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35018611000001105

New Medicines

ZejulaAdvanced ovarian cancer - first-line maintenance therapy following first line platinum-based chemotherapy response

Information

Zejula
Licence extension / variation
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

Launched
Launched
Launched
October 2020
Oct 20The EU has approved niraparib oral, once-daily PARP inhibitor, as first-line monotherapy maintenance treatment for patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response after platinum-based chemotherapy [9].
Sep 20Recommended for EU approval by CHMP - the additional indication is "as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy" [8].
Apr 20Approved by FDA. [6]
Feb 20Filed in EU as a maintenance first-line therapy in patients with advanced ovarian cancer who responded to platinum-based chemotherapy regardless of biomarker status [5].
Feb 20US FDA accepts sNDA for niraparib as first line maintenance treatment of ovarian cancer [4].

Category

PARP [poly (ADP-ribose) polymerase] inhibitor
The UK incidence of OC is 21 per 100,000 people. 75% have advanced disease and up to 80% respond to first-line platinum chemotherapy; of these 55-75% relapse within 2 years.
Advanced ovarian cancer - first-line maintenance therapy following first line platinum-based chemotherapy response
Oral

Further information

Yes

Trial or other data

Oct 19GSK announced results from PRIMA (ENGOT-OV26/GOG-3012), the PIII randomised, double-blind, placebo-controlled study of niraparib as a maintenance therapy in women with 1st line ovarian cancer following a response to platinum-based chemotherapy. Niraparib treatment resulted in a 38% reduction in the risk of disease progression or death in the overall population (PFS, HR 0.62; 95% CI, 0.50–0.75; p<0.001) [3].
Jul 19GSK announce PIII PRIMA study met primary endpoint of a statistically significant improvement in PFS regardless of biomarker status [2].
Aug 18PIII PRIMA trial is active and no longer recruiting [1].
Apr 16PIII PRIMA trial to investigate whether the maintenance therapy of niraparib will extend the progression free survival in patients with first line ovarian cancer starts (PR30-5017C; NCT02655016). 620 patients will be recuirted in the US, Belgium, Czech Republic, Canada, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Norway, Poland, Russia, Spain, Switzerland, Ukraine and the UK. Primary outcome is progression free survival; collection of these data is due to complete Feb 20 [1].

ZejulaAdvanced ovarian cancer - tablet formulation for first- and second-line maintenance therapy

Information

Zejula
New formulation
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

None
Pre-registration (Filed)
Phase I Clinical Trials
Nov 21Currently pre-registration in EU (to introduce a new pharmaceutical form, 100 mg film-coated tablets). At the CHMP Oct 21 meeting, the Committee discussed the issues identified in the application, relating to quality and clinical aspects. The Committee adopted the CHMP recommendation and scientific discussion together with the list of questions Day 120 List) and a specific timetable. In Nov 21, the assessment procedure was restarted after receipt of responses to the Day 120 List of Questions [3].

Category

PARP [poly (ADP-ribose) polymerase] inhibitor. Proposed dosing regimen is two to three 100mg tablets once daily.
There are around 7,400 new ovarian cancer cases in the UK every year - that is 20 every day. Incidence rates for ovarian cancer have been projected to rise by 15% in the UK between 2014 and 2035, to 32 cases per 100,000 females by 2035 [1].
Advanced ovarian cancer - tablet formulation for first- and second-line maintenance therapy
Oral

Trial or other data

Oct 21Recruitment continues in PI (NCT03329001) study. Now due to complete collection of primary outcome data in Jan 22 [4].
Apr 21PI (NCT03329001) study is recruiting [2].
Nov 17PI trial to compare a niraparib tablet formulation with a niraparib capsule formulation in patients with advanced solid tumors starts (NCT03329001; 3000-01-004; 213362). The crossover, open, prospective, randomised trial is enrolling 208 patients in the US. This is a three stage study to evaluate the relative bioavailability (BA) and Bioequivalence (BE) of niraparib administered as a tablet formulation compared to the reference capsule formulation. Stage 3 evaluates the effect of a high-fat meal on niraparib pharmacokinetics (PK) following a single dose of the tablet. The Extension Phase of this study is to enable participants enrolled in the study to continue to receive treatment with niraparib tablets if they are tolerating it and, in the Investigator´s opinion, may receive benefit. Collection of primary outcome data is due to complete Jul 21 [2].

