J&J gets restricted label for PARP drug Akeega in EU

EMA decision

Johnson & Johnson’s entry into the PARP inhibitor market with prostate cancer therapy Akeega has started with a disappointing ruling in the EU.

The EMA’s human medicines committee has recommended approval for Akeega, a fixed-dose combination of J&J’s PARP drug Zejula (niraparib) and androgen inhibitor Zytiga (abiraterone acetate), in patients with metastatic castration-resistant prostate cancer (mCRPC).

In a setback for J&J’s Janssen-Cilag unit, however, the CHMP has said it recommends limiting use of Akeega to patients with BRCA1/2 mutations, which will put the drug at a disadvantage against AstraZeneca and Merck & Co’s rival PARP inhibitor Lynparza (olaparib).

In December, AZ and Merck claimed EU approval for the combination of Lynparza with Zytiga in an all-comer mCRPC patient population, allowing the regimen to be used without the need to test for mutations.

Janssen said that if fully approved by the European Commission – which usually follows a CHMP recommendation – Akeega will be the first dual action tablet in the EU for first-line treatment of adults with BRCA-positive mCRPC.

The question now is whether the convenience of a two-in-one tablet will be enough to offset the need for genomic testing of tumours and encourage take-up of the new drug.

J&J has rights to niraparib in prostate cancer under the terms of a licensing deal with its original developer Tesaro, signed in 2016, ahead of Tesaro’s acquisition by GSK. Rights to all other indications – including ovarian, fallopian tube, and peritoneal cancers – are owned by GSK.

The CHMP recommendation follows a phase 3 trial of Akeega, called MAGNITUDE, which revealed that the addition of niraparib to Zytiga plus prednisone or prednisolone significantly improved radiographic progression-free survival (rPFS) by 47% compared to standard of care in untreated mCRPC patients with BRCA1/2 mutations.

Updated results from MAGNITUDE were reported at the ASCO GU congress earlier this month, showing a trend towards improved overall survival, but no significant effect of the drug combination in mCRPC patients without homologous recombination repair (HRR) mutations, of which BRCA accounts for around half.

J&J and the investigators said the results were evidence that genomic testing of mCRPC patients remains critical.

“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,” commented Martin Vogel, Janssen-Cilag’s head of oncology for the EMEA region.

“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,” he added.

Analysts think a stronger challenge to Lynparza in first-line mCRPC could come from another PARP drug, Pfizer’s Talzenna (talazoparib) combined with Xtandi (enzalutamide), which reported new data from the TALAPRO-2 study at ASCO GU, including a 37% reduction in rPFS in an all-comer population.