First Global Approval

Yahiya Y. Syed1

ti Springer International Publishing Switzerland 2017

Abstract Rucaparib (RubracaTM) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by Clovis Oncology, Inc. (Boulder, CO, USA) for the treatment of solid tumours. It has been approved in the USA 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. A mar- keting authorization application for rucaparib for the same indication has been submitted to the European Medicines Agency. Rucaparib is also under phase II or III investigation in ovarian, breast and prostate cancer. This article summarizes the milestones in the develop- ment of rucaparib leading to this first approval for ovarian cancer.
1Introduction

Rucaparib (RubracaTM) is an oral, small molecule inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP-1, -2 and -3 [1, 2]. It is being developed by Clovis Oncology, Inc. (Boulder, CO, USA) for the

 
This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

& Yahiya Y. Syed [email protected]

treatment of solid tumours. PARP enzymes play a key role in DNA repair and inhibition of these enzymes forms toxic PARP-DNA complexes in cells, resulting in DNA damage, ultimately leading to cell death [1, 2]. PARP inhibition is synthetically lethal in cells with homologous recombina- tion deficiency (HRD), such as those with mutation in the BRCA1 and/or BRCA2 genes or high genomic loss of heterozygosity (LOH) [2, 3].

Oral rucaparib has been approved in the USA as monotherapy for the treatment of patients with delete- rious BRCA mutation (germline and/or somatic) associ- ated advanced ovarian cancer who have been treated with two or more chemotherapies [1]. Patients are selected for rucaparib treatment based on a US FDA- approved companion diagnostic (Sect. 2.5). Rucaparib received accelerated approval based on objective response rate (ORR) and duration of response seen in phase II trials (Sect. 2.3.1). Continued approval of rucaparib in this indication may be contingent upon verification and description of clinical benefit in confir- matory trials [1]. A marketing authorization application for rucaparib in ovarian cancer has been submitted to the European Medicines Agency.
Rucaparib is also under phase II or III investigation in ovarian, breast and prostate cancer. Use of an intravenous formulation of rucaparib for the treatment of malignant melanoma was explored early in the development, prior to the acquisition of rucaparib by Clovis Oncology [4], and has since been discontinued.

1.1 Company Agreements

Rucaparib was originated by Cancer Research Technology

1
Springer, Private Bag 65901, Mairangi Bay, Auckland 0754, New Zealand
owned by Cancer Research UK and was licensed to Agouron Pharmaceuticals (later Pfizer). In June 2011,
Breakthrough therapy designation in USA (Apr)
US FDA accepts NDA (Aug) Preregistration in EU (Oct) EMA accepts MAA (Nov)

Orphan Drug status in USA (Jul)
Orphan Drug status in EU (Sep)
Accelerated approval in USA (Dec)
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Dec NCT00664781 Jan

 

Phase II trials
Nov
Study 10 (NCT01482715)
Sep ARIEL2 (NCT01891344)
Jan ARIEL3 (NCT01968213)
Est Dec Est Mar
Est Jun

Phase III trials
Sep
ARIEL4 (NCT02855944)
Est Jun 2024
Key milestones in the development of oral rucaparib monotherapy for the treatment of ovarian cancer. Est estimated completion date, MAA marketing authorization application, NDA new drug application

 

Clovis Oncology entered into a license agreement with Pfizer under which Clovis Oncology gained rights for global development and commercialisation of rucaparib [5]. Pfizer has received an upfront fee and is eligible for milestone and royalty payments from Clovis Oncology [5]. Pfizer is not involved in the development of rucaparib any longer, but the agreement will remain effective until expiration of the royalty and sublicense revenue obliga- tions of Clovis Oncology to Pfizer.
In April 2012, Clovis Oncology gained from AstraZe- neca exclusive rights to patents and patent applications for PARP inhibitors (including rucaparib) in certain indica- tions. AstraZeneca has received an upfront fee and is eli- gible for milestone and royalty payments from Clovis Oncology [6]. Clovis Oncology signed a long-term manu- facturing agreement for rucaparib with Lonza in October 2016 [7].
2Scientific Summary