Zejula Metastatic castration-resistant prostate cancer - first-line in combination with abiraterone and prednisone

Information

Zejula
Licence extension / variation
Janssen
Janssen

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Phase III Clinical Trials
Apr 22Janssen reverses its decision and will pursue a licence for this indication including in the UK. Company has filed an MAA in the EU, supported by data from the PIII MAGNITUDE study [7,9].
Feb 21Development stopped. The company considers trial results are not consistent with their commercial ambition for the product [6].
Oct 19Janssen has exclusive rights to niraparib in prostate cancer [4].

Category

PARP [poly (ADP-ribose) polymerase] inhibitor
Prostate cancer is the most common cancer in men and makes up 26% of all male cancer diagnoses in the UK. The age-standardised incidence of prostate cancer in the UK in 2014 was 175 per 100,000 population [1].
Metastatic castration-resistant prostate cancer - first-line in combination with abiraterone and prednisone
Oral

Trial or other data

Feb 22Data announced from PIII MAGNITUDE study. The cohort of patients with prospectively-identified HRR gene alterations enrolled 423 patients, with patients randomised to receive the combination of niraparib and abiraterone acetate plus prednisone (combination arm [n=212]) or placebo and abiraterone acetate plus prednisone (control arm [n=211]). At 18.6-month median follow-up, patients in the combination arm of the cohort with HRR gene alterations showed a significant improvement in rPFS, with a reduction in the risk of progression or death of 27 percent (hazard ratio [HR] 0.73; p=0.022). This improvement was most pronounced in patients with BRCA1/2 gene alterations, where a 47 percent risk reduction was observed for rPFS (HR 0.53; p=0.001), as analyzed by blinded independent central review (BICR). A consistent but greater improvement was observed in investigator-assessed rPFS, which showed an overall 36 percent risk reduction in patients with HRR gene alterations (HR: 0.64; p=0.002), and a 50 percent risk reduction in patients with BRCA1/2 gene alterations (HR: 0.50; p=0.0006). The cohort without HRR gene alterations (n=233) met the predefined futility criteria in August 2020, showing no benefit from the treatment combination (HR>1) in the HRR biomarker negative population. Additionally, objective response rate was improved by the combination of niraparib and abiraterone acetate plus prednisone. Overall survival data were immature at this interim analysis and follow-up will continue for all secondary endpoints [8,9].
Nov 21Recruitment stopped in PIII MAGNITUDE study after only 765 participants enrolled, and collection of primary outcome data completed in Oct 21 [5].
Oct 20PIII MAGNITUDE trial is recruiting [3].
Feb 19PIII MAGNITUDE trial to compare niraparib in combination with abiraterone acetate and prednisone vs. abiraterone and prednisone in patients with metastatic castration resistant prostate cancer starts (NCT03748641; 64091742PCR3001; CR108534). 1,000 patients will be recruited in countries including the US & EU (plus UK). Collection of primary outcome date (radiographic progression-free survival) is due to complete Jul 22 [2].

Evidence based evaluations

Zejula Metastatic endometrial or ovarian carcinosarcoma - second-line in combination with dostarlimab

Information

Zejula
Licence extension / variation
GlaxoSmithKline
GlaxoSmithKline

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

An oral poly-(ADP-ribose) polymerase (PARP) inhibitor
Carcinosarcomas (CS) (malignant mixed Müllerian tumors) are highly aggressive and rare tumors with a worldwide annual incidence between 0.5-3.3 cases/100.000 women. Gynecological CS, i.e. ovarian CS and uterine CS, have a 5-year overall survival <10% and a poor prognosis. After initial treatment (surgery +/- adjuvant radiotherapies +/- chemotherapies), vast majority of patients relapse and receive diverse chemotherapy producing modest benefits, and nearly all patients will die [1].
Metastatic endometrial or ovarian carcinosarcoma - second-line in combination with dostarlimab
Oral

Zejula Metastatic hormone sensitive prostate cancer - with abiraterone

Information

Zejula
Licence extension / variation
Janssen
Janssen

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

PARP [poly (ADP-ribose) polymerase] inhibitor
Prostate cancer is the most common cancer in men and makes up 26% of all male cancer diagnoses in the UK. The age-standardised incidence of prostate cancer in the UK in 2014 was 175 per 100,000 population [1].
Metastatic hormone sensitive prostate cancer - with abiraterone
Oral