Avelumab

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Avelumab
Mass / length primary structure 147 kDa
Identifier
External IDs
Drug information
ATC code L01X-C
Drug class Monoclonal antibody

Avelumab (brand name Bavencio ) is a fully human monoclonal antibody from the class of immune checkpoint inhibitors . It is being developed for use in cancer immunotherapy . Avelumab binds specifically to the programmed cell death ligand 1 ( PD-L1 ). Avelumab received the Orphan Drug Designation (ODD) for the treatment of Merkel cell carcinoma in December 2015 and for the treatment of gastric cancer from the European Commission in December 2016. The plasma half-life is 6.1 days. Avelumab was developed by Merck KGaA . The company generated sales of € 69 million with Bavencio in 2018 . In the previous year, sales of this drug were € 21 million.

pharmacology

Assumed mechanism of action

Avelumab is a human IgG1 monoclonal antibody. It binds to the programmed cell death ligand 1 (PD-L1) and it is assumed that it prevents it from binding to its receptor PD-1. A PD-1 / PD-L1 receptor / ligand interaction leads to the inhibition of CD8 + T cells and thus to the inhibition of an immune defense.

Immunotherapy aims to remove this inhibition by preventing the interaction between receptor and ligand. Avelumab is believed to inhibit the PD-1 / PD-L1 interaction, which in turn increases the CD8 + T-cell immune response.

In addition, avelumab was developed in such a way that antibody dependent cellular cytotoxicity (ADCC) may also contribute to the mode of action of avelumab. Avelumab was able to show this mechanism of action in vitro .

In addition to PD-L1, PD-1 is also a target for immunotherapy. Avelumab belongs to a group of immunotherapeutic agents.

Clinical studies

Avelumab has been investigated in phase I, phase II and phase III studies in various indications since May 2015. The Phase III JAVELIN Ovarian PARP 100 study in untreated advanced ovarian cancer was discontinued in March 2019.

In February 2018, the phase III JAVELIN Lung 200 study with the indication of bronchial carcinoma failed to meet the primary endpoint. The overall survival rate could not be improved. In November 2017, the Phase III trial failed JAVELIN Gastric 300 for third-line treatment of patients with inoperable, recurrent or metastatic adenocarcinoma of the stomach for the same reason.

Approvals and areas of application

The US Food and Drug Administration FDA has Avelumab for treatment for two indications in the way of the so-called. Accelerated approvals approved . On March 23, 2017, the FDA initially approved accelerated approval of avelumab for the treatment of adults and children (12 years of age and older) with metastatic Merkel cell carcinoma (MCC). The Merkel cell carcinoma is a very rare form of skin cancer. In May 2017, the accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC), whose tumor disease progressed with or after platinum-containing chemotherapy or whose tumor disease had progressed within 12 months after neoadjuvant or adjuvant treatment with platinum-containing chemotherapy (e B. with cisplatin , carboplatin or oxaliplatin ). Both indications were approved using the accelerated procedure based on response and response time. Continuing approval for these indications can be made dependent on the verification and description of the clinical benefit in confirmatory studies. At the end of September 2017, the drug received approval for the EU ; the market launch is scheduled for October 2017.

Individual evidence

  1. ↑ a b Highlights of Prescribing Information fda.gov
  2. ↑ 1537032-82-8 commonchemistry.org
  3. ^ A b Esther S. Kim: Avelumab: First Global Approval . In: Drugs . tape 77 , no. 8 , May 2017, p. 929-937 , doi : 10.1007 / s40265-017-0749-6 .
  4. ↑ European Medicines Agency: Public summary of opinion on orphan designation. Retrieved August 24, 2017 .
  5. ↑ European Medicines Agency: Public summary of opinion on orphan designation: Avelumab for the treatment of gastric cancer. Retrieved January 9, 2017 .
  6. ↑ Merck Achieves 2018 Targets and Is Set for Profitable Growth. Press release of March 7, 2019
  7. ↑ BAVENCIO - Full Prescribing Information. Retrieved August 24, 2017 .
  8. ↑ Omid Hamid, Caroline Robert, Adil Daud, F. Stephen Hodi, Wen-Jen Hwu: Safety and Tumor Responses with Lambrolizumab (Anti-PD-1) in Melanoma . In: The New England journal of medicine . tape 369 , no. 2 , July 11, 2013, p. 134-144 , doi : 10.1056 / NEJMoa1305133 , PMID 23724846 , PMC 4126516 (free full text).
  9. ↑ clinicaltrials.gov
  10. ↑ Merck and Pfizer discontinue phase III study. In: finanzen.net. March 20, 2019, accessed May 11, 2019 .
  11. ↑ Dpa-Afx / Daz.online: Merck suffers another setback with avelumab. In: deutsche-apotheker-zeitung.de. February 15, 2018, accessed May 11, 2019 .
  12. ↑ Julia Borsch: Avelumab does not reach the endpoint. In: deutsche-apotheker-zeitung.de. November 29, 2017. Retrieved May 11, 2019 .
  13. ^ Pfizer, Merck KGaA fourth to market with PD-1 / L1 inhibitor . In: BioPharma Dive . ( biopharmadive.com [accessed September 1, 2017]).
  14. ↑ American Cancer Society: Merkel Cell Skin Cancer. Retrieved August 24, 2017 .
  15. ^ Center for Drug Evaluation and Research: Approved Drugs - FDA grants accelerated approval to avelumab for urothelial carcinoma. Retrieved September 1, 2017 (English).
  16. ↑ EU approval for Bavencio. In: apotheke-adhoc.de. September 21, 2017. Retrieved September 27, 2017 .
  17. ↑ Darmstadt: Merck receives EU approval for cancer carrier Bavencio. In: Mannheimer Morgen . September 21, 2017. Retrieved September 27, 2017 .