CHMP has recommended EU approval of senaparib for advanced ovarian cancer based on FLAMES data.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending marketing authorization for senaparib (Sepalna) as first-line maintenance treatment of advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer.1
The decision is based on findings from the phase 3 FLAMES trial (NCT04169997), in which single-agent senaparib (n = 271) reduced the risk of progression or death by 57% vs placebo (n = 133) in patients with newly diagnosed advanced ovarian cancer.1,2 More specifically, at the prespecified interim analysis, median progression-free survival (PFS) was not reached (NR) with senaparib vs 13.6 months with placebo (HR, 0.43; 95% CI, 0.32-0.58; P < .0001).
"The positive opinion from CHMP is a critical step towards market authorization by the European Commission, marking a significant milestone not only for senaparib,” said Sui Xiong Cai, PhD, chief executive officer of IMPACT Therapeutics in a news release.1
Notably, the
In the randomized, multicenter trial eligible patients were 18 years of age and had newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III to IV, high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer and a complete or partial response to first-line platinum-based chemotherapy.2,4 Patients also needed to have an ECOG performance status of 1 or less, a life expectancy of at least 16 weeks, and normal organ and bone marrow function.4
If patients had unclear BRCA mutation status received more than one cytoreductive surgery prior to randomization, FIGO stage I or II, or received chemotherapy for abdominal or pelvic tumors they were not included in the trial.
Patients received either oral senaparib at 100 mg once daily or matched placebo for up to 2 years or until disease progression or unacceptable toxicity.2
The primary end point of the trial was PFS by blinded independent central review. Key secondary end points included investigator-assessed PFS, safety, and time from randomization to treatment discontinuation or death.
Baseline characteristics revealed that patients had a median age was 55 years in the senaparib arm vs 54 years in the placebo arm. Most patients had an ECOG performance status of 1 (senaparib, 60.9%; placebo, 57.9%), serous histology (99.8%; 100%), and BRCA mutation–negative disease (65.3%; 66.9%). Absent gross residual disease after debulking surgery was reported in 77.6% patients in the senaparib arm vs 72.7% of those in the placebo arm. Most patients in both the senaparib arm (87.5%) and placebo arm (89.5%) experienced a complete response to platinum-based therapy.
Twelve-month PFS rates were 72.2% with senaparib compared with 53.7% with placebo; at 24 months, the respective rates were 63.0% vs 31.3%. In the BRCA-mutated subgroup, median PFS was NR with senaparib vs 15.6 months with placebo (HR, 0.43; 95% CI, 0.24-0.76; P = .0026). Respective median PFS values in each arm for those who were in the BRCA-negative subgroup were NR vs 12.9 months (HR, 0.43; 95% CI, 0.30-0.61; P < .0001).
Secondary end points favored senaparib, including investigator-assessed PFS (HR, 0.43; 95% CI, 0.32-0.57; P < .0001), and median time from randomization to discontinuation or death (HR, 0.68; 95% CI, 0.54-0.86; P = .0003).
Treatment discontinuation occurred in 72.7% of patients in the senaparib arm compared with 87.2% in the placebo arm, with reasons including disease progression (30.6%; 60.9%), completion of 2 years of treatment (25.1%; 16.5%), and adverse events (AEs; 4.4%; 0%).
Grade 3 or higher AEs were experienced by 66.3% of patients receiving senaparib vs 20.3% of those receiving placebo, and serious AEs occurred in 27.8% vs 3.8%. Treatment-emergent AEs (TEAEs) of any grade were reported in 99.6% and 97.7% of patient in each of the respective arms. The most common grade 3 or higher TEAEs with senaparib were anemia, thrombocytopenia, and neutropenia.
“The CHMP’s positive opinion marks an important next step in the regulatory process for this medicine. Our focus is now on using our market access, medical and launch capabilities to bring senaparib as a novel treatment option to patients in our territories,” said Stephan Eder, cheif executive officer of Pharamnovia, in a news release.
