Efmarodocokin alfa

Roche also pulled a phase 1 trial of efmarodocokin alfa in aGVHD from its pipeline. Roche’s long-stuttering attempt to bring the cancer drug candidate ipatasertib to market has run out of steam. After multiple clinical setbacks, the Swiss pharma giant has dropped (PDF) a phase 3 prostate cancer trial—and sent its acute graft-versus-host disease (aGVHD) prospect packing at the same time. Ipatasertib is a small molecule inhibitor of AKT, part of a signaling pathway implicated in the progression of prostate cancer and other tumor types. The candidate, which emerged from a collaboration between Array BioPharma and Roche’s Genentech unit, advanced into phase 3 trials in breast and prostate cancer but delivered underwhelming data. Roche reported failures in two breast cancer indications in 2020 and 2021. Things went slightly better in a prostate cancer trial that delivered topline data in 2020, with the study hitting its co-primary endpoint in a subset of patients but failing in the broader population. After the primary progression-free survival readout, Roche continued to collect overall survival (OS) data. Subsequent updates suggested ipatasertib was dead in the water, with Roche reporting no significant improvement in OS at the second interim analysis last summer. In September, the U.K. cost watchdog said Roche was working toward final OS analysis in mid-2023 but had dropped plans to seek approval. Roche confirmed the end of ipatasertib on Thursday by listing the prostate cancer study among its newly abandoned phase 3 programs. Ipatasertib sits alongside Roche’s previously disclosed termination of the gantenerumab Alzheimer’s disease trial on the list. The update also features one early-phase termination. Roche has pulled a phase 1 trial of efmarodocokin alfa in aGVHD from its pipeline. The drug candidate, also known as UTTR1147A, is a recombinant fusion protein that Roche took into phase 2 as a treatment for ulcerative colitis and Crohn’s disease. However, having failed to make the grade in those indications or aGVHD, the asset has landed on the scrapheap.

Over the past few years, Roche has released news about its AKT inhibitor ipatasertib in drips — most of them negative. The drug yielded mixed data in a key prostate cancer trial, Phase III flops in triple-negative breast cancer forced the pharma giant to pull the plug there, and in mid-2022 Roche trimmed two more early-stage indications in prostate cancer after completing the trials. Now, the last piece of the program is gone. Roche is officially scrapping the combination of ipatasertib and abiraterone, which was in a Phase III trial for first-line castration-resistant prostate cancer. It’s one of several late-stage programs Roche is sweeping out of the pipeline in its Q4 housecleaning exercise, alongside a trio of Tecentriq combos, the failed Alzheimer’s candidate gantenerumab and a drug for idiopathic pulmonary fibrosis. Separately, the company is dropping a Phase I compound for acute graft-versus-host disease. A Roche spokesperson confirmed to Endpoints News that “we don’t have any further projects ongoing with ipatasertib.” Although the Phase III IPATential150 study met its co-primary endpoint of radiographic progression-free survival in June 2020, it missed the key endpoint of overall survival at the second interim analysis. The spokesperson added that the safety profile of the ipatasertib/abiraterone combo was consistent with that observed at the primary analysis. Designed to block the PI3K/AKT pathway, ipatasertib arose from a partnership that Roche’s Genentech struck with Array BioPharma before Pfizer bought them out, and once inspired high hopes as a targeted approach. In the same presentation, Roche disclosed that it slammed the brakes on a Phase III study in idiopathic pulmonary fibrosis after a recent futility analysis suggested it’s unlikely to meet the primary endpoint. RG6354, which is also dubbed PRM-151 or zinpentraxin alfa, was the lead drug from Roche’s 2019 buyout of Promedior , for which it paid $390 million in cash upfront. Despite the setback, Roche still lists that program as a potential drug for myelofibrosis, with a filing expected in 2025 or later. Then there are three Phase III trials for the PD-L1 inhibitor Tecentriq being cut, in frontline metastatic urothelial carcinoma (Tecentriq + chemo), second-line non-small cell lung cancer (Tecentriq + Cabometyx) and second-line HER2-positive, PD-L1-positive metastatic breast cancer (Tecentriq + Kadcyla), respectively. Also exiting the pipeline are trials for gantenerumab, an anti-amyloid antibody, in preclinical Alzheimer’s and prodromal to mild Alzheimer’s — a reflection of Roche’s previously disclosed decision to stop all studies in the wake of a Phase III failure . Finally, Roche said it’s shutting down an IL-22 fusion protein, known as RG7880 or efmarodocokin alfa, that was being tested for the prevention of acute graft-versus-host disease in patients undergoing bone marrow transplant. The spokesperson cited “strategic reasons” for discontinuing the development, noting that “safety did not play any part in this decision.” Data from the Phase Ib study will be published.