Roche abandons AKT prostate cancer asset

Published: Feb 02, 2023

By Tristan Manalac

BioSpace

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.

Source: BioSpace