FDA Grants Orphan Drug Status to Amezalpat for HCC Treatment

Tempest Therapeutics, Inc., a biotechnology company specializing in innovative cancer treatments, has announced that its investigational drug amezalpat (TPST-1120) has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA). Amezalpat, an oral small molecule designed to selectively antagonize PPAR⍺, is being developed to treat hepatocellular carcinoma (HCC), a particularly aggressive form of liver cancer.

Sam Whiting, the chief medical officer and head of research and development at Tempest, emphasized the importance of this designation, noting that it highlights the urgent need for new therapeutic options for HCC, a disease that remains challenging to manage effectively. Whiting mentioned that the company is preparing for a pivotal Phase 3 trial for amezalpat in treating first-line HCC patients, having secured broad agreement with both the FDA and the European Medicines Agency (EMA).

The FDA's decision follows encouraging results from a global randomized Phase 1b/2 clinical trial. This study compared the efficacy and safety of amezalpat combined with standard-of-care treatments atezolizumab and bevacizumab against the standard treatments alone in patients with unresectable or metastatic HCC. Patients receiving the amezalpat combination therapy demonstrated a six-month improvement in median overall survival, with a hazard ratio of 0.65, and an objective response rate of 30%, compared to 13% in the control group. Notably, the survival advantage was maintained in sub-populations with PD-L1 negative disease and b-catenin mutated disease, aligning with amezalpat's proposed mechanism of action targeting both tumor cells and the immune system.

Hepatocellular carcinoma is becoming a major health concern, with mortality rates on the rise. By 2030, it is anticipated to become the third leading cause of cancer-related deaths globally. Each year, over 900,000 cases are diagnosed worldwide, with East Asia showing the highest incidence and mortality rates. The United States is experiencing an increase in HCC cases, making it the fastest-growing cause of cancer-related death in the country.

The primary risk factors for HCC include chronic liver diseases such as hepatitis B and C infections, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD), and cirrhosis. Even when detected early, a significant proportion of patients with HCC experience disease recurrence post-surgery, leading to a poorer prognosis and reduced survival rates. Tumor characteristics like size, number, and portal vein invasion are potential predictors of recurrence risk.

Amezalpat functions as a selective PPAR⍺ antagonist and has shown promise in clinical studies by directly targeting tumor cells and modulating immune-suppressive cells and angiogenesis within the tumor microenvironment. The drug's clinical superiority was evident in the Phase 1b/2 trial when used alongside atezolizumab and bevacizumab, with notable positive outcomes in overall survival and response rates.

The FDA's Orphan Drug Designation program aims to support the development of therapies for rare conditions affecting fewer than 200,000 people in the United States. This designation offers various incentives, including tax credits for clinical testing, a waiver or reduction of FDA application fees, and seven years of market exclusivity upon approval.

Tempest Therapeutics, headquartered in Brisbane, California, is a clinical-stage biotechnology company committed to advancing a portfolio of small molecule candidates with tumor-targeted and immune-mediated mechanisms. The company's initiatives span from early research to later-stage clinical investigations, aiming to address diverse cancer types.