Tempest Receives Orphan Drug Designation from the European Medicines Agency for Amezalpat for the Treatment of Patients with HCC

Rhea-AI Summary

Tempest Therapeutics (TPST) has received Orphan Drug Designation from the European Medicines Agency for amezalpat, their oral PPAR⍺ antagonist drug candidate for hepatocellular carcinoma (HCC) treatment. This follows previous FDA Orphan Drug and Fast Track Designations, highlighting the significant unmet need in liver cancer treatment. The designations were granted after positive Phase 1b/2 clinical trial results, where amezalpat combined with standard-of-care therapy (atezolizumab and bevacizumab) demonstrated superior outcomes. Key results include a six-month improvement in median overall survival with a hazard ratio of 0.65 compared to standard care alone. Notably, the survival benefit was maintained in key subpopulations, including PD-L1 negative disease patients, aligning with amezalpat's dual mechanism targeting both tumor cells and the immune system.

Positive

• Received EMA Orphan Drug Designation for amezalpat in HCC treatment
• Previously secured FDA Orphan Drug and Fast Track Designations
• Phase 1b/2 trial showed 6-month improvement in median overall survival (HR=0.65)
• Demonstrated efficacy in key subpopulations, including PD-L1 negative disease

Negative

• None.

Insights

Oncology and Biotechnology Regulatory Expert

EMA and FDA designations for Tempest's liver cancer drug demonstrate strong clinical potential with impressive 6-month survival improvement.

The European Medicines Agency's Orphan Drug Designation (ODD) for amezalpat represents a significant regulatory milestone for Tempest Therapeutics, complementing their existing FDA ODD and Fast Track Designation. These regulatory acknowledgments provide important benefits including potential market exclusivity and accelerated review pathways.

The clinical data supporting these designations is particularly compelling. The Phase 1b/2 study demonstrated a 6-month improvement in median overall survival with a hazard ratio of 0.65 when amezalpat was added to the standard-of-care regimen of atezolizumab and bevacizumab. In practical terms, this hazard ratio means approximately a 35% reduction in the risk of death compared to standard therapy alone.

What's especially noteworthy is the benefit observed in PD-L1 negative patients, a subpopulation that typically responds poorly to immunotherapy alone. This suggests amezalpat's dual mechanism – targeting both tumor cells directly and enhancing immune response – may provide advantages over current treatments.

Hepatocellular carcinoma remains a devastating cancer with limited treatment options and poor prognosis. As an oral, small molecule PPAR⍺ antagonist, amezalpat represents a novel approach in this difficult-to-treat disease. While these Phase 1b/2 results are promising, the company will still need to conduct larger pivotal trials to secure full regulatory approval.

For Tempest, a clinical-stage biotech company, these regulatory designations and positive efficacy signals significantly strengthen their development program and could accelerate amezalpat's path to market in this high-unmet-need indication.

• EMA Orphan Drug Designation (ODD) builds on U.S. Food & Drug Administration (FDA) ODD and Fast Track Designation, underscoring the urgent need for new treatment options
  
• The multiple regulatory designations were granted following strong positive results from a global randomized Phase 1b/2 study in first-line HCC demonstrating superior outcomes for amezalpat combination therapy across multiple study endpoints, including overall survival in both the entire population and key subpopulations, when compared to standard of care alone

BRISBANE, Calif., June 05, 2025 (GLOBE NEWSWIRE) -- Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company with a pipeline of first-in-class¹ targeted and immune-mediated therapeutics to fight cancer, today announced that the European Medicines Agency (EMA) has granted Orphan Drug Designation (ODD) to amezalpat (TPST-1120), an oral, small molecule, selective PPAR⍺ antagonist for the treatment of patients with hepatocellular carcinoma (HCC).

“We’re incredibly pleased to receive Orphan Drug Designation from the EMA, building on the momentum of regulatory support we've already received from the FDA,” said Stephen Brady, president and chief executive officer of Tempest. “These designations reflect the significant unmet need in liver cancer and reinforce our belief in the potential of amezalpat to make a meaningful difference for patients and families affected by this devastating disease.”

The company announced earlier this year that the FDA had granted both ODD and Fast Track Designation (FTD) to amezalpat to treat patients with HCC. These three designations follow positive data across multiple key study efficacy and safety endpoints from a global, randomized Phase 1b/2 clinical study evaluating amezalpat plus standard-of-care atezolizumab and bevacizumab versus atezolizumab and bevacizumab alone in the first-line treatment of patients with unresectable or metastatic HCC. Notable positive outcomes of the randomized comparison include a six-month improvement in median overall survival (OS) with a hazard ratio (HR) of 0.65 for patients receiving the amezalpat combination therapy. In addition, a survival benefit from patients receiving amezalpat was preserved in key sub-populations including PD-L1 negative disease, which is consistent with amezalpat’s proposed mechanism of action to target both the tumor cells directly and the patient’s immune system.

