Vedolizumab

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Vedolizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetIntegrin α4β7
Names
Pronunciationve doe liz' ue mab
Trade namesEntyvio
Clinical data
Drug classMonoclonal antibody
Main usesUlcerative colitis, Crohn's disease[1]
Side effectsJoint pain, fever, anaphylaxis, infections, progressive multifocal leukoencephalopathy[2]
Pregnancy
category
  • AU: B2
  • US: B (No risk in non-human studies)
Routes of
use		Intravenous
Typical dose300 mg[2]
External links
AHFS/Drugs.comMonograph
MedlinePlusa614034
Legal
License data
Legal status
Chemical and physical data
FormulaC6528H10072N1732O2042S42
Molar mass146836.99 g·mol−1

Vedolizumab, sold under the brand name Entyvio, is a medication used to treat moderate to severe ulcerative colitis or Crohn's disease that has not responded to other treatments.[1] It is given by gradual injection into a vein.[1] Resistance to the medication may develop.[2]

Common side effects may include joint pain, nausea, fever, and sinusitis.[2] Other side effects may include anaphylaxis, infections, and progressive multifocal leukoencephalopathy.[2] It is a monoclonal antibody which binds to integrin α4β7 (LPAM-1, lymphocyte Peyer's patch adhesion molecule 1) resulting in decreased inflammation.[2][1]

Vedolizumab was approved for medical use in Europe and the United States in 2014.[2][5] In the United Kingdom it costs the NHS about £2,050 a dose.[1] In the United States this amount costs about 6,700 USD as of 2020 or about 40,400 USD per year.[6] In Canada it is about 21,500 CAD a year as of 2016.[7]

Medical uses

Ulcerative colitis

Vedolizumab has been investigated in one main study in adults.[dubious – discuss] Patients with moderate to severe active disease in whom conventional therapy or TNF-alpha antagonists were ineffective or could not be tolerated received either vedolizumab or placebo. The main measure of effectiveness was the proportion of patients whose symptoms improved after six weeks of treatment. Vedolizumab was shown to be more effective than placebo: 47% (106 out of 225) of patients who received vedolizumab showed an improvement in symptoms, compared with 26% (38 out of 149) of patients who received placebo. The study also showed that vedolizumab maintained the effect up to 52 weeks more effectively than placebo.[9][failed verification] Moreover, vedolizumab treatment was shown to achieve higher percentage of clinical remissions (31.3% vs. 22.5%) in patients with ulcerative colitis in comparison to adalimumab treatment.[10]

Crohn's disease

Pyoderma gangrenosum in a individual affected with Crohn's disease A, Necrolytic ulcer with irregular, violaceous, undermined borders on the left medial foot at initial presentation. B, Residual tender, violaceous erythema and cribriform scarring after 4.5 months of local and systemic treatments

In one main study in adult patients with moderate to severe active Crohn's disease in whom conventional therapy or TNF-alpha antagonists were ineffective or could not be tolerated, vedolizumab was shown to be more effective than placebo: 15% (32 out of 220) of patients receiving vedolizumab showed improved symptoms after 6 weeks of treatment, compared with 7% (10 out of 148) of patients on placebo. The maintenance of the effect up to 52 weeks was more effective with vedolizumab than with placebo.[9]

Checkpoint inhibitor colitis

Main article: Checkpoint inhibitor induced colitis

Vedolizumab may be used to treat steroid refractory checkpoint inhibitor induced colitis, if infliximab is ineffective or contraindicated.[11][12]

Dosage

It is given at a dose of 300 mg with repeat doses at 2 and 6 weeks followed by further doses every 8 weeks.[2]

