FDA Grants Fast Track Designation to Amezalpat for Treatment of Hepatocellular Carcinoma

The FDA has granted fast track designation (FTD) to amezalpat (TPST-1120), an oral, small-molecule, selective PPAR⍺ antagonist designed for the treatment of patients with hepatocellular carcinoma (HCC), according to a news release from Tempest Therapeutics. The new designation builds on a previously granted orphan drug designation (ODD) to amezalpat and strengthens the portfolio of the promising treatment option.^1,2

Hepatocellular carcinoma is a common form of liver cancer. | Image Credit: © Anna Baranova - stock.adobe.com

“We are thrilled to receive Fast Track designation from the FDA,” Sam Whiting, MD, PhD, chief medical officer and head of research and development at Tempest, said in the news release. “This designation, following the orphan drug designation granted last month, reinforces the promise of amezalpat as a potential treatment option for patients affected by HCC.”¹

As one of the most common forms of primary liver cancer, HCC often occurs as a complication of other chronic liver diseases, such as cirrhosis, hepatitis B, or hepatitis C. Though there are options to relieve the burden of symptoms, they remain limited and not meaningfully effective, especially for patients presenting with serious forms of HCC. Now, the issuing of both FTD and OTD allows for amezalpat to receive an expedited review process, with the eventual goal of full FDA approval.²

The new designation is based on positive data that met multiple key investigational safety and efficacy end points. In a global, randomized phase 1b/2 clinical trial, researchers assessed amezalpat combined with standard-of-care atezolizumab (Tecentriq; Genentech) and bevacizumab (Avastin; Genentech) against atezolizumab and bevacizumab alone as a first-line treatment for patients with unresectable or metastatic HCC. The administration of amezalpat in this population yielded positive results.²

In addition, investigators reported a 6-month increase in median overall survival (OS) for patients receiving amezalpat combination therapy, along with an objective response rate (ORR) of 30% in the amezalpat cohort. In an important development, key study subpopulations, including those with PD-L1 negative disease and β-catenin mutated disease, maintained a survival benefit with the addition of amezalpat.²

These results signify amezalpat is working as designed, both directly targeting malignant HCC tumor cells and modulating angiogenesis and immune suppressive cells in the tumor microenvironment. The data from the phase 1b/2 clinical trial are bolstered by additional positive results observed in a phase 1 clinical trial of patients with heavily pretreated advanced solid tumors, including cholangiocarcinoma and renal cell carcinoma.¹

HCC is projected to become the third leading cause of cancer death by 2030 as mortality rises due to the aggressive cancer. Mortality and incidence are reported to be the highest in East Africa, but rates are increasing in the US and parts of Europe. In the US alone, HCC represents the fastest-rising cause of cancer-related death. Chronic liver disease (CLD) causes cases of HCC 9 out of 10 times; in patients with CLD, their symptoms should be consistently monitored, with routine check-ups and scans undergone to ensure HCC has not developed.²

REFERENCES

1. Tempest Therapeutics. Tempest granted fast track designation from the U.S. Food and Drug Administration for amezalpat to treat patients with hepatocellular carcinoma. News Release. Released February 10, 2025. Accessed February 10, 2025. https://www.globenewswire.com/news-release/2025/02/10/3023370/0/en/Tempest-Granted-Fast-Track-Designation-from-the-U-S-Food-and-Drug-Administration-for-Amezalpat-to-Treat-Patients-with-Hepatocellular-Carcinoma.html

2. Halpern L. FDA grants amezalpat orphan drug designation for treatment of hepatocellular carcinoma. Pharmacy Times. Published January 9, 2025. Accessed February 10, 2025. https://www.pharmacytimes.com/view/fda-grants-amezalpat-orphan-drug-designation-for-treatment-of-hepatocellular-carcinoma