2.1Pharmacodynamics
cancer [12]. A single oral dose of 92 mg inhibited the enzyme activity by a mean C90% from pretreatment levels at 24 h post-dose; however, a continuous dosing schedule was necessary to maintain the inhibition [12].
Rucaparib showed PARP-dependent and -independent cytotoxic mechanisms in cancer cells [8, 13]. In vitro, rucaparib was more cytotoxic than olaparib [14]. The cytotoxicity of rucaparib is increased in cancer cells with mutations in the BRCA1/2 genes and other DNA repair genes [13, 15, 16]. Rucaparib reduced tumour growth in mouse xenograft models of human cancer with [10, 15, 16]
or without [1] BRCA mutations. An HRD signature (Sect. 2.3.1) and a two-gene (CYB5R2, GSTT1) signature [17]
have been shown to predict response to rucaparib.
Rucaparib showed synergistic or additive interactions with commonly used chemotherapeutic agents, in vitro and in vivo [13, 18–21]. It sensitized cancer cells to platinum therapy [16, 22], chemoradiotherapy [23], irradiation [24, 25] and radiopharmaceuticals [25, 26]. Rucaparib is known to induce vasodilation, which may increase accu- mulation of cytotoxic drugs in cancer cells by increasing tumour perfusion [27–29].
Rucaparib is a potent PARP inhibitor at nanomolar con- centrations [8], with potentially greater PARP inhibitory activity than olaparib or niraparib [9]. Following a single oral or intraperitoneal dose of rucaparib in tumour-bearing
O

H
N
H
C
3
CH3

mice, the drug accumulated and was retained in tumours, and inhibited PARP enzymes for 7 days [10]. Intravenous [11] or oral [12] rucaparib inhibited PARP-1 enzyme

F

N
H

N
H

CH3

HO
O
S
O

O

activity in peripheral blood lymphocytes from patients with metastatic melanoma [11], or advanced ovarian or breast
Chemical structure of rucaparib
Mechanisms of resistance to rucaparib therapy include recovery of HRD [30] and defects in non-homologous end joining [31]. Rucaparib is efficiently transported by mul- tidrug efflux transporters, such as BRCP and P-glycopro- tein, and therefore, they can restrict oral bioavailability and brain penetration of rucaparib [32, 33]. Rucaparib may partially offset its efficacy by activating the phos- phatidylinositol 3-kinase (PI3K)/AKT signalling pathway; overexpression of the INPP4B gene, which negatively regulates this pathway, enhanced the antitumor activity of rucaparib in cancer cells [34].

2.2Pharmacokinetics

All rucaparib pharmacokinetic data discussed herein are from patients with cancer. Rucaparib showed linear, dose- proportional and time-independent pharmacokinetics over a dose range of 240–840 mg twice daily [1]. Following the recommended 600 mg twice daily dosage, the median Tmax [time to maximal plasma concentration (Cmax)] was 1.9 h. When taken with a high-fat meal, Cmax and the area under the plasma concentration-time curve from time 0 to 24 h (AUC0–24) were increased by 20 and 38%, respectively, and Tmax was delayed by 2.5 h relative to dosing under fasted condition; however, the effect is not considered clinically significant and rucaparib can be taken with or without food. Rucaparib immediate-release tablet has a mean absolute bioavailability of 36% [1]. Following administration of 600 mg twice daily in a 28-day cycle, rucaparib steady state was observed on day 15 of cycle 1 [3]. At steady state, accumulation of rucaparib was 3.5 to 6.2 fold at tested dose levels [1].
Rucaparib had a volume of distribution of 113–262 L following a single intravenous dose of 12–40 mg [1]. At

