FDA awards ODD to Tempest's liver cancer therapy

The US Food and Drug Administration (FDA) has recently granted orphan drug designation to amezalpat (TPST-1120), an oral, selective peroxisome proliferator-activated receptor alpha (PPAR-α) antagonist developed by Tempest Therapeutics. This designation applies to the treatment of hepatocellular carcinoma (HCC), a rapidly advancing form of liver cancer.

This significant FDA designation follows promising outcomes from a randomized Phase Ib/II clinical study. In this study, amezalpat was evaluated in combination with the standard-of-care treatments atezolizumab and bevacizumab, and the combination was compared to the use of atezolizumab and bevacizumab alone. The research findings have indicated a notable six-month improvement in median overall survival for patients receiving the combination therapy.

The study reported a hazard ratio of 0.65, signifying a considerable reduction in the risk of death for participants treated with the amezalpat combination. Additionally, the objective response rate (ORR) favored the combination therapy, with a rate of 30% compared to 13% for the control group. Importantly, the survival benefit noted with the addition of amezalpat was consistent across key sub-groups of patients, including those with programmed cell death ligand 1 (PD-L1) negative disease and β-catenin mutated disease.

These findings align with the intended mechanism of action of amezalpat, which targets the cancerous cells while modulating immune-suppressive cells and affecting angiogenesis within the tumor’s microenvironment. The encouraging outcomes from this randomized study are further supported by data from a Phase I trial involving patients with heavily pretreated advanced solid tumors.

Sam Whiting, the head of Research and Development and chief medical officer at Tempest, commented on the recognition by the FDA: “Receiving orphan drug designation for amezalpat to treat HCC underscores the critical need for new treatment options for patients suffering from this historically hard-to-treat disease. Tempest is dedicated to developing groundbreaking cancer treatments that will improve patients’ lives, and with broad agreement in hand from both the FDA and EMA, the team continues to prepare for a pivotal Phase III study for amezalpat in first-line HCC patients.”

Tempest is actively preparing for a Phase III clinical trial to further evaluate amezalpat as a first-line treatment for patients with unresectable or metastatic HCC. This preparation follows an announcement last October where Tempest entered a collaboration with Roche to further explore amezalpat in combination with atezolizumab and bevacizumab. Under the terms of this agreement, Tempest will sponsor and lead the study, while Roche will provide atezolizumab on a global scale.

Hepatocellular carcinoma represents a particularly aggressive form of liver cancer that poses significant treatment challenges. The promising results from Tempest’s clinical studies and the subsequent orphan drug designation by the FDA highlight the potential for amezalpat to become a crucial treatment option for this challenging disease. As research progresses, there is hope that these innovative treatments will significantly improve the prognosis and quality of life for individuals affected by HCC.