Tempest Receives Orphan Drug Designation from the U.S. Food and Drug Administration for Amezalpat to Treat Patients with Hepatocellular Carcinoma (HCC)
Tempest Therapeutics announced that the FDA has granted Orphan Drug Designation to amezalpat (TPST-1120), an oral, small molecule, selective PPAR⍺ antagonist, for the treatment of patients with hepatocellular carcinoma (HCC).
According to Sam Whiting, M.D., Ph.D., this designation highlights the critical need for new treatments for this challenging disease. Tempest plans to proceed with a pivotal phase 3 study for amezalpat in first-line HCC patients.
The designation follows positive data from a global randomized Phase 1b/2 clinical study evaluating amezalpat plus standard-of-care atezolizumab and bevacizumab versus atezolizumab and bevacizumab alone in treating unresectable or metastatic HCC. Key results include:
- A six-month improvement in median overall survival (OS) with a hazard ratio (HR) of 0.65 for the amezalpat combination therapy.
- An objective response rate (ORR) of 30% compared to 13% for the control arm.
- Preserved survival benefit in key sub-populations, including PD-L1 negative disease and b-catenin mutated disease.
These outcomes are consistent with amezalpat’s mechanism of action, targeting both tumor cells and the patient’s immune system.
Tempest Therapeutics ha annunciato che la FDA ha concesso la designazione di farmaco orfano a amezalpat (TPST-1120), un antagonista selettivo della PPAR⍺, in forma orale, per il trattamento di pazienti affetti da carcinoma epatocellulare (HCC).
Secondo Sam Whiting, M.D., Ph.D., questa designazione mette in luce l'urgente necessità di nuovi trattamenti per questa malattia difficile. Tempest prevede di procedere con uno studio pivotale di fase 3 per amezalpat in pazienti con HCC in prima linea.
La designazione arriva dopo dati positivi provenienti da uno studio clinico globale randomizzato di fase 1b/2 che ha valutato amezalpat insieme all'atezolizumab e al bevacizumab standard, rispetto all'atezolizumab e al bevacizumab da soli, nel trattamento di HCC non resecabile o metastatico. I risultati principali includono:
- Un miglioramento di sei mesi nella sopravvivenza globale mediana (OS) con un rapporto di rischio (HR) di 0,65 per la terapia combinata con amezalpat.
- Un tasso di risposta obiettiva (ORR) del 30% rispetto al 13% per il braccio di controllo.
- Beneficio di sopravvivenza mantenuto in sub-popolazioni chiave, inclusa la patologia negativa per PD-L1 e quella mutata per b-catenina.
Questi risultati sono coerenti con il meccanismo d'azione di amezalpat, che mira sia alle cellule tumorali che al sistema immunitario del paziente.
Tempest Therapeutics anunció que la FDA ha concedido la designación de medicamento huérfano a amezalpat (TPST-1120), un antagonista selectivo de PPAR⍺, en forma oral, para el tratamiento de pacientes con carcinoma hepatocelular (HCC).
Según Sam Whiting, M.D., Ph.D., esta designación subraya la necesidad crítica de nuevos tratamientos para esta enfermedad desafiante. Tempest planea proceder con un estudio pivotal de fase 3 para amezalpat en pacientes con HCC de primera línea.
La designación sigue a datos positivos de un estudio clínico global randomizado de fase 1b/2 que evaluó amezalpat más el estándar de atención con atezolizumab y bevacizumab frente al atezolizumab y bevacizumab solos en el tratamiento de HCC irresecable o metastásico. Los resultados clave incluyen:
- Una mejora de seis meses en la supervivencia general mediana (OS) con una razón de riesgos (HR) de 0.65 para la terapia combinada con amezalpat.
- Una tasa de respuesta objetiva (ORR) del 30% en comparación con el 13% para el grupo de control.
- Beneficio de supervivencia preservado en subpoblaciones clave, incluida la enfermedad negativa para PD-L1 y la enfermedad mutada para b-catenina.
Estos resultados son consistentes con el mecanismo de acción de amezalpat, que ataca tanto las células tumorales como el sistema inmunológico del paciente.
템페스트 생명과학은 FDA가 아메잘파트(TPST-1120)에 대해 희귀의약품지정을 부여했다고 발표했습니다. 아메잘파트는 경구 투여 가능한 소분자 선택적 PPAR⍺ 길항제로, 간세포암(HCC) 환자 치료를 위해 개발되었습니다.
