FDA Grants Nab-Sirolimus Priority Review for Advanced PEComa


The mTOR inhibitor nab-sirolimus may be the first agent to receive FDA approval as therapy specifically for perivascular epithelioid cell tumors.

A new drug application (NDA) for sirolimus albumin-bound nanoparticles for injectable suspension (nab-sirolimus; ABI-009; Fyarro) for the treatment of perivascular epithelioid cell tumors (PEComas) was accepted by the FDA and granted priority review, according to an announcement from the company responsible for developing the agent, Aadi Bioscience, Inc.1

Data supporting the NDA are from the phase 2 AMPECT clinical trial (NCT02494570), which is exploring the efficacy of nab-sirolimus as a single-agent in patients with advanced malignant PEComa. The Prescription Drug User Fee Act target date for this application is November 26, 2021.

“We are very pleased with FDA’s acceptance of our NDA with Priority Review for Fyarro in patients with advanced malignant PEComa, an ultra-rare sarcoma. If approved, Fyarro will be the first FDA-approved therapy for the treatment of patients with this disease,” Neil Desai, PhD, chief executive officer and president of Aadi Biscience, Inc, said in a statement. “We look forward to working with the FDA during its review and would like to thank the many patients, caregivers, and physicians whose contributions have been invaluable and allowed us to develop this important therapy. In parallel, we continue to work on our commercial preparations to ensure a timely launch for the PEComa patient population.”

Nab-sirolimus is an mTOR inhibitor that was developed for patients with alternations in this pathway and for whom other mTOR inhibitors have failed to result in desirable disease outcomes. Rolling submission of the NDA began in June 2020 following breakthrough therapy, fast track, and orphan drug designations for the agent.2

Long-term results of AMPECT that were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting indicated a confirmed overall response rate of 39% (n = 12/31; 95% CI, 21.8%-57.8%) by independent review.3 The trial was the first prospective study to specifically examine advanced malignant PEComas, with patients (n = 34) receiving intravenous nab-sirolimus at 100 mg/m2 weekly or every 2 to 3 weeks until disease progression or toxicity.

The primary end point was ORR by independent review with key secondary end points of duration of response (DOR), progression-free survival (PFS) at 6 months, PFS overall, overall survival (OS), and safety. Primary analysis was carried out in patients who had 6 months of treatment of more.

As of the cut-off of February 6, 2020, there were 31 patients evaluable for efficacy with 1 achieving a complete response (CR) and 11 with partial responses, with a majority of responses reached at the first post-baseline at week 6. The median time to response was 1.4 months (95% CI, 1.3-2.8). Stable disease was observed in 52% (n = 16/31) of patients, for a disease control rate of 71%. Only 10% of patients had progressive disease.

The 6-month PFS was 71% (95% CI, 47.7%-85.1%) and the median DOR was not reached by investigator assessment (range, 5.6-38.7+ months). Eight of 12 responders were still on therapy at 1 year and 5 were still on treatment after 2 years.

TSC2 loss-of-function mutations were correlated with response in 25 patients evaluable for mutations for a response rate of 89% in those with the driver (n = 8/9).


  1. Aadi Bioscience announces FDA acceptance and priority review for the new drug application of Fyarro for the treatment of advanced malignant PEComa. News release. Aadi Biosciences, Inc. July 26, 2021. Accessed August 4, 2021. https://bit.ly/3A8ubun
  2. Aadi bioscience initiates rolling submission of NDA to FDA for nab-sirolimus (ABI-009, Fyarro) for the treatment of advanced malignant PEComa. News release. Aadi Biosciences, Inc. June 25, 2020. Accessed August 4, 2021. https://bit.ly/3rQROEO
  3. Wagner AJ, Ravi V, Riedel RF, et al. Long-term follow-up for duration of response (DoR) after weekly nab-sirolimus in patients with advanced malignant perivascular epithelioid cell tumors (PEComa): results from a registrational open-label phase II trial, AMPECT. J Clin Oncol. 2020;38(suppl 15):11516. doi: 10.1200/JCO.2020.38.15_suppl.11516
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