Puma Biotechnology has stepped forward to breathe new life into alisertib, acquiring the aurora kinase A inhibitor from Takeda Pharmaceuticals in a deal worth up to $294 million. The agreement includes a $7 million upfront payment, with potential milestone payments reaching $287 million plus royalties on future sales.
The acquisition marks a significant pivot for alisertib (formerly MLN8237), which had previously faced challenges in clinical development. The compound, originally one of the premier assets in Takeda's $8.8 billion acquisition of Millennium Pharmaceuticals in 2008, encountered a setback in 2015 when it failed to meet endpoints in a phase 3 peripheral T-cell lymphoma trial.
Strategic Focus on High-Need Cancer Indications
Puma Biotechnology plans to redirect alisertib's development toward three primary cancer indications where significant unmet medical needs persist:
- Hormone receptor-positive, HER2-negative breast cancer
- Triple-negative breast cancer (TNBC)
- Small cell lung cancer (SCLC)
The company's strategy is particularly focused on patients who have exhausted current treatment options. For breast cancer patients, alisertib's novel mechanism of action could provide a new alternative when resistance to existing therapies develops. Similarly, in SCLC, the drug could offer hope for patients who have progressed following platinum-based chemotherapy.
Scientific Rationale and Mechanism of Action
Alisertib targets aurora kinase A, an enzyme crucial for cell division and proliferation that is frequently overexpressed in cancer cells. Research has demonstrated that abnormal expression of this enzyme can drive tumor formation, while its inhibition can suppress cancer cell proliferation, migration, and tissue invasion.
"To date, alisertib has demonstrated strong evidence of anti-tumor activity, both as a single agent and in combination with other anticancer drugs," stated Alan Auerbach, CEO of Puma Biotechnology. This assessment is based on results from previously completed mid-stage trials.
Portfolio Enhancement for Puma
The acquisition strategically complements Puma's existing oncology portfolio, which includes Nerlynx (neratinib), an oral HER2 inhibitor approved for breast cancer. Alisertib becomes the company's second clinical-stage asset, joining PB357, an ERBB 2 receptor antagonist currently in preclinical development.
Development Strategy
While specific trial designs have not been announced, Puma's development strategy will likely focus on "molecularly defined" tumors that show particular sensitivity to aurora kinase A inhibition. This targeted approach could help overcome the efficacy challenges that have historically affected the aurora kinase inhibitor class, particularly in solid tumors.
