Aadi Bioscience is a clinical-stage biopharmaceutical company founded by Dr. Neil Desai, inventor of Abraxane (paclitaxel for injection, albumin-binding) and albumin technology platform, and is currently working on the development of nab-sirolimus (ABI-009, West (Romosalbumin-binding nanoparticle suspension for injection) is used for diseases driven by mTOR activation.
Recently, the company announced that it has initiated the submission of a new drug application (NDA) for nab-sirolimus to the United States Food and Drug Administration (FDA) for the treatment of advanced (metastatic or locally advanced) malignant perivascular epithelioid cell tumors (PEComa ), this is a rare sarcoma driven by mTOR activation, there is currently no approved treatment. The company expects to complete the NDA submission in the fourth quarter of 2020.
Peripheral vascular epithelioid cell tumor (PEComa) is a rare subtype of soft tissue sarcoma. The origin of the cell is unclear and can occur in almost any body part (usually the uterus, retroperitoneum, lung, kidney, liver, urogenital system, and gastrointestinal tract). Road), may have an invasive clinical process, including distant metastasis and eventual death. The cytotoxic chemotherapy commonly used for sarcoma shows very little therapeutic benefit for PEComa, and currently no drugs have been approved for this disease.
Malignant PEComas are often accompanied by mutations in the TSC1 and/or TSC2 genes, leading to activation of the mTORC1 pathway. Therefore, mTORC1 signal transduction is an effective target for the treatment of malignant PEComas.
Sirolimus (sirolimus), also known as rapamycin (rapamycin), is a commonly used specific mTOR inhibitor. Nab-sirolimus is a type of sirolimus-human albumin-binding nanoparticles, which showed significantly higher tumor accumulation, mTOR target inhibition and efficacy than sirolimus in preclinical models. In the United States, nab-sirolimus has been granted Breakthrough Drug Qualification (BTD), Fast Track Qualification (FTD), and Orphan Drug Qualification (ODD).
The long-term follow-up data of the AMPECT study (NCT02494570) published at the recent ASCO meeting showed that 31 RECIST patients receiving nab-sirolimus can evaluate advanced PEComa patients, and the independent review assessment confirmed that the overall response rate (ORR) was 39% (95% CI: 22%-58%), including 1 complete response (CR) and 11 partial response (PR). The median duration of remission has not yet been reached (range: 5.6-42.4 months or more). The remission duration of 50% of the responders was ≥ 25.8 months, and most of the responders were still receiving treatment.
Among patients with metastatic disease, ORR was 46% (12/26, 95% CI: 27%-67%). Among the locally advanced and inoperable patients, 2/5 (40%) were able to undergo surgery after tumor shrinkage, and currently remain disease-free for more than 3 years. The median progression-free survival (PFS) was 8.9 months (95% CI: 5.5-not achieved), and the 1-year overall survival rate was 89%.
In an exploratory analysis of a subset of patients with TSC2 mutations, the ORR of independent review was 89% (95% CI: 57%-99%). The safety of nab-sirolimus is considered acceptable in this population, and its safety is consistent with the safety of mTOR inhibitors.
Dr. Neil Desai, Chief Executive Officer of Aadi, said: "After obtaining BTD, FTD, and ODD certification, the NDA submission of nab-sirolimus is an important milestone for Aadi and is also towards the activation of treatment of highly unmet needs diseases through the established mTOR pathway. The goal is a step forward. We are proud to complete the AMPECT study, which is the first prospective clinical trial for advanced PEComa, and we will continue to quickly complete the NDA submission to bring this potential new treatment to patients."