AKT, also known as Protein Kinase B (PKB), is overexpressed or activated in large number of human cancers, including breast, lung, gastric, ovary and pancreas. AKT inhibitor inhibits the activated form of AKT that leads to normal functioning of AKT kinases. AKT has three isoforms; AKT1, AKT2 and AKT3, which play an important role in regulation of diverse cellular functions such as metabolism, motility, cell survival, cell-cycle progression and transcription. AKT is also involved in promoting growth factor-mediated cell survival to promote cell proliferation and inhibition of apoptosis through the inactivation of pro-apoptotic proteins, such as mouse double minute 2 homolog (MDM2) and Bcl-2 antagonist of cell death (Bad). Since AKT pathway plays a critical role in regulation of cell’s apoptotic pathway, it is being studied extensively as a target for cancer therapy.
The AKT inhibitors pipeline has more than 15 drugs. In pipeline analysis, drugs are analyzed based on route of administration and molecule type. The pipeline is also analyzed on the basis of monotherapy and combination therapy, and different clinical phases including Phase III, Phase II, Phase I and Pre-clinical stage.
Phase III & Filed
Phase III clinical trial known for the comparison of new treatments with the standard treatment in which the safety, efficacy and side effects of new intervention is compared with the already existing treatment. The Phase III clinical trial takes around 2-3 years to complete and the total number of participants vary from 100-1,000. After the completion of Phase III stage, the company files New Drug Application (NDA) to the regulatory authorities known as filed stage. There is no AKT inhibitor drug in Phase III clinical trial and one drug is in filed stage. Novartis AG has filed NDA in U.S. for midostaurin, for the treatment of FLT3-mutated acute myeloid leukemia. The marketing authorization application has already been accepted by the European Medicines Agency for midostaurin for the treatment of FLT3-mutated acute myeloid leukemia.
Rexahn Pharmaceuticals, Inc. has developed Archexin, a phase II drug candidate for the treatment of renal cell carcinoma. Phase II clinical trial is the second phase that answer safety, efficacy and dosing of the new intervention. There are total 8 drugs present in phase II trial of AKT inhibitors. Phase II clinical trial take around 2 years to complete and between 100 – 120 patients participate in the Phase II trial.
Triciribine phosphate (PTX 200), a drug candidate of Prescient Therapeutics Ltd., is in phase I stage of development for the treatment of acute myeloid leukemia, recurrent or persistent platinum resistant ovarian cancer, breast cancer, lung cancer and esophageal cancer. There are 4 drugs present in Phase I clinical stage. In Phase I clinical trial, safety of the new intervention is determined. The trial takes around 1-2 years to complete and the total number of volunteers participating in the trial vary between 15 – 30.
ASN003, a drug candidate of Asana BioSciences, LLC, is in preclinical stage of development for the treatment of melanoma and colon cancer. There are 2 AKT inhibitor drugs present in preclinical trial. Preclinical study is also known as animal study. It is done before testing a drug in people to find out the toxicity profile of the drug. Preclinical study is of two types, including In vitro and In vivo.
Pipeline analysis provides description about the key companies which are developing AKT inhibitor drugs. Some of the key players actively involved in the research and development are AstraZeneca plc, Cellectar Biosciences Inc., GlaxoSmithKline plc, Novartis AG, Prescient Therapeutics Ltd and Asana BioSciences, LLC.