About Hepatocellular Carcinoma

HCC is an aggressive cancer with rising mortality and is projected to become the third leading cause of cancer death by 2030.² Every year, more than 900,000 people worldwide are diagnosed with HCC.³ Incidence and mortality are highest in East Asia and are increasing in parts of Europe and the US.⁴ In the US, HCC represents the fastest-rising cause of cancer-related death.³

Nine out of ten cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD) and cirrhosis resulting from these conditions.⁵

Even if diagnosed in the early stage, an estimated 70-80% of people with early-stage HCC experience disease recurrence following surgery.⁶ Early recurrence is associated with poorer prognosis and shorter survival.^5,7 Tumor size, number of tumors, and portal vein invasion are associated with an increased risk of recurrence.⁶

About Amezalpat

Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Data suggest that amezalpat treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In a global randomized Phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, the amezalpat arm showed clinical superiority across multiple study endpoints, including overall survival in both the entire population and key subpopulations, when compared to atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by additional positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors, including renal cell carcinoma and cholangiocarcinoma.

About Orphan Drug Designation

Orphan Designation is granted to therapies intended for the treatment, prevention, or diagnosis of life-threatening or chronically debilitating diseases that affect no more than two in 10,000 people in the European Union (EU) and for which no satisfactory therapy is available. The treatment must also provide significant benefit to those affected by the condition. EMA orphan drug designation provides certain benefits, including the potential for 10 years of market exclusivity following regulatory approval in the EU, reduction in regulatory fees and a centralized EU approval process.⁸

About Tempest Therapeutics

Tempest Therapeutics is a clinical-stage biotechnology company advancing a diverse portfolio of small molecule product candidates containing tumor-targeted and/or immune-mediated mechanisms with the potential to treat a wide range of tumors. The company’s novel programs range from early research to later-stage investigation in a randomized global study in first-line cancer patients. Tempest is headquartered in Brisbane, California. More information about Tempest can be found on the company’s website at www.tempesttx.com.

Investor & Media Contacts:

Sylvia Wheeler
Wheelhouse Life Science Advisors
swheeler@wheelhouselsa.com

Aljanae Reynolds
Wheelhouse Life Science Advisors
areynolds@wheelhouselsa.com

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¹ If approved by the FDA
² Rahib, L. et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74, 2913-2921 (2014).
³ World Health Organization. Liver Cancer Factsheet. Globocan. 2020. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf. Last accessed: April 2023.
⁴ Llovet, J. M., Kelley, R. K., Villanueva, A., et al. Hepatocellular carcinoma. Nature Reviews Disease Primers. 2021, 7(1), 6.
⁵ Office for Health Improvement & Disparities. Liver disease profiles: November 2021 update. Available at: https://www.gov.uk/government/statistics/liver-disease-profiles-november-2021-update/liver-disease-profiles-november-2021-update. Last accessed: April 2023.
⁶ Hack SP, Spahn J, Chen M et al. IMbrave 050: a Phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation. Future Oncology. 2020 May;16(15):975-989.
⁷ Saito A, Toyoda H, Kobayashi M et al. Prediction of early recurrence of hepatocellular carcinoma after resection using digital pathology images assessed by machine learning. Modern Pathology. 2021. 34, 417-425.
⁸ European Medicines Agency, "Orphan Designation." https://www.ema.europa.eu/en/human-regulatory-overview/orphan-designation-overview

FAQ

What regulatory designations has TPST's amezalpat received for HCC treatment?

Amezalpat has received Orphan Drug Designation from the EMA, and both Orphan Drug Designation and Fast Track Designation from the FDA for HCC treatment.

What were the key results from TPST's Phase 1b/2 trial of amezalpat?

The trial showed a six-month improvement in median overall survival with a hazard ratio of 0.65 for patients receiving amezalpat combination therapy compared to standard care alone.

How does TPST's amezalpat work in treating HCC?

Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist that targets both tumor cells directly and the patient's immune system.

What is the significance of amezalpat's efficacy in PD-L1 negative disease?

The survival benefit in PD-L1 negative disease patients demonstrates the drug's effectiveness across different patient subgroups, consistent with its dual mechanism of action.

What is the current treatment combination being tested for TPST's amezalpat in HCC?

Amezalpat is being tested in combination with standard-of-care atezolizumab and bevacizumab for first-line treatment of unresectable or metastatic HCC.