PARP inhibitor

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PARP inhibitors are a relatively new, still small group of drugs that are used to treat various cancers (e.g. ovarian cancer ). PARP inhibitors are inhibitors of the enzyme P oly- A DP R ibose- P Polymerase (PARP) and prevent cancer cells through a cytostatic drugs induced DNA damage repair. PARP inhibitors are therefore primarily an option as maintenance therapy after chemotherapy .

First representative

  • Olaparib (trade name: Lynparza , manufacturer: AstraZeneca ) was the first active ingredient to be approved in the USA in 2015 . Lynparza may be used as monotherapy for maintenance therapy in adult patients with platinum-sensitive recurrence of a BRCA-mutated, highly serous epithelial ovarian, fallopian tube or peritoneal carcinoma. Before starting treatment, a mutation in the BRCA1 or BRCA2 genes must be detected in the blood or tumor tissue . Olaparib is also approved in the EU. In December 2017, initial data on the treatment of HER2-negative metastatic breast cancer were presented at the San Antonio Breast Cancer Symposium (SABCS) . Merck (MSD) and AstraZeneca Collaborate in Clinical Development of Olaparib. In January 2018 the US Food and Drug Administration expanded the indication area for olaparib to include metastatic breast cancer with a specific genetic mutation (BRCA mutation). In June 2018, the Drugs Commission of the German Medical Association (AkdÄ) published a report on olaparib due to the risk of medication errors in a new dosage form in a Rote-Hand-Brief , according to which capsules and tablets containing olaparib are neither 1: 1 due to the different dosage and bioavailability may still be exchanged on a milligram basis.
  • In March 2017, the FDA approved niraparib (trade name: Zejula , manufacturer: Tesaro ), another PARP inhibitor for the treatment of ovarian cancer and related malignancies. The European Commission (EC) approved Zejula (niraparib) in the European Union EU in November 2017 . Zejula is the first oral, once-daily PARP inhibitor approved in Europe that does not require testing for BRCA mutation status or other biomarker testing .
  • Another representative is rucaparib (trade name: Rubraca , manufacturer: Clovis Oncology ), also approved for the treatment of ovarian cancer in the USA in December 2016. Rucararib may also only be used in patients who have mutations in BRCA genes. These genes are involved in DNA repair and their failure increases the effectiveness of PARP inhibitors. In October 2012, rucaparib received the Orphan Drug Designation (ODD) for the treatment of ovarian cancer in the EU . In May 2018, the EU Commission approved rucaparib - as an orphan drug - for the oral treatment of adult patients with platinum-sensitive, relapsed or progressive, high-grade epithelial ovarian, fallopian tube or peritoneal carcinoma with BRCA mutations (germline and / or somatic) who have been treated with two or more previous platinum-based chemotherapy lines and are not eligible for further platinum-based chemotherapy.

Candidates

Other companies are also working on other PARP inhibitors, e.g. B. AbbVie to Veliparib and Sanofi to Iniparib (research already stopped).

literature

Individual evidence

  1. ↑ Lynparza Approval History , approval history on drugs.com, accessed on September 19, 2017.
  2. ↑ FDA approves olaparib tablets for maintenance treatment in ovarian cancer , PM FDA dated August 17, 2017, accessed September 19, 2017.
  3. ↑ NEUE ARZNEISTOFFE , Pharmazeutische Zeitung, accessed on September 19, 2017.
  4. ↑ Overview of Lynparza and rationale for approval in the EU , EMA from April 2018, accessed on June 18, 2018.
  5. ↑ New and Updated Data for Merck's KEYTRUDA® (pembrolizumab) and Updated Data on LYNPARZA® (olaparib) in Multiple Breast Cancer Subtypes to Be Presented at the 2017 San Antonio Breast Cancer Symposium (SABCS) , PM Merck / MSD of November 30, 2017 , accessed December 6, 2017.
  6. ↑ FDA approves first treatment for breast cancer with a certain inherited genetic mutation , PM FDA of January 12, 2018, accessed on January 18, 2018.
  7. ↑ Risk of medication errors due to a new dosage form , Rote-Hand-Brief on olaparib from the marketing authorization holder AstraZeneca dated June 15, 2018, accessed on June 18, 2018.
  8. ↑ Niraparib (ZEJULA) , PM FDA of March 27, 2017, accessed November 27, 2017.
  9. ↑ TESARO ANNOUNCES US FDA APPROVAL OF ZEJULA ™ (NIRAPARIB) FOR WOMEN WITH RECURRENT OVARIAN CANCER ( Memento of September 22, 2017 in the Internet Archive ) PM TESARO of March 27, 2017, accessed on September 19, 2017.
  10. ↑ TESARO Announces European Commission Approval of ZEJULA® for Women With Recurrent Ovarian Cancer ( Memento from December 1, 2017 in the Internet Archive ), PM TESARO from November 20, 2017, accessed on November 27, 2017.
  11. ↑ Rucaparib , PM FDA dated December 19, 2016, accessed September 19, 2017.
  12. ↑ Orphan Designation for Rucaparib , EMA, accessed September 19, 2017.
  13. ↑ SUMMARY OF THE CHARACTERISTICS OF THE EMA'S EPAR MEDICINAL PRODUCT , accessed June 6, 2018