Capivasertib is a novel, highly potent, selective ATP-competitive pan-AKT kinase inhibitor that exerts similar activity against the three isoforms AKT1, AKT2 and AKT3. Positive data have emerged from early-phase trials, and several phase 3 trials are now underway. These phase 3 trials could provide the basis for regulatory approval of capivasertib in combination with fulvestrant as second or later-line treatment for metastatic HR-positive/HER2-negative breast cancer and in combination with paclitaxel as first-line treatment for locally advanced or metastatic triple-negative breast cancer.
Originating from a collaboration between AstraZeneca, Astex Pharmaceuticals Inc, the Institute of Cancer Research and Cancer Research Technology, capivasertib has shown promising results in early-phase trials, with clinical benefit to patients irrespective of their PIK3CA/AKT1/PTEN mutational status:
Patents estimated to expire beginning in 2028
How will capivasertib impact the market for breast cancer?
Owing to the large number of incident and recurrent cases, high treatment rates across the many lines of treatment in some patient segments, and typically long treatment durations, breast cancer is one of the largest therapy markets in oncology and is expected to grow from $22.6 billion in 2021 to $50.5 billion in 2031 in the G7 markets. Sales are expected to increase from $11.1 billion in 2021 to $27.7 billion in 2031 for HR-positive/HER2-negative breast cancer treatments and from $1.6 billion in 2021 to $6.8 billion in 2031 for triple-negative breast cancer treatments.
What gaps in treatment does capivasertib fill?
Triple-negative breast cancer is a particularly aggressive form of breast cancer characterized by a heterogeneous patient population with a lack of well-established predictive biomarkers. As such, targeted therapies are lacking as well as efficacious therapy options in general. For both metastatic HR-positive/HER-negative and triple-negative disease, capivasertib promises to advance and diversify treatment options for these difficult-to-treat patients.
What hurdles might it need to overcome to reach blockbuster status?
The market for triple-negative breast cancer treatments is expected to become increasingly competitive, with the booming drug development in this space owing to the high level of unmet need and lack of approved agents. Multiple drug classes are being investigated, including immune checkpoint inhibitors, antibody-drug conjugates, therapeutic vaccines, PARP inhibitors and CDK4/6 inhibitors. Since the majority of capivaserib’s sales are forecast to be derived from the metastatic HR-positive/HER2-negative setting, major hurdles in uptake and thus sales potential include competition from established earlier-to-market therapies in this setting and emerging novel therapies (e.g., oral selective estrogen receptor degraders [SERDs] and TROP2 inhibitors).
“The AKT inhibitors seem active, but they also have a lot of toxicity. The other issue is determining where these best sit in the treatment algorithm, given that breast cancer is becoming increasingly competitive as new agents are approved.”
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