사믈 휘팅(Sam Whiting) 박사 말에 따르면, 이번 지정은 이 도전적인 질병에 대한 새로운 치료법의 절실한 필요성을 강조합니다. 템페스트는 첫 번째 치료제로서 HCC 환자에서 아메잘파트에 대한 결정적 3상 연구를 진행할 계획입니다.
이 지정은 아메잘파트와 표준 치료인 아테졸리주맙 및 베바시주맙의 조합이 단독 치료에 비해 재절제 불가능하거나 전이성 HCC 치료에 효과적이라는 긍정적인 데이터에 기반하고 있습니다. 주요 결과는 다음과 같습니다:
- 아메잘파트 조합 요법으로 중간 생존 기간이 6개월 개선되었으며, 위험 비율(HR)은 0.65입니다.
- 대조군에 비해 30%의 객관적 반응률(ORR)을 기록했습니다.
- PD-L1 음성 질환 및 b-카테닌 변이 질환을 포함한 핵심 하위 집단에서도 생존 이점이 유지되었습니다.
이 결과는 종양 세포와 환자의 면역계를 모두 표적으로 하는 아메잘파트의 작용 메커니즘과 일치합니다.
Tempest Therapeutics a annoncé que la FDA a accordé la dénomination de médicament orphelin à amezalpat (TPST-1120), un antagoniste sélectif de PPAR⍺ sous forme orale et de faible molécule, pour le traitement des patients atteints de carcinome hépatocellulaire (HCC).
Selon Sam Whiting, M.D., Ph.D., cette désignation met en évidence le besoin criant de nouveaux traitements pour cette maladie complexe. Tempest envisage de procéder à une étude pivot de phase 3 pour amezalpat chez des patients HCC en première ligne.
Cette désignation suit des données positives d'une étude clinique mondiale randomisée de phase 1b/2 évaluant amezalpat plus l'atezolizumab et le bevacizumab standard par rapport à l'atezolizumab et au bevacizumab seuls, dans le traitement du HCC non résécable ou métastatique. Les résultats clés incluent :
- Une amélioration de six mois de la survie globale médiane (OS) avec un rapport de risques (HR) de 0,65 pour la thérapie combinée à l'amezalpat.
- Un taux de réponse objective (ORR) de 30% contre 13% pour le groupe témoin.
- Bénéfice de survie préservé dans des sous-populations clés, y compris les maladies négatives au PD-L1 et les maladies mutées au b-cathénine.
Ces résultats sont cohérents avec le mécanisme d'action d'amezalpat, ciblant à la fois les cellules tumorales et le système immunitaire du patient.
Tempest Therapeutics gab bekannt, dass die FDA die Waisenmedikamenten-Designation für amezalpat (TPST-1120) erteilt hat, ein orales, kleines Molekül und selektiver PPAR⍺-Antagonist zur Behandlung von Patienten mit hepatozellulärem Karzinom (HCC).
Laut Dr. Sam Whiting, M.D., Ph.D., unterstreicht diese Bezeichnung den dringenden Bedarf an neuen Behandlungen für diese herausfordernde Erkrankung. Tempest plant, eine entscheidende Phase-3-Studie für amezalpat bei HCC-Patienten in der Erstlinie durchzuführen.
Die Bezeichnung folgt positiven Daten aus einer globalen randomisierten Phase-1b/2-Studie, die amezalpat zusammen mit der Standardbehandlung mit Atezolizumab und Bevacizumab gegen Atezolizumab und Bevacizumab allein beim Treatment von nicht resezierbarem oder metastatischem HCC evaluierte. Zu den wichtigsten Ergebnissen gehören:
- Eine Verbesserung der medianen Gesamtüberlebenszeit (OS) um sechs Monate mit einem Hazard Ratio (HR) von 0,65 für die amezalpat-Kombinationstherapie.
- Eine objektive Ansprechrate (ORR) von 30% im Vergleich zu 13% für die Kontrollgruppe.
- Aufrechterhaltung des Überlebensvorteils in wichtigen Subpopulationen, einschließlich PD-L1-negativer Erkrankungen und b-Catenin-mutierten Erkrankungen.
Diese Ergebnisse sind konsistent mit dem Wirkmechanismus von amezalpat, der sowohl Tumorzellen als auch das Immunsystem des Patienten anvisiert.
- FDA Orphan Drug Designation granted for amezalpat (TPST-1120) to treat HCC.
