Rucaparib, sold under the brand name Rubraca, is a

PARP inhibitor PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). They are developed for multiple indications, including the treatment of heritable cancers. Several forms of cancer are more dependent on ...

used as an anti-cancer agent. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1 (PARP-1). It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. The most common side effects include tiredness or weakness, nausea (feeling sick), increased levels of creatinine (which may indicate kidney problems) and liver enzymes in the blood (which may indicate liver damage), vomiting, anaemia (low red blood cell counts), decreased appetite, dysgeusia (taste disturbances), diarrhoea, thrombocytopenia (low levels of platelets) and abdominal pain (belly ache).

Medical uses

Rucaparib is indicated as monotherapy for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. In the United States, rucaparib is also indicated for the treatment of prostate cancer.

Pharmacology

Mechanism of action

Rucaparib inhibits "the contraction of isolated vascular smooth muscle, including that from the tumours of cancer patients. It also reduces the migration of some cancer and normal cells in culture." As a

, rucaparib is expected to be more effective in the 9% of pancreatic cancers with a

BRCA mutation A ''BRCA'' mutation is a mutation in either of the ''BRCA1'' and ''BRCA2'' genes, which are tumour suppressor genes. Hundreds of different types of mutations in these genes have been identified, some of which have been determined to be harmful, ...

(BRCA1 or BRCA2).

History

It was discovered as part of a collaboration between scientists working at the Northern Institute of Cancer Research and Medical School of

Newcastle University Newcastle University (legally the University of Newcastle upon Tyne) is a UK public research university based in Newcastle upon Tyne, North East England. It has overseas campuses in Singapore and Malaysia. The university is a red brick unive ...

and Agouron Pharmaceuticals in San Diego, California. It is being developed by

Clovis Oncology Clovis Oncology is an American pharmaceutical company which mainly markets products for treatment in oncology. Clovis was founded in 2009 and is headquartered in Boulder, Colorado. The company is a publicly traded company on NASDAQ under the sy ...

Society and culture

Legal status

In December 2016, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) granted an

accelerated approval The United States Food and Drug Administration (FDA) initiated the FDA Accelerated Approval Program in 1992 to allow faster approval of drugs for serious conditions that fill an unmet medical need. The faster approval relies on use of surrogate end ...

for use in cases of pretreated advanced

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

. It was designated an

orphan An orphan (from the el, ορφανός, orphanós) is a child whose parents have died. In common usage, only a child who has lost both parents due to death is called an orphan. When referring to animals, only the mother's condition is usuall ...

medicinal product in the European Union in October 2012. In March 2018, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regardin ...

(CHMP) adopted a positive opinion, recommending the granting of a conditional marketing authorization, intended for the treatment of relapsed or progressive ovarian cancer. It was approved for medical use in the European Union in May 2018. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Research

Clinical trials

After the FDA approval, TRITON2 and TRITON3 mCRPC studies were initiated in order to determine how patients with prostate cancer will respond to the rucaparib drug. The studies for these two trials are still going on and the estimated dates for the first results are range between 2019 and 2022." The ARIEL3 and ARIEL4 are two randomized, double-blind phase III studies. The ARIEL3 study was designed to evaluate the effect of the investigational agent as a maintenance treatment for the advanced platinum-sensitive ovarian cancer patients compared placebo after their response to at least two prior chemotherapies. The top-line results from the study were presented at the ESMO 2017 congress and right after that, it was published in the Lancet journal in September 2017. The findings showed significant improvement in progression-free survival (PFS) in patients treated with Rubraca than placebo. Recently, in October 2017, a supplemental sNDA for the rucaparib ARIEL3 maintenance treatment has been submitted to the FDA. Interim results from the ARIEL4 study to evaluate how patients will best respond to treatment with rucaparib compared with chemotherapy show a decrease in overall survival compared to standard of care. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged." A detrimental effect in terms of overall survival (OS) has been observed for rucaparib compared to the chemotherapy-containing control arm (19.6 months and 27.1 months respectively with a Hazard Ratio (HR) of 1.550 (95% CI: 1.085, 2.214), p=0.0161) following a planned interim analysis (IA) in the post-approval randomized controlled study CO-338-043 (ARIEL4).

References

External links

* * * {{Portal bar , Medicine Benzazepines Cancer treatments CYP2D6 inhibitors Tryptamines Lactams PARP inhibitors Fluoroarenes Orphan drugs Breakthrough therapy