History

The cell line used to develop vedolizumab was created by physician scientists at the Massachusetts General Hospital in Boston as a result of work executed in Dr. Robert Colvin's lab. This was part of a program to analyze the molecular basis of lymphocyte activation.[13] An antibody was isolated that reacted with long term activated antigen-specific (tetanus toxoid) T-lymphocytes originally isolated from blood lymphocytes. The cell lines were created in Dr. Jim T. Kurnick's lab. Although the antibody did not block primary activation of T-lymphocytes, it appeared late after activation with a number of lymphocytic stimuli, and was named "Act-1" because it was the first activation marker identified by this group of investigators. Dr. Andrew Lazarovits, a postdoctoral fellow in the laboratory, discovered the murine homologue of MLN0002,[14][15] chiefly published the original key papers, and up until the late 1990s, coordinated and led the studies for its development and application for Crohn's disease and ulcerative colitis. Dr. Lynn Baird's group showed the antibody reacted with a single protein band of 63Kd, and Dr. Atul Bhan's group showed that it stained tissue lymphocytes but did not react with non-lymphoid tissues. Although Act-1 had limited efficacy in its ability to prevent kidney rejection in a sub-human primate transplantation model, Dr. Lazarovits continued to investigate the activities of Act-1 when he returned to Canada to become the Director of Transplantation at the University of Western Ontario.[15]

It was later determined that the Act-1 monoclonal antibody reacted with an α4β7 integrin that was subsequently shown to interact with a gut-associated addressin, MadCAM. Early work with Dr Bruce Yacyshyn showed differential expression in inflammatory bowel disease.[16] Dr. Lazarovits isolated the antibody to produce the murine homologue MLN002 which he licensed with the Massachusetts General Hospital to Millennium Pharmaceuticals of Boston for further development.[14] Scientists at LeukoSite realized the potential of this antibody to treat inflammatory bowel disease, and this company was eventually acquired by Millennium which took an exclusive license to the cell line from Massachusetts General Hospital. In vivo proof of concept ultimately led to the decision to humanize the antibody and move it into clinical trials as "Vedolizumab". In addition to its reactivity to gut-associated lymphoid tissues, Act-1 antibody also stains large numbers of lymphocytes in rheumatoid synovium, and has been shown by Dr. A. A. Ansari of Emory University to prevent or delay onset of AIDS in a monkey-model of Simian Immunodeficiency Virus-induced AIDS. Thus, reactivity with this antibody may show widespread applicability in inflammatory processes of diverse etiologies.

Society and culture

Approval

Takeda filed a Marketing Authorization Application (MAA) in the European Union on March 7, 2013[17] and a Biologic License Application (BLA) with the U.S. Food and Drug Administration on June 21, 2013 for both Crohn's disease and ulcerative colitis.[18] On September 4, 2013, vedolizumab was given a Priority Review Status, which functions to expedite potential acceptance to market.[19]

On December 9, 2013, the Gastrointestinal Drugs Advisory Committee (GIDAC) and Drug Safety and Risk Management Advisory Committee (DSaRM) discussed the vedolizumab application for approval for both ulcerative colitis and Crohn's disease.[20] The voting went as follows:

  1. Safety and efficacy data outweigh potential risks 21–0
  2. In favour of UC treatment 21–0
  3. In favour for CD treatment 20–1.[21][22]

Although GIDAC/DSaRM were a non-binding advisory committee, their opinions as field experts represent one of the last steps towards drug acceptance.

On 20 March 2014, the Committee for Medicinal Products for Human Use (CHMP, the committee advising the European Commission) adopted a positive opinion, recommending the granting of a marketing authorization for vedolizumab.[23]

On 20 May 2014, vedolizumab was approved by the FDA for treatment of both moderate-to-severe ulcerative colitis and moderate-to-severe Crohn's disease.[24] On May 27, 2014, it was approved for the treatment of both ulcerative colitis and Crohn's disease in the 28 European Union states as well as Norway, Iceland and Liechtenstein. On April 28, 2015 Health Canada approved Entyvio.[25]