therapeutic concentrations, in vitro plasma protein binding of rucaparib was 70% in human plasma, and the drug preferentially distributed into red blood cells (blood to plasma concentration ratio 1.83). In vitro, rucaparib was metabolized primarily by cytochrome P450 (CYP) enzyme CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Rucaparib steady-state concentrations did not differ markedly across CYP2D6 or CYP1A2 genotype subgroups [1].
Oral rucaparib had a mean terminal half-life of 17–19 h after a single 600 mg dose and an apparent clearance of 15.3–79.2 L/h after multiple doses of 600 mg twice daily [1]. After a single intravenous dose of rucaparib, 11% of the dose was recovered in the urine over 24 h, indicating that this is not the major excretion route of the drug [11].
Mild or moderate renal impairment increased rucaparib exposure by 15 and 32%, respectively, versus normal renal function; mild hepatic impairment did not markedly affect the pharmacokinetics of rucaparib [1]. Starting dosage adjustment is not recommended in these patients. The pharmacokinetics of rucaparib in patients with severe renal impairment (creatinine clearance \30 mL/min) and in those with moderate to severe hepatic impairment (total bilirubin [1.5 times the upper limit of normal) are unknown, and therefore, starting dosage recommendation is not available for these patients [1].
Interactions of rucaparib with enzymes and transporters were evaluated in vitro. Rucaparib is a substrate and inhibitor of BCRP and P-glycoprotein [1]. It inhibits (CYP1A2, CYP2C19, CYP2C9, CYP3A, and CYP2C8, CYP2D6, UGT1A1 to a lesser extent), induces (CYP1A2) or down-regulates (CYP2B6, CYP3A4) several CYP enzymes. Rucaparib inhibits several transporter proteins potently (MATE1 and MATE2-K), moderately (OCT1) or
Features and properties of rucaparib
Alternative names AG 014699; AG-14699; CO-338; PF-01367338; PF-1367338; RUBRACA; Rucaparib camsylate
Class 3-Ring heterocyclic compounds, antineoplastics, azepines, indoles, small molecules
Mechanism of action Poly(ADP-ribose) polymerase inhibitors
Route of administration Oral
Pharmacodynamics Shows antitumour activity in cells with mutations in the BRCA1/2 and other DNA repair genes
Pharmacokinetics Displays linear, dose-proportional, time-independent pharmacokinetics; Tmax 1.9 h

Most frequent adverse
events
Nausea, fatigue (including asthenia), vomiting, anaemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhoea, thrombocytopenia, dyspnoea, increase in creatinine, ALT, AST and cholesterol, and decrease in haemoglobin, lymphocytes, platelets and neutrophils

WHO ATC code L01X-X55 (Rucaparib)
EphMRA ATC code L1 (Antineoplastics)

Chemical name
8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7-
dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt
weakly (MRP4, OATP1B1, OATP1B3, OAT1 and OAT3). The clinical relevance of these interactions is not clear. Concomitant administration of rucaparib with proton pump inhibitors has no clinically meaningful change in rucaparib steady-state exposure [1].

2.2.3Therapeutic Trials

2.2.3.1Ovarian Cancer

Rucaparib efficacy data are available from fully published articles [3, 12], US prescribing information [1], a confer- ence presentation [35], posters [36, 37] and an abstract [38].
In a pooled analysis of ARIEL2 (NCT01891344) and Study 10 (NCT01482715), rucaparib treatment produced an ORR [assessed by the investigator using Response Evaluation Criteria In Solid Tumours (RECIST) 1.1] of 54% (95% CI 44–64) in 106 evaluable patients with high- grade ovarian cancer who had progressed on C2 prior platinum-based chemotherapies [1, 35]. Complete and partial responses were seen in 9 and 45% of patients, respectively [1, 35]. The median duration of response was 9.2 months (95% CI 6.6–11.6) [1, 35]. The median pro- gression-free survival (PFS) was 10.0 months (95% CI 7.3–12.5) and 41% of patients were progression-free at 12 months [35]. ARIEL2 was a two-part, single-group, open- label, multinational, phase II trial [3] and Study 10 was a phase I/II trial [36]. Women with recurrent ovarian cancer with a deleterious BRCA1/2 mutation (germline or somatic [3] or germline [36]) were among those included in these trials. All patients received rucaparib 600 mg twice daily as monotherapy until disease progression or unaccept- able toxicity [1]. This was the recommended phase II/III dose identified in the phase I portion of the Study 10 in patients with ovarian or other solid tumours (n = 56) [38].
In pooled subgroup analyses of ARIEL2 and Study 10, ORRs did not differ (95% CI overlapped) between germ- line and somatic mutations (53.4 and 46.2%), BRCA1 and BRCA2 mutations (53.7 and 53.8%), 2 and C2 prior chemotherapy (68.3 and 53.8%) or 2 and C2 prior plat- inum-based regimen (65.0 and 53.8%) subgroups [35]. In platinum-refractory, -resistant and -sensitive subgroups, the ORR (95% CI) was 0% (0.0–41.0), 25.0% (8.7–49.1) and 65.8% (54.3–76.1), respectively. In patients with a pro- gression-free interval (after the latest platinum therapy) of \6, C6 to 12, and [12 months, the ORR (95% CI) was 18.5% (6.3–38.1), 62.5% (48.6–75.1) and 73.9% (51.6–89.8), respectively [35].
ARIEL2 (part 1) results suggest that an HRD signature can be a predictive biomarker of response to rucaparib in women with ovarian cancer [3]. Patients were classified into three predefined subgroups: deleterious BRCA1/2

