FDA Grants Fast Track Status to Tempest's Amezalpat for Liver Cancer Treatment

Tempest Therapeutics, Inc., a biotechnology firm located in Brisbane, California, has achieved a significant milestone in the fight against hepatocellular carcinoma (HCC), a type of liver cancer. The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to amezalpat, also known as TPST-1120, an oral, small molecule selective PPAR⍺ antagonist. This designation is part of the FDA's effort to expedite the development of drugs that show promise in addressing unmet medical needs in serious conditions.

Sam Whiting, the Chief Medical Officer and Head of Research and Development at Tempest Therapeutics, expressed enthusiasm about the designation, highlighting its importance alongside the previously acquired Orphan Drug Designation. These acknowledgments underline the potential of amezalpat as a treatment option for individuals battling HCC. Tempest Therapeutics plans to collaborate with the FDA and international regulatory bodies to ensure the development and availability of amezalpat for patients in need.

The Fast Track Designation is the second regulatory acknowledgment for amezalpat. In January, the company announced that the FDA had granted it Orphan Drug Designation due to its promising results in a global randomized Phase 1b/2 clinical trial. This study evaluated the efficacy of amezalpat combined with standard therapies—atezolizumab and bevacizumab—compared to standard therapies alone in patients with unresectable or metastatic HCC. The combination therapy demonstrated notable success, including an increase of six months in median overall survival with a hazard ratio of 0.65. It was observed that this survival benefit was maintained across key subgroups, including patients with PD-L1 negative disease, aligning with amezalpat's mechanism of targeting tumor and immune cells.

Hepatocellular carcinoma is a particularly aggressive form of cancer, with increasing mortality rates. It is projected to become the third leading cause of cancer-related deaths worldwide by 2030. Annually, over 900,000 people are diagnosed with HCC, with the highest incidence and mortality rates observed in East Asia, followed by increasing numbers in parts of Europe and the United States. In the U.S., HCC is recognized as the fastest-growing cause of cancer-related deaths. The predominant risk factor for developing HCC is chronic liver disease, often caused by conditions such as chronic hepatitis B or C infections, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcohol-related liver disease, and cirrhosis.

Amezalpat works as an oral, small molecule selective PPAR⍺ antagonist. It has shown potential in treating cancer by directly targeting tumor cells and modulating immune-suppressive cells and angiogenesis within the tumor microenvironment. In clinical studies involving first-line HCC patients, the combination of amezalpat with atezolizumab and bevacizumab demonstrated superior clinical outcomes across numerous endpoints, including overall survival, as compared to the standard treatment alone. These findings are supported by additional positive results from a Phase 1 trial in patients with advanced solid tumors, such as renal cell carcinoma and cholangiocarcinoma.

The Fast Track Designation is designed to accelerate the development and review of drugs that address unmet medical needs in serious conditions. This designation allows for more frequent communication with the FDA during the drug development process, and it can also make the drug eligible for accelerated approval and priority review. Tempest Therapeutics is committed to advancing its diverse portfolio of small molecule candidates, aiming to deliver innovative treatments for various tumor types.