Research

Vedolizumab eventually completed a number of phase 3 clinical trials[26][27] for Crohn's Disease and Ulcerative Colitis (GEMINI I,[28] GEMINI II,[29] and GEMINI III[30]) that demonstrate that vedolizumab is an effective and well tolerated drug.[31][32] The results of the GEMINI 1 and GEMINI 2 randomized, placebo controlled multicenter trials of induction and maintenance therapy in Crohn's disease and ulcerative colitis have been published.[33][34] An additional clinical trial, GEMINI LTS (Long-term Safety), is still being run.[35]

HIV infection

On October 13, 2016, scientists from Emory University and National Institute of Allergy and Infectious Diseases (NIAID) published a paper which claimed that they applied daily ART (antiretroviral therapy) of 90 days followed by simianized (rhesus macaques) anti α4β7 antibody on SIV+ rhesus macaques for 23 weeks. Twenty three months after stopping both ART and anti-α4β7 antibody treatment, the in vivo SIV level still remained undetectable. Therefore, treating HIV+ people with ART and anti-α4β7 simultaneously may be a new therapy that could potentially lead to an HIV infection cure.[36] In mice vedolizumab was not able to prevent or control HIV-infections.[37] Phase 1 clinical trial of that therapy has been initialized by NIAID since May 2016. For each of the participants, they will get vedolizumab infusions every four weeks for 30 weeks. Before the 23rd week of vedolizumab infusions, cART (combination ART) is kept. During the 30 weeks, blood draws are repeated for baseline tests. After the 22-week-cART is stopped, both viral load and CD4 count will be monitored biweekly. If HIV viral load goes high or their CD4 cell counts decrease by too much during when vedolizumab is used alone, cART will be brought back on the participants.[38] The published results from this clinical trial suggest "that blockade of α4β7 may not be an effective strategy for inducing virological remission in HIV-infected individuals after ART interruption" because only one patient showed prolonged virus suppression.[39]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 50. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Vedolizumab Monograph for Professionals". Drugs.com. Archived from the original on 5 July 2018. Retrieved 13 September 2021.
  3. ↑ "Entyvio EPAR". European Medicines Agency (EMA). Archived from the original on 13 October 2020. Retrieved 12 October 2020.
  4. ↑ "Entyvio- vedolizumab injection, powder, lyophilized, for solution". DailyMed. 3 April 2020. Archived from the original on 21 October 2020. Retrieved 12 October 2020.
  5. ↑ "Vedolizumab". Archived from the original on 13 October 2020. Retrieved 13 September 2021.
  6. ↑ "How much does Entyvio cost per month?". Drugs.com. Archived from the original on 6 June 2023. Retrieved 13 September 2021.
  7. ↑ "Entyvio (vedolizumab)" (PDF). December 2016. Archived (PDF) from the original on 18 October 2018. Retrieved 13 September 2021.
  8. ↑ "Archive copy". Archived from the original on 2021-04-24. Retrieved 2021-04-23.{{cite web}}: CS1 maint: archived copy as title (link)
  9. ↑ 9.0 9.1 Summary of the risk management plan (RMP) for Entyvio Archived 2018-03-15 at the Wayback Machine, EMA.
  10. ↑ Sands, Bruce E.; Peyrin-Biroulet, Laurent; Loftus, Edward V.; Danese, Silvio; Colombel, Jean-Frédéric; Törüner, Murat; Jonaitis, Laimas; Abhyankar, Brihad; Chen, Jingjing; Rogers, Raquel; Lirio, Richard A.; Bornstein, Jeffrey D.; Schreiber, Stefan (26 September 2019). "Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis". New England Journal of Medicine. 381 (13): 1215–1226. doi:10.1056/NEJMoa1905725. PMID 31553834.