- Six-month improvement in median overall survival (OS) with a hazard ratio (HR) of 0.65 for amezalpat combination therapy.
- Objective response rate (ORR) of 30% for amezalpat combination therapy versus 13% for standard care.
- Survival benefit preserved in key sub-populations, including PD-L1 negative and b-catenin mutated disease.
- None.
Insights
The FDA's Orphan Drug Designation for amezalpat represents a significant regulatory milestone for Tempest Therapeutics. This designation, granted for rare diseases affecting fewer than 200,000 people in the US, provides several key benefits including 7 years of market exclusivity, tax credits for clinical trials and potential fast-track designation.
The Phase 1b/2 trial results are particularly compelling:
- The 6-month improvement in median overall survival with a hazard ratio of
0.65 indicates a35 reduction in death risk - The objective response rate more than doubled from
13 to30 in the amezalpat combination arm - Efficacy in PD-L1 negative and b-catenin mutated populations addresses significant unmet needs
The dual mechanism targeting both tumor cells and immune system through PPAR⍺ antagonism represents a novel approach in HCC treatment, where current therapies have shown success. The alignment between FDA and EMA on the pivotal Phase 3 study pathway strengthens the global commercial potential.
For a micro-cap biotech with a market cap of
- Reduced development costs through tax credits for clinical trials
- Waived FDA user fees (worth several million dollars)
- 7-year market exclusivity upon approval
The strong efficacy data in first-line HCC positions amezalpat as a potential standard-of-care treatment in a market projected to reach
BRISBANE, Calif., Jan. 06, 2025 (GLOBE NEWSWIRE) -- Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-class1 targeted and immune-mediated therapeutics to fight cancer, today announced that the U.S. Food and Drug Administration (FDA) 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).
“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,” said Sam Whiting, M.D., Ph.D., chief medical officer and head of R&D of Tempest. “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 3 study for amezalpat in first-line HCC patients.”
This important regulatory designation follows positive data across multiple key study efficacy and safety endpoints in 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 and an objective response rate (ORR) of
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
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
The FDA's Orphan Drug Designation program provides orphan status to therapies intended for the treatment, diagnosis, or prevention of rare diseases that affect fewer than 200,000 people in the United States. This designation provides certain benefits, including tax credits for qualified clinical testing, waiver or partial payment of FDA application fees and seven years of market exclusivity, if approved.
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.
Forward-Looking Statements
This press release contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended (the “Securities Act”)) concerning Tempest Therapeutics, Inc. These statements may discuss goals, intentions, and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the management of Tempest Therapeutics, as well as assumptions made by, and information currently available to, management of Tempest Therapeutics. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “could”, “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions. All statements that are not historical facts are forward-looking statements, including any statements regarding: the design, initiation, progress, timing, scope and results of clinical trials, including the anticipated Phase 3 study for amezalpat; anticipated therapeutic benefit and regulatory development of the Company’s product candidates the Company’s ability to advance into a late-stage clinical company; and the Company’s ability to achieve its operational plans. Forward-looking statements are based on information available to Tempest Therapeutics as of the date hereof and are not guarantees of future performance. Any factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; and unexpected litigation or other disputes. Other factors that may cause actual results to differ from those expressed or implied are discussed in greater detail in the “Risk Factors” section of the Company’s Quarterly Report on Form 10-Q filed for the quarter ended September 30, 2024 and other documents filed by the Company from time to time with the Securities and Exchange Commission. Except as required by applicable law, Tempest Therapeutics undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. These forward-looking statements should not be relied upon as representing Tempest Therapeutics’ views as of any date subsequent to the date of this press release and should not be relied upon as prediction of future events. In light of the foregoing, investors are urged not to rely on any forward-looking statement in reaching any conclusion or making any investment decision about any securities of Tempest Therapeutics.
Investor & Media Contacts:
Sylvia Wheeler
Wheelhouse Life Science Advisors
swheeler@wheelhouselsa.com
Aljanae Reynolds
Wheelhouse Life Science Advisors
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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.
FAQ
What is the significance of the FDA Orphan Drug Designation for TPST-1120?
What were the key outcomes of the Phase 1b/2 clinical study for TPST-1120?
How does TPST-1120 impact sub-populations in HCC treatment?
What are the next steps for Tempest regarding TPST-1120?
What is the objective response rate (ORR) for TPST-1120 in the clinical study?
