On November 25, Astrazeneca announced the success of its AKT inhibitor Capivasertib in the phase III CAPItello-281 study for the treatment of newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). Following the approval and launch of Capivasertib for breast cancer indications, this study further confirms the clinical value of AKT inhibitors.

As a drug that has shown potential in multiple cancers such as breast cancer, prostate cancer, and ovarian cancer, AKT inhibitors have a very broad market outlook. In recent years, more and more pharmaceutical companies have begun to focus on AKT inhibitors as an important target with cross-cancer therapeutic potential. Laike Pharmaceuticals is one of the top students in this field. Its core product, LAE002 (afuresertib), currently has two phase III studies in breast cancer and prostate cancer, second only to Astrazeneca in the AKT race.

Positive data on AKT inhibitor treatment for prostate cancer.

The results of Astrazeneca's phase III CAPItello-281 study show that, compared to the placebo group, patients in the Capivasertib group had a significantly longer rPFS (radiographic progression-free survival) at the 55th-month evaluation, with data showing both statistical and clinical significance. Although overall survival (OS) data were immature at the time of analysis, they also showed an early trend of improvement.

In terms of market space, prostate cancer is the second most common cancer in men and the fifth leading cause of cancer death in men globally. In 2022, over 1.4 million cases of prostate cancer were diagnosed globally, with approximately 0.397 million deaths.

In new mHSPC patients, approximately one-third have an expected survival time of only five years. mHSPC, as an aggressive cancer, typically has a poor prognosis. Around 0.2 million new cases are diagnosed each year, with about one-fourth of them being PTEN-deficient. The loss or dysfunction of the PTEN gene has a very detrimental effect on the prognosis of these patients, as it promotes cancer cell proliferation and leads to dysregulation of the PI3K/AKT signaling pathway, highlighting the urgent need in the market for effective treatment of these diseases.

In the field of prostate cancer, Laike Pharmaceuticals' investigational product LAE002 combined with LAE001 (CYP17A1/CYP11B2 dual inhibitors) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) after standard therapy received FDA approval in May 2024.

According to the international multicenter phase II clinical trial data of Laike Pharmaceuticals (LAE201), 40 subjects were enrolled at the recommended phase II dose. These subjects had progressed on 1-3 lines of standard treatment, including patients who had at least received 1st line abiraterone or second-generation AR antagonist therapy. The study showed positive treatment effects in the aforementioned mCRPC patients (regardless of PTEN status): as of November 21, 2023, the median rPFS was 8.1 months. This is a significant improvement compared to median rPFS of 2-4 months under past standard treatment for mCRPC patients, demonstrating good overall tolerability of the combination therapy with manageable adverse events that can be resolved post-treatment.

There is a huge potential for development in the treatment of breast cancer.

From a commercial perspective of AKT inhibitors, Capivasertib, as the world's first AKT inhibitor for breast cancer, was approved by the FDA in November 2023 and used in combination with fulvestrant to treat specific breast cancer patients. This not only provides patients with new and better treatment options but also brings significant commercial benefits to astrazeneca.

Data shows that Capivasertib achieved $0.27 billion in revenue in the first three quarters of 2024, with expected annual sales exceeding $0.4 billion. Such sales performance reflects both Capivasertib's market acceptance and highlights its market growth potential in the field of breast cancer treatment.

Lai Kai Medicine launched the key clinical trial AFFIRM-205 of LAE002 (Afuresertib) in May 2024 in China, in collaboration with fulvestrant, for the treatment of locally advanced or metastatic HR+/HER2- breast cancer in stage III patients with PIK3CA/AKT1/PTEN alterations. The project is progressing smoothly and ahead of schedule as planned.

Lai Kai Medicine announced the final results of the Phase Ib study at the European Society for Medical Oncology (ESMO) in September 2024: in 18 breast cancer patients with PIK3CA/AKT1/PTEN mutations, the median progression-free survival (PFS) was 7.3 months. This treatment showed positive anti-cancer efficacy and good tolerability and safety in both the overall population of 31 subjects from China and the USA, as well as in the subgroup with PIK3CA/AKT1/PTEN alterations.

Summary

Overall, astrazeneca's Capivasertib has demonstrated positive efficacy and good safety in prostate cancer treatment, as well as outstanding sales performance in the breast cancer treatment field in the first three quarters. This undoubtedly confirms the value and market potential of AKT inhibitors in clinical applications.

It is not difficult to see that the types of cancer targeted by AKT inhibitors not only have an urgent need in treatment but also have huge development space in the commercial market, indicating the important position of AKT inhibitors in the future cancer treatment field.

These positive signals also provide a positive market outlook for LAE002 in the hands of Laike Pharmaceuticals. As one of the only two AKT inhibitors in late-stage clinical development for the treatment of breast cancer and prostate cancer, on par with AstraZeneca's Capivasertib, the success of Capivasertib has set a benchmark for the AKT inhibitor market. The future growth potential of LAE002 from Laike Pharmaceuticals is promising.