  11. ↑ Brahmer, Julie R.; Lacchetti, Christina; Schneider, Bryan J.; Atkins, Michael B.; Brassil, Kelly J.; Caterino, Jeffrey M.; Chau, Ian; Ernstoff, Marc S.; Gardner, Jennifer M.; Ginex, Pamela; Hallmeyer, Sigrun; Holter Chakrabarty, Jennifer; Leighl, Natasha B.; Mammen, Jennifer S.; McDermott, David F.; Naing, Aung; Nastoupil, Loretta J.; Phillips, Tanyanika; Porter, Laura D.; Puzanov, Igor; Reichner, Cristina A.; Santomasso, Bianca D.; Seigel, Carole; Spira, Alexander; Suarez-Almazor, Maria E.; Wang, Yinghong; Weber, Jeffrey S.; Wolchok, Jedd D.; Thompson, John A. (10 June 2018). "Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline". Journal of Clinical Oncology. 36 (17): 1714–1768. doi:10.1200/JCO.2017.77.6385. PMC 6481621. PMID 29442540.
  12. ↑ Bellaguarda, Emanuelle; Hanauer, Stephen (February 2020). "Checkpoint Inhibitor–Induced Colitis". The American Journal of Gastroenterology. 115 (2): 202–210. doi:10.14309/ajg.0000000000000497. PMID 31922959.
  13. ↑ Lazarovits, A. I.; Moscicki, R. A.; Kurnick, J. T.; Camerini, D.; Bhan, A. K.; Baird, L. G.; Erikson, M.; Colvin, R. B. (1984-10-01). "Lymphocyte activation antigens. I. A monoclonal antibody, anti-Act I, defines a new late lymphocyte activation antigen". The Journal of Immunology. 133 (4): 1857–1862. ISSN 0022-1767. PMID 6088627. Archived from the original on 2021-04-23. Retrieved 2021-04-23.
  14. ↑ 14.0 14.1 Feagan B, Greenberg G, Wild G, Fedorak R, Pi Paré P, McDonald J, Cohen, A, Bitton A, Baker J, Dubé R, Landau S, Vandervoort M, Parikh A. (2008). "Treatment of Active Crohn's Disease With MLN0002, a Humanized Antibody to the α4β7 Integrin". Clinical Gastroenterology and Hepatology. 6 (12): 1370–77. doi:10.1016/j.cgh.2008.06.007. PMID 18829392. Archived from the original on 2021-08-27. Retrieved 2021-04-23.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ↑ 15.0 15.1 Lazarovits AI, Moscicki RA, Kurnick JT, Camerini D, Bhan AK, Baird LG, Erikson M, Colvin RB (1984). "Lymphocyte activation antigens. I. A monoclonal antibody, anti-Act I, defines a new late lymphocyte activation antigen". J. Immunol. 133 (4): 1857–62. PMID 6088627.
  16. ↑ Yacyshyn BR, Lazarovits A, Tsai V, Matejko K (November 1994). "Crohn's disease, ulcerative colitis, and normal intestinal lymphocytes express integrins in dissimilar patterns". Gastroenterology. 107 (5): 1364–71. doi:10.1016/0016-5085(94)90538-x. PMID 7523224.
  17. ↑ "Takeda Submits Marketing Authorisation Application for Vedolizumab in Moderately to Severely Active Ulcerative Colitis and Crohn's Disease in the European Union". Press Release. Takeda Pharmaceutical Company Limited. 2013-03-08. Archived from the original on 2016-07-11. Retrieved 2021-04-23.
  18. ↑ "Takeda Submits Vedolizumab BLA". Drug Discovery and Development. 2013-06-21. Archived from the original on 2017-10-07. Retrieved 2021-04-23.
  19. ↑ "Takeda's New Investigational Drug Vedolizumab is Granted Priority Review Status by U.S. Food and Drug Administration for Ulcerative Colitis". Press Release. Takeda Pharmaceutical Company Limited. 2013-09-04. Archived from the original on 2017-10-07. Retrieved 2021-04-23.
  20. ↑ "Archive copy". Archived from the original on 2016-03-04. Retrieved 2021-04-23.{{cite web}}: CS1 maint: archived copy as title (link)
