News
Article
FDA Grants Amezalpat Orphan Drug Designation for Treatment of Hepatocellular Carcinoma
Author(s):
Key Takeaways
- Amezalpat received FDA orphan drug designation for hepatocellular carcinoma, highlighting its potential in addressing limited treatment options for this challenging disease.
- In a phase 1b/2 trial, amezalpat combined with atezolizumab and bevacizumab improved median overall survival by 6 months in HCC patients.
The new designation for the selective PPAR⍺ antagonist follows positive phase 1b/2 clinical trial results.
The FDA granted Tempest Therapeutics orphan drug designation (ODD) to amezalpat (TPST-1120), an oral, small molecule, selective PPAR⍺ antagonist to treat patients with hepatocellular carcinoma (HCC), according to a news release from Tempest.1
Hepatocelluar carcinoma is a common form of liver cancer. | Image Credit: © LASZLO | stock.adobe.com
HCC presents a challenge for those diagnosed and has been associated with poor prognoses and limited treatment options, especially in advanced-stage disease. HCC is the most common form of primary liver cancer and typically occurs in the context of chronic liver diseases such as hepatitis B or C or cirrhosis. Now, a new treatment is poised to have continued development with the aid of the FDA’s ODD, which allows Tempest to receive certain benefits to continue studying amezalpat.1,2
“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,” Sam Whiting, MD, PhD, chief medical officer of Tempest, said in the news release. “The team continues to prepare for a pivotal phase 3 study for amezalpat in first-line HCC patients.”1
Across multiple efficacy and safety end points in a global, randomized, phase 1b/2 clinical trial that evaluated amezalpat plus standard-of-care atezolizumab (Tecentriq; Genentech) and bevacizumab (Avastin; Genentech) versus atezolizumab and bevacizumab alone as a first-line treatment for patients with unresectable or metastatic HCC, positive results surrounded amezalpat’s administration in this population, bolstering the drug in its path to ODD. Investigators observed a 6-month improvement in median overall survival (OS) for patients treated with amezalpat combination therapy, with an objective response rate (ORR) of 30% in the amezalpat cohort.1
Furthermore, important subpopulations demonstrated preserved survival benefit from the addition of amezalpat, including those with PD-L1 negative disease and b-catenin mutated disease. This is consistent with the proposed mechanism of action of amezalpat, which aims to target both the patient’s immune system and dangerous tumor cells directly.1
Amezalpat’s development marks another step forward in the proliferation of new, innovative therapies for patients with HCC; specifically, the use of amezalpat as a combination therapy continues a trend of their development. The combination of atezolizumab and bevacizumab alone has been further studied in the IMbrave150 clinical trial as the drugs have become a standard-of-care for HCC. Furthermore, anti-CTLA-4 antibody tremelimumab-actl (Imjudo; AstraZeneca) was evaluated with durvalumab (Imfinzi; AstraZeneca) in the HIMALAYA study, with results showing improvement in OS compared with sorafenib.2
Pharmacists play a crucial role in evaluating drug combinations in the clinical pipeline for the treatment of patients with HCC. Often acting as the first point of contact for patient inquiries regarding which medications are best for them, pharmacists should educate themselves on drugs such as amezalpat as their development continues, while keeping tabs on the latest developments regarding new clinical practice or treatment guidelines for patients. In addition, given the common association of HCC with other conditions such as cirrhosis, it is essential for pharmacists to monitor patients for these related conditions and note their presence as a possible risk factor for HCC.
