patients with active, severe infections until the infections are controlled. Consider withholding ENTYVIO in patients who develop a severe infection while on treatment with ENTYVIO. Exercise caution in patients with a history of recurring severe infections. Consider screening for tuberculosis (TB) according to the local practice.
Progressive multifocal leukoencephalopathy (PML), a rare and often fatal opportunistic infection of the central nervous system (CNS), has been reported with systemic immunosuppressants, including another integrin receptor antagonist. PML is caused by the John Cunningham (JC) virus and typically only occurs in patients who are immunocompromised. One case of PML in an ENTYVIO-treated patient with multiple contributory factors has been reported in the postmarketing setting (e.g., human immunodeficiency virus [HIV] infection with a CD4 count of 300 cells/mm³ and prior and concomitant immunosuppression). Although unlikely, a risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. If PML is suspected, withhold dosing with ENTYVIO and refer to a neurologist; if confirmed, discontinue ENTYVIO dosing permanently.
There have been reports of elevations of transaminase and/or bilirubin in patients receiving ENTYVIO. ENTYVIO should be discontinued in patients with jaundice or other evidence of significant liver injury.
Prior to initiating treatment with ENTYVIO, all patients should be brought up to date with all immunizations according to current immunization guidelines. Patients receiving ENTYVIO may receive non-live vaccines and may receive live vaccines if the benefits outweigh the risks.
Most common adverse reactions (incidence ≥3% and ≥1% higher than placebo): nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities.

Please see full Prescribing Information, including Medication Guide.

Indications

Adult Ulcerative Colitis (UC)

ENTYVIO (vedolizumab) is indicated in adults for the treatment of moderately to severely active UC.

Adult Crohn's Disease (CD)

ENTYVIO (vedolizumab) is indicated in adults for the treatment of moderately to severely active CD.

ENTYVIO is available for injection: 300 mg vedolizumab.

Please see full Prescribing Information, including Medication Guide.

References:

Entyvio (vedolizumab) prescribing information. Takeda Pharmaceuticals.
Colombel JF, Sands BE, Rutgeerts P, et al. Gut. 2017;66(5):839-851.
Loftus EV, Feagan BG, Panaccione R, et al; for the GEMINI LTS study team. Aliment Pharmacol Ther. 2020;00:1-13.
Data on file. MLN0002, Final CSR C13008, July 2018. Takeda Pharmaceuticals USA, Inc.
Data on file. Internal communication, October 2020. Takeda Pharmaceuticals USA, Inc.
Data on file. Internal communication, November 2019. Takeda Pharmaceuticals USA, Inc.
Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. N Engl J Med. 2019;381(13):1215-1226.
Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. N Engl J Med. 2019;381(13):1215-1226. (supplemental appendix).

Safety Data

For the long term