Ipatasertib (Roche) is a highly selective, ATP-competitive Akt inhibitor that preferentially targets active, phosphorylated Akt. Akt is dysregulated in a number of malignancies through loss of the tumor suppressor phosphatase and tensin homolog (PTEN), acquisition of activating mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) or AKT1, as well as amplification of PI3K.
Roche is investigating ipatasertib as part of a combination with Zytiga (abiraterone acetate; Johnson & Johnson/AstraZeneca) in asymptomatic or mildly symptomatic, previously untreated metastatic castration-resistant prostate cancer patients. Late-phase data are needed to determine the potential of ipatasertib in this indication, but targeting the PI3K/Akt/mammalian target of rapamycin (mTOR) pathway is a novel approach, and, if viable, could lead to further division of the prostate cancer treatment paradigm to include targeting patients with PI3K/Akt/mTOR abnormalities. Additionally, the success of Zytiga could be used to leverage the uptake of ipatasertib, but the combination will have to demonstrate strong efficacy and tolerability in order to justify its probable high price tag.
Triple-negative breast cancer is associated with activating PI3KCA or AKT1 mutations and deficient PTEN expression, both of which can lead to activation of the Pl3K/Akt/mTOR pathway. Additionally, signaling in the Pl3K/Akt/mTOR pathway has been shown to increase following chemotherapy, which is a standard regimen within the breast cancer treatment paradigm.
4 Drug Overview
5 Product Profiles
5 ipatasertib : Breast cancer: triple-negative
12 ipatasertib : Prostate cancer
LIST OF FIGURES
10 Figure 1: Datamonitor Healthcare’s drug assessment summary of ipatasertib for TNBC
10 Figure 2: Datamonitor Healthcare’s drug assessment summary of ipatasertib for TNBC
17 Figure 3: Ipatasertib for prostate cancer – SWOT analysis
18 Figure 4: Datamonitor Healthcare’s drug assessment summary of ipatasertib for prostate cancer
19 Figure 5: Datamonitor Healthcare’s drug assessment summary of ipatasertib for prostate cancer
21 Figure 6: Ipatasertib sales for prostate cancer across the US, Japan, and five major EU markets, by country, 2017–26
LIST OF TABLES
6 Table 1: Ipatasertib drug profile
8 Table 2: Late-phase trials of ipatasertib for TNBC
9 Table 3: Ipatasertib for TNBC – SWOT analysis
12 Table 4: Ipatasertib drug profile
14 Table 5: Ipatasertib Phase III trial in prostate cancer
16 Table 6: Ipatasertib Phase II data in prostate cancer
22 Table 7: Ipatasertib sales for prostate cancer across the US, Japan, and five major EU markets, by country ($m), 2017–26
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