germline or somatic mutation (BRCA-mutant; n = 40); BRCA wild-type with high or low LOH [high and low LOH, respectively; n = 82 and 70]. The median duration of rucaparib treatment was 5.7 months. The median PFS (95% CI) was 12.8 months (9.0–14.7) in the BRCA-mutant, 5.7 months (5.3–7.6) in the high LOH and 5.2 months (3.6–5.5) in the low LOH subgroups. The median PFS was significantly longer in the BRCA mutant [hazard ratio (HR) 0.27; 95% CI 0.16–0.44; p \ 0.0001)] and high LOH (0.62; 0.42–0.90; p = 0.011) subgroups, compared with the low LOH subgroup. The proportion of patients with PFS (95% CI) at 12 months in these subgroups was 50% (33–65), 28% (18–39), and 10% (4–19), respectively [3].
In ARIEL2 (part 1), consistent with PFS, confirmed ORRs (by RECIST 1.1) were significantly higher in the BRCA-mutant (80%; p \ 0.0001) and high LOH (29%; p = 0.0033) subgroups than in the low LOH subgroup (10%) [3]. A similar trend in ORRs were seen when RECIST 1.1 plus cancer antigen (CA)-125 criteria were applied. The median duration of response was also signif- icantly (p \ 0.05) longer in the BRCA-mutant (9.2 months) and high LOH (10.8 months) subgroups than in the low LOH subgroup (5.6 months). ORRs were generally similar irrespective of whether the BRCA mutation was germline or somatic, or BRCA1 or BRCA2. Among patients with BRCA wild-type tumours, genomic LOH predicted response to rucaparib with a significantly greater sensitivity (78%) than a mutation in non-BRCA homologous recom- bination genes (11%; p \ 0.0001) or methylation of BRCA1 or RAD51C (48%; p \ 0.021) [3]. The HRD sig- nature identified in part 1 will be further refined (using a higher LOH cut-off) and prospectively applied to ARIEL2 (part 2) and ARIEL3 (Sect. 2.6) [3, 37].
In the phase II portion of the Study 10, rucaparib pro- duced an ORR of 67 and 77% by RECIST 1.1 and RECIST
1.1plus CA-125 criteria, respectively, in patients with ovarian cancer (n = 39 evaluable) [36]. In subgroup analyses, the ORR (by RECIST 1.1) was 67 and 73% in patients with BRCA1 (n = 27) or BRCA2 (n = 11) muta- tion, 64 and 82% in patients with a progression-free interval (after the latest platinum therapy) of 6–12 (n = 25) and [12 (n = 11) months, and 69% in those who had received C3 prior chemotherapy regimens (n = 13). The disease control rate (complete or partial response plus stable disease for [24 weeks) was 87% [36].
In an investigator-initiated trial (NCT00664781), a continuous dosing schedule of oral rucaparib (92–480 mg once daily or 240–600 twice daily within a 21-day cycle) was associated with disease control (complete or partial response plus stable disease for C12 weeks) in 12 of 13 patients with ovarian cancer [12]. This was an open-label, phase II trial in which 78 women with advanced breast or ovarian cancer harbouring proven germline BRCA1/2
mutations were treated with intermittent or continuous schedules of intravenous or oral rucaparib [12].

