7 days ago
J&J data support earlier use of combo pill in prostate cancer
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CHICAGO — A Johnson & Johnson drug currently used for advanced prostate cancer can help keep the disease from progressing in men who are at earlier stages and have certain genetic mutations, according to newly unveiled data from a Phase 3 clinical trial.
Results from this trial, named Amplitude, were released Tuesday at the American Society of Clinical Oncology's meeting in Chicago. They could potentially expand the number of people able to receive J&J's Akeega, a pill that combines the active ingredients from the medicines Zejula and Zytiga.
Akeega, along with hormone therapy, kept men with so-called BRCA mutations from getting sicker for longer than Zytiga and hormone therapy, reducing the relative risk of disease progression by nearly half. The combination also reduced by 56% the risk that BRCA-positive participants in the study experienced symptoms of disease progression.
Akeega is already approved for men whose disease stops responding to hormone therapy if they have BRCA mutations, which often signal a more aggressive cancer. This stage of disease, classified as 'castration resistant,' is considered to be advanced.
Akeega's constituent drug components target the proteins PARP and CYP17, respectively. Drugs aimed at CYP17 have been used in prostate cancer for more than a decade, while PARP inhibitors are more recent arrivals. However, in prostate cancer, PARP blockers are largely used in the castration-resistant setting, where testosterone suppression no longer keeps the disease in check.
Some physicians and drugmakers have explored moving treatment to early-stage disease as a way of helping patients live longer. Amplitude was set up to test that hypothesis.
'The challenge is that when we use PARP inhibitors as monotherapy at the end of the treatment sequence, resistance rapidly develops, and the median time to radiographic progression-free survival is shorter than 12 months,' said Gerhardt Attard, a professor of medical oncology at University College London and lead author of the study, in a press conference presenting the data. 'This group of patients have poor outcomes, significantly worse outcomes than other patients.'
Bradley McGregor, a genitourinary specialist with Dana-Farber Cancer Institute, said the study results will help clear up debate over where PARP inhibitors fit into treatment of people with hormone-sensitive disease. 'This data is quite compelling for the BRCA 1/2 patients where that magnitude of benefit is higher,' he said.
Amplitude enrolled men with a broader set of mutations to homologous recombination repair, or HRR, genes, of which BRCA is one. The benefit in the overall population was smaller, with Akeega reducing the risk of radiographic progression by 37% and symptomatic progression by half.
Akeega is currently approved only for the narrow BRCA-mutated population. Of the PARP inhibitors on the market, only AstraZeneca's Lynparza has won clearance for the broader HRR population, but its use is reserved for castration-resistant disease.
Mark Wildgust, J&J's global medical affairs vice president for oncology, said the HRR results from Amplitude should stimulate some discussion with the Food and Drug Administration. The company must keep working with regulators 'to see if there is room or comfort to expand to that broader population,' he said.
Trial investigators also analyzed results by specific HRR mutations beyond BRCA. With some, like one called PALB2, patients didn't see any benefit, Wildgust said. 'I think with smaller patient groups, it's a bit more difficult,' he added.
Physicians will need to be able to identify the patients most likely to benefit, should Akeega gain an expanded approval in earlier-stage prostate cancer. 'You don't know if you don't test,' McGregor said.
Akeega first won approval in 2023. Johson & Johnson didn't report annual sales for the drug in 2024.
GSK has some rights to Zejula, Akeega's PARP-inhibiting ingredient, by way of its 2019 acquisition of the drug's developer, Tesaro Bio. J&J had previously licensed rights to niraparib in prostate cancer specifically, allowing it to market Akeega.
