Aucentra Therapeutics recently initiated a Phase II trial of auceliciclib in combination with temozolomide for recurrent or newly diagnosed glioblastoma patients in Australia. Auceliciclib is a CDK4/6 inhibitor and has proven its ability to overcome the blood-brain barrier (BBB) in preclinical models. Against this backdrop, auceliciclib could become a ground-breaking drug for glioblastoma if it is able to demonstrate clinical benefits and safety in ongoing clinical trials, says GlobalData, a leading data and analytics company.

According to GlobalData’s Pharma Intelligence Center, Australia saw 865 diagnosed incident cases of glioblastoma in 2021. Further, the five-year survival rate for glioblastoma is 4.6% in Australia as per the Australian Cancer Research Foundation. The BBB complex structure still remains a significant impediment to deliver effective therapeutic for the treatment of brain tumors. In the past, two CDK4/6 inhibitors Eli Lilly’s abemaciclib and palbociclib from Pfizer to treat glioblastoma failed in Phase II trials due to safety and efficacy concerns.

Anupama Mishra, Pharma Analyst at GlobalData, comments: “Glioblastomas are treated with surgery, chemotherapy and radiotherapy. There have been very few targeted therapies approved for glioblastoma treatment over the past four decades. This is mainly because of pipeline agents’ failures to meet trial endpoints and prove clinical benefits.  Furthermore, glioblastoma has the worst prognosis with patients having a life expectancy of 14-15 months post-diagnosis. Hence, it becomes very important to develop efficacious targeted therapeutics with low toxicity to reduce the unmet need. However, Aucentra’s claim that auceliciclib has an added advantage of high specificity owing to its low level of toxicity over other drugs such as chemotherapy remains to be proven in the ongoing trials.”

The University of South Australia (UniSA) and Aucentra Therapeutics have initiated the recruitment of up to 50 glioblastoma patients for the second phase of the trial.

The company is also evaluating auceliciclib as a monotherapy in a separate ongoing trial for patients with late-stage breast, lung, ovarian and colorectal cancer. Approximately 10-15% of people with stage IV breast cancer have brain metastases. Similarly, 10 % of newly diagnosed patients with non-small cell lung cancer (NSCLC) have brain metastases. Currently, there is a lack of therapies for the effective treatment of brain metastasis for these cancer patients.

Mishra concludes: “There exists a bright market opportunity for auceliciclib to be positioned as a viable alternative for brain tumors metastasized from other cancers including breast and lung if it demonstrates safety and efficacy in its ongoing clinical trials. Notably, temozolomide is the only effective recognized therapy for glioblastoma. Additionally, auceliciclib being an oral formulation (capsule) and with its proven ability to cross the BBB makes it a highly promising drug in the pipeline for glioblastoma treatment in Australia as well as globally.”