2.3.2 Other Malignancies

In an investigator-initiated phase II trial (NCT01074970), rucaparib (intravenous and then oral) plus cisplatin given after preoperative neoadjuvant therapy did not improve 2-year disease-free survival in patients with triple negative breast cancer [n = 128] (abstract presentation [39]). The dosage of rucaparib administered in this study was sub- stantially lower than the recommended phase II/III dose of oral rucaparib 600 mg twice daily (Sect. 2.3.1) [39].
In the RUCAPANC trial (NCT02042378), oral ruca- parib was associated with clinical benefit in some patients with relapsed pancreatic cancer and a known deleterious germline or somatic BRCA mutation [n = 19] (poster presentation [40]). The investigator-assessed ORR (by RECIST 1.1) was 15.8% (95% CI 3.4–39.6) and the disease control rate (complete or partial response plus stable dis- ease for C12 weeks) was 31.6% (95% CI 12.6–56.6). RUCAPANC was an open-label, phase II trial in which

patients received rucaparib 600 mg twice daily in 28-day cycles until disease progression [40].
In a phase II study sponsored by Pfizer, an intravenous formulation of rucaparib in combination with temozolo- mide was associated with confirmed partial response (17.4% of patients; 95% CI 7.9–31.6) and stable disease for C24 weeks (17.4%; 7.9–31.6) in some patients with metastatic melanoma (n = 46) [4]. The median PFS and overall survival was 3.5 (95% CI 2.0–6.2) and 9.9 (6.2–14.7) months, respectively. The 1-year survival rate was 40%. Rucaparib was administered at 12 mg/m2 1 h before temozolomide 200 mg/m2 (starting dosages) on days 1–5 in a 28-day cycle [4].

2.4Adverse Events

Monotherapy with oral rucaparib 600 mg twice daily had a manageable tolerability profile in women with high-grade ovarian cancer who had progressed on C2 prior platinum- based chemotherapies in the pooled analysis of ARIEL2 and Study 10 (n = 377) [1, 35]. The median duration of treatment was 5.5 months [1] and the median dose intensity
Key clinical trials of rucaparib
Drug(s) Indication Phase Status Location Trial identifier Sponsors

Rucaparib, chemotherapy Ovarian cancer III Recruiting Multinational NCT02855944 (ARIEL4) Clovis Oncology
Rucaparib, placebo Ovarian cancer III Ongoing Multinational NCT01968213 (ARIEL3) Clovis Oncology
Rucaparib Ovarian cancer II Ongoing Multinational NCT01891344 (ARIEL2) Clovis Oncology

Rucaparib Ovarian cancer, solid
tumours
I/II Ongoing Multinational NCT01482715 (Study 10) Clovis Oncology

Rucaparib
Ovarian or breast
cancer
II
Completed UK
NCT00664781
Cancer Research UK

Rucaparib ? bevacizumab Ovarian cancer II Planned NA NA NA
Rucaparib ? atezolizumab Ovarian cancer Ib Planned NA NA Clovis Oncology,
Genentech

Rucaparib, abiraterone acetate, enzalutamide, docetaxel
Prostate cancer III Recruiting Multinational NCT02975934
(TRITON3)
Clovis Oncology

Rucaparib
Prostate cancer
II
Recruiting Multinational NCT02952534
(TRITON2)
Clovis Oncology

Rucaparib
Breast cancer
II
Ongoing UK
EudraCT2014-003319-12
(RIO)
The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research

Rucaparib Breast cancer II Recruiting France NCT02505048 (RUBY) UNICANCER

Rucaparib ? cisplatin,
cisplatin
Breast cancer
II
Ongoing USA
NCT01074970 Hoosier Cancer Research Network

Rucaparib
Pancreatic cancer
II
Completed Multinational NCT02042378
(RUCAPANC)
Clovis Oncology

