The Janssen Pharmaceutical Companies of Johnson & Johnson recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended marketing authorisation for Akeega, a combination dual action tablet (DAT) given with prednisolone.
If approved the combination will be the first DAT available in the European Union for first-line treatment of adults with gene-mutated metastatic castration resistant prostate cancer (mCRPC) with BRCA1/2 (the genes that can offer protection from certain cancers) mutations.
Results from the phase 3 Magnitude study which showed Niraparib being added to AA plus P showed a significantly improved radiographic progression-free survival compared to standard care in untreated mCRPC patients with the mutations. The positive CHMP opinion was based on these results.
During their research Janssen found evidence that shows that prostate cancer is the most common cancer in men in Europe and despite treatment advances, for those whose cancer has progressed to mCRPC, the impact can be devastating with an average overall survival ranging from 13-36 months.
The company found that patients with mCRPC and BRCA gene mutations are more likely to have aggressive disease, poor outcomes and a shorter survival time. BRCA1/2 gene mutations have been identified in approximately 10-15 percent of patients with mCRPC.
Consultant oncologist, Elena Castro, who works at Sanitaria Hospital, Madrid, said: “Metastatic castration-resistant prostate cancer remains a lethal disease, with high unmet needs in terms of treatment options, particularly for patients with BRCA1/2 gene mutations.
“We’ve seen that in these patients, niraparib combined with abiraterone acetate and prednisone significantly reduces the risk of disease progression or death compared to AAP. This niraparib-based regimen is a welcomed targeted treatment option and, if approved, has the potential to impact the standard of care for men with mCRPC BRCA who are treated with first-line therapy.”
The positive CHMP opinion is based on results of the randomised, double-blind, placebo controlled which assessed whether the addition of Niraparib to AAP improved outcomes in those with first line mCRPC, with or without alterations in homologous recombination repair (HRR) associated genes. Patients with HRR gene alterations were randomised to receive niraparib 200 mg once daily plus AAP or placebo and AAP. In Magnitude, a total of 423 patients with HRR gene alterations were enrolled, 225 (53.2%) of whom had BRCA mutations. This is the largest cohort of BRCA1/2-positive patients with mCRPC.
“In recent years, we’ve focused on precision medicine in prostate cancer because we know patients with gene mutations, such as BRCA1/2, face a worse prognosis than those without,” said Martin Vogel, EMEA therapeutic area lead oncology, Janssen-Cilag GmbH.
“The positive CHMP opinion reinforces the benefit of this niraparib combination and marks an important milestone in addressing BRCA1/2 mutations as we continue to drive progress towards changing the outlook for patients with mCRPC.”
Niraparib is an orally administered, highly selective poly (ADP ribose) polymerase (PARP) inhibitor, currently being studied on an ongoing basis by Janssen and additional ongoing studies include the phase 3 Amplitude study.
“Prostate cancer is a heterogeneous disease made up of many biologically distinct subpopulations. The data from Magnitude supports the significant value of biomarker testing to identify the subgroup of patients most likely to derive a clinical benefit from a targeted treatment and overcome the poor prognosis of mCRPC with BRCA mutations,” said Kiran Patel, vice president, clinical development, solid tumors, Janssen research & development, LLC.
“At Janssen, we are dedicated to continued innovation in prostate cancer and now look forward to working with health authorities to bring this niraparib-based treatment option to patients as soon as possible.”