  21. ↑ "Archive copy" (PDF). Archived (PDF) from the original on 2013-12-15. Retrieved 2021-04-23.{{cite web}}: CS1 maint: archived copy as title (link)
  22. ↑ "Archive copy". Archived from the original on 2015-05-18. Retrieved 2021-04-23.{{cite web}}: CS1 maint: archived copy as title (link)
  23. ↑ "Archive copy". Archived from the original on 2017-10-06. Retrieved 2022-03-14.{{cite web}}: CS1 maint: archived copy as title (link)
  24. ↑ "Archive copy". Archived from the original on 2017-02-04. Retrieved 2021-04-23.{{cite web}}: CS1 maint: archived copy as title (link)
  25. ↑ "Archive copy". Archived from the original on 2016-10-18. Retrieved 2021-04-23.{{cite web}}: CS1 maint: archived copy as title (link)
  26. ↑ "Vedolizumab". List Results. ClinicalTrials.gov. Archived from the original on 2014-11-04. Retrieved 2021-04-23.
  27. ↑ "Data Published in the New England Journal of Medicine for Vedolizumab, an Investigational New Drug from Takeda for Moderately to Severely Active Ulcerative Colitis and Crohn's Disease". Press Release. Takeda Pharmaceutical Company Limited. 2013-08-23. Archived from the original on 2017-01-28. Retrieved 2021-04-23.
  28. ↑ Clinical trial number NCT00783718 at ClinicalTrials.gov
  29. ↑ Clinical trial number NCT00783692 at ClinicalTrials.gov
  30. ↑ Clinical trial number NCT01224171 at ClinicalTrials.gov
  31. ↑ McLean LP, Shea-Donohue T, Cross RK (September 2012). "Vedolizumab for the treatment of ulcerative colitis and Crohn's disease". Immunotherapy. 4 (9): 883–98. doi:10.2217/imt.12.85. PMC 3557917. PMID 23046232.
  32. ↑ Mosli MH, Feagan BG (March 2013). "Vedolizumab for Crohn's disease". Expert Opin Biol Ther. 13 (3): 455–63. doi:10.1517/14712598.2013.770835. PMID 23394379. S2CID 28088195.
  33. ↑ Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A (August 2013). "Vedolizumab as induction and maintenance therapy for ulcerative colitis". N. Engl. J. Med. 369 (8): 699–710. doi:10.1056/NEJMoa1215734. PMID 23964932. S2CID 44955150.
  34. ↑ Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A (August 2013). "Vedolizumab as induction and maintenance therapy for Crohn's disease" (PDF). N. Engl. J. Med. 369 (8): 711–21. doi:10.1056/NEJMoa1215739. PMID 23964933. Archived (PDF) from the original on 2020-06-09. Retrieved 2021-04-23.
  35. ↑ Clinical trial number NCT00790933 at ClinicalTrials.gov
  36. ↑ Byrareddy SN, Arthos J, Cicala C, Villinger F, Ortiz KT, Little D, et al. (October 2016). "Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy". Science. 354 (6309): 197–202. Bibcode:2016Sci...354..197B. doi:10.1126/science.aag1276. PMC 5405455. PMID 27738167. Archived from the original on 2020-11-08. Retrieved 2021-04-23.
  37. ↑ Ling L, Wu T, To KK, Cheung KW, Lui KO, Niu M, et al. (March 2019). "Vedolizumab-mediated integrin α4β7 blockade does not control HIV-1SF162 rebound after combination antiretroviral therapy interruption in humanized mice". AIDS. 33 (4): F1–F12. doi:10.1097/QAD.0000000000002149. PMID 30829743. S2CID 73491150.
  38. ↑ "Vedolizumab (Anti-α4β7) in Subjects With HIV Infection Undergoing Analytical Treatment Interruption". Archived from the original on 2021-04-10. Retrieved 2021-04-23.
  39. ↑ Sneller MC, Clarridge KE, Seamon C, Shi V, Zorawski MD, Justement JS, et al. (September 2019). "7 monoclonal antibody vedolizumab in HIV-infected individuals". Science Translational Medicine. 11 (509). doi:10.1126/scitranslmed.aax3447. PMID 31488581. S2CID 201845576.

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