Rucaparib Solid tumours I Recruiting Hungary NCT02986100 (AME) Clovis Oncology
Rucaparib ? carboplatin Solid tumours I Completed UK NCT01009190 Clovis Oncology
NA not available
was 0.92 [35]. Treatment-related all-grade and grade C3 adverse events were reported in 96 and 47% of patients, respectively [35]. Adverse events led to dose interruption or reduction in 62% of patients, most commonly because of anaemia (27%) and fatigue/asthenia (22%) [1]. Adverse events led to treatment discontinuation in 10% of patients, most commonly because of fatigue/asthenia (2%) [1]. Eight patients (2%) died because of progression of malignancy and one patient because of sepsis, which was assessed by the investigator as not related to rucaparib [35].
In the pooled analysis, the most common (incidence C20% for all grade) treatment-emergent adverse events (all grade; grade 3–4) were: nausea (77%; 5%), asthenia/fa- tigue (77%; 11%), vomiting (46%; 4%), anaemia (44%; 25%), constipation (40%; 2%), decreased appetite (39%; 3%), dysgeusia (39%; 0.3%), diarrhoea (34%; 2%), abdominal pain (32%; 3%), dyspnoea (21%; 0.5%) and thrombocytopenia (21%; 5%) [35]. Laboratory abnormal- ities reported in C35% of patients included (any worsening grade; shift to grade 3–4): an increase in creatinine (92%; 1%), ALT (74%; 13%), AST (73%; 5%) or cholesterol (40%; 2%), and a decrease in haemoglobin (67%; 23%), lymphocytes (45%; 7%), platelets (39%; 6%) or neu- trophils (35%; 10%) [1]. AST and ALT levels normalised over time with continued treatment [35].
In the pooled analysis, myelodysplastic syndrome/acute myeloid leukaemia were reported in \1% of patients [35]. Therefore, patients should be monitored for haematological toxicity at baseline and monthly thereafter [1]. Based on its mechanism of action and data from animal studies, ruca- parib can cause embryo-foetal toxicity when administered to pregnant women [1]. Hence, contraception is advised in women of reproductive potential during and 6 months after rucaparib treatment [1].
At steady state, rucaparib 600 mg twice daily increased Fridericia’s formula-corrected QT interval from baseline by a mean 14.9 ms in patients with solid tumours [1].

2.5Companion Diagnostic

Foundation Medicine has developed a companion diag- nostic (FoundationFocusTM CDxBRCA) for rucaparib [41]. It is a next-generation sequencing-based in vitro device for the qualitative detection of BRCA1/2 sequence alteration in ovarian tumour tissue [41]. The test is approved by the US FDA for selecting patients for the treatment of ovarian cancer with rucaparib [1, 41].

2.6Ongoing Clinical Trials

The pivotal programme for rucaparib in ovarian cancer is ongoing and includes two phase III trials, ARIEL3 (NCT01968213) [3] and ARIEL4 (NCT02855944) [35].

These trials are evaluating rucaparib in maintenance (ARIEL3) or treatment (ARIEL4) settings. ARIEL4 will compare rucaparib with standard chemotherapy. ARIEL2 and Study 10 are also still ongoing. An investigator-initi- ated phase II trial is planned to evaluate rucaparib in combination with bevacizumab (as a first-line maintenance therapy) and a phase Ib trial is planned in collaboration with Genentech to investigate the combination of rucaparib with atezolizumab in women with advanced ovarian cancer [42].
With regard to other indications, phase II (TRITON2; NCT02952534) and phase III (TRITON3; NCT02975934) trials are investigating rucaparib in metastatic castration- resistant prostate cancer. In addition to NCT01074970, two other investigator-initiated phase II trials are evaluating rucaparib in breast cancer [RIO (EudraCT2014-003319- 12); RUBY (NCT02505048)]. The RIO trial is investigat- ing the activity of rucaparib using Ki67 as a surrogate marker in patients with primary, sporadic, triple-negative or BRCA1/2-positive breast cancer [43]. A phase I trial is investigating the absorption, metabolism and excretion of rucaparib following a single oral dose in patients with advanced solid tumours (NCT02986100). An additional phase I trial is investigating drug interactions of rucaparib with caffeine, digoxin, omeprazole, vitamin K or warfarin in patients with solid tumours (NCT02740712).
3 Current Status

Rucaparib received its first global approval on the 19th of December 2016 for ovarian cancer in the USA.

Disclosure The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Y.Y. Syed is a salaried employee of Adis, Springer SBM.
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