The recent first global approval of rucaparib has been reviewed in detail in the First Global Approval report in Adis journal Drugs, based on the development milestones tracked in AdisInsight.
In December 2016, Rucaparib (Rubraca™), developed by Clovis Oncology, Inc., received its first global approval in the USA for the treatment of ovarian cancer, specifically as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies.1 A marketing authorisation application for rucaparib for the same indication has been submitted to the European Medicines Agency.
Rucaparib is an oral, small molecule, poly (ADP-ribose) polymerase (PARP) inhibitor that interferes with DNA repair in tumour cells, particularly those with mutation in the BRCA1 and/or BRCA2 genes or high genomic loss of heterozygosity. Rucaparib is the second PARP inhibitor to be approved for BRCA-mutated ovarian cancer. The first, olaparib (Lynparza®)2, received approval in 2014 for ovarian tumors that have been treated with three or more chemotherapies. A third PARP inhibitor, niraparib3, has shown promising results in some types of ovarian cancer and is currently under review by the FDA for potential approval.4
Ovarian cancer is the 7th most common cancer in women worldwide (18th most common cancer overall), with 239,000 new cases diagnosed in 2012.5 Quoted in a press release from the drug’s developer, Robert L. Coleman, MD of the MD Anderson Cancer Center in Houston, and one of the Principal Investigators in a pivotal trial leading to rucaparib approval, stated:
“Recurrent ovarian cancer remains a very difficult disease to treat, even among women who carry, or whose tumors have a mutation in the BRCA genes. Despite the available treatment options, few effective therapies are at our disposal. Thus, the opportunity to treat women with germline or somatic BRCA mutations with rucaparib after two prior lines of platinum-based therapy, represents a meaningful step forward for our patients.”
The approval application for rucaparib was granted breakthrough therapy designation, priority review status, and orphan drug designation, and therefore, may be contingent on the verification of its effects in confirmatory trials. Patients are selected for rucaparib treatment based on a US FDA-approved companion diagnostic (FoundationFocus™CDxBRCA).6,7 In a supporting statement, Michael Pellini, M.D., Chief Executive Officer of Foundation Medicine said:
“These simultaneous approvals by the FDA represent a step forward for women with advanced ovarian cancer, an area where there is a tremendous need for effective therapeutic approaches and efficient ways to identify those most likely to respond to PARP inhibitor therapy.”
Clovis is also exploring rucaparib in other solid tumor types with BRCA and homologous recombination deficiency (HRD) populations, including, breast, pancreatic, gastroesophageal, bladder and lung cancers.