Efmarodocokin alfa

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.

Courtesy Smith Collection/Gado/Getty Images Roche is dropping its investigational AKT inhibitor ipatasertib, which was being assessed in a Phase III trial for castration-resistant prostate cancer, the company revealed Thursday in its 2022 full-year financial report. Aside from ipatasertib, Roche is also punting its early-stage candidate efmarodocokin alfa, which was in a Phase I trial for acute graft-versus-host disease, zinpentraxin alfa, a candidate for idiopathic pulmonary fibrosis, and its Alzheimer’s hopeful, gantenerumab. The company had previously announced it was discontinuing gantenerumab after the drug failed two Phase III studies. Ipatasertib is an orally administered small molecule inhibitor of three isoforms of the AKT protein, which in turn cripples a crucial signaling cascade in cancer cell growth and proliferation. Roche has had a difficult time trying to get ipatasertib through the clinic. In June 2020, its subsidiary, Genentech, reported the candidate hit only one of two co-primary endpoints in the Phase III IPATential150 trial in metastatic CRPC. Ipatasertib suffered another late-stage defeat in February 2021, when the company announced it was terminating the Phase III IPATunity130 study in hormone receptor-positive, HER2-negative advanced breast cancer. The candidate fell short of both efficacy endpoints in that study. Roche brought zinpentraxin alfa into its fold in 2019 when it offered $1.4 billion to acquire fibrosis player Promedior. The candidate is a recombinant form of human pentraxin-2 and is being investigated as a novel anti-fibrotic immunomodulator. The candidate still has an ongoing Phase II trial in myelofibrosis. Meanwhile, efmarodocokin alfa is a recombinant human fusion protein that targets IL-22 to treat inflammatory diseases. Roche had previously discontinued a Phase II study where the candidate was being investigated as a potential treatment for COVID-19-related pneumonia. A Busy Year Ahead Despite terminating two programs, Roche is looking forward to several late-stage and regulatory milestones this year. Its Vabysmo (faricimab-svoa), for example, is awaiting U.S. approval for retinal vein occlusion, as is the subcutaneous route of Tecentriq (atezolizumab) administration. Roche’s investigational bispecific monoclonal antibody glofitamab is also slated for U.S. approval as third-line treatment in diffuse large B-cell lymphoma, while Polivy (polatuzumabvedotin-piiq), in combination with chemotherapy, is awaiting regulatory verdict as first-line therapy in this indication. As for pivotal readouts, Roche is awaiting data from four Phase III studies for Tecentriq, either as a monotherapy or in combination with standard chemotherapy or biologic treatments. Venclexta (venetoclax tablets), its lymphoma drug, is also set to wrap up two Phase III studies, one in multiple myeloma and myelodysplastic syndrome. Other drugs with upcoming Phase III readouts include Susvimo(ranibizumab injection) for diabetic retinopathy, Xolair (omalizumab) for food allergy and Alecensa (alectinib) for non-small cell lung cancer. Roche is also entering six new molecular entities into Phase I studies, including for retinal disease, cystic fibrosis and solid tumors.