Antev Ltd., a late clinical-stage biotech company developing a novel gonadotrophin-releasing hormone antagonist, Teverelix trifluoroacetate, announces that the US Food & Drug Administration has provided written guidance on the company’s proposed Phase 3 pivotal trial design.
- Phase 3 aims to demonstrate cardiovascular benefit of Teverelix versus GnRH agonists.
- Up to 30% of advanced prostate cancer patients on Androgen Deprivation Therapy have pre-existing Cardiovascular Disease.
- Phase 3 top-line results expected in 2027.
LONDON, March 08, 2023 (GLOBE NEWSWIRE) -- Antev Ltd., a late clinical-stage biotech company developing a novel gonadotrophin-releasing hormone (GnRH) antagonist, Teverelix trifluoroacetate (Teverelix), announces that the US Food & Drug Administration (FDA) has provided written guidance on the company’s proposed Phase 3 pivotal trial design. This would be the first Phase 3 trial for a specific label to treat prostate cancer in patients with increased cardiovascular risk, addressing a significant need for prostate cancer drugs with a better cardiac toxicity profile.
Prostate cancer is the second most common cause of cancer death in men[1], with around 5 million men living with the disease in the US and Europe. Current treatments using GnRH agonists have been shown[2] to have between two and four times increased risk of cardiovascular events in patients with a medical history of cardiovascular disease than antagonist treatments, a conclusion supported by the American Heart Association in a 2021 scientific statement[3][4]. Prior to initiating androgen deprivation therapy (ADT), a common form of hormone therapy, an estimated 30% of men have known cardiovascular disease (CVD)[5]. Teverelix, a decapeptide, has the potential to be the first hormone therapy specifically approved to treat advanced prostate cancer patients with a history of cardiovascular disease.
“We are delighted to reach this critical milestone in Antev’s journey to secure regulatory guidance to develop Teverelix in advanced prostate cancer patients with increased cardiovascular risk,” commented Amit Kohli, Chief Executive Officer of Antev. “This written acceptance by the US FDA on our proposed Phase 3 pivotal trial design provides great visibility and supports the company’s clinical plans for our innovative treatment that could combine profound castration, improved tolerability, and significantly reduced cardiovascular risk compared to GnRH agonists, which generate over US$ 3 billion in annual sales globally. Cardio-oncology is an important new therapeutic area, and Antev is leading the way to deliver improved patient and payor outcomes.”
Antev’s Chief Medical Officer, Dr Steve van Os, added, “Having worked on the global development and registration of Xtandi® for late-stage prostate cancer patients, I am very satisfied with the progress we are making at Antev in developing a novel GnRH antagonist that could help the many earlier-stage prostate cancer patients with an increased cardiovascular risk. With cardiovascular diseases being now the leading cause of death in men with prostate cancer and with up to 30% of prostate cancer patients having a history of CVD, there is a clear and urgent need for safer therapies that treat prostate cancer, yet do not increase cardiovascular risk.”
Antev’s Scientific Adviser, Dr Neal Shore MD FACS, CMO of Surgery and Oncology at GenesisCare USA, said, “There is an unmet medical need for a new specific ‘cardio-oncology’ indication for androgen deprivation therapy which will effectively treat the patient’s cancer while not worsening cardiovascular safety. This proposed Phase 3 trial is designed to provide the level one evidence that this GnRH antagonist could be the treatment of choice for prostate cancer patients with cardiovascular risks.”
Both GnRH agonists and antagonists are approved for the treatment of prostate cancer and although both bind to the same therapeutic target, the GnRH receptor in the pituitary gland, they have distinct mechanisms of action. While the GnRH agonist stimulates the GnRH receptor, leading to overexpression of Follicle Stimulating Hormone and Luteinizing Hormone, which in turn leads to an initial increase in the production of testosterone but then rapidly inhibited through a negative feedback loop, the GnRH antagonists directly suppress the production of sex hormones by competitively blocking the GnRH receptors at the pituitary gland, and thus do not create a testosterone surge.
Antev’s proposed ANT-1111-04 is a global Phase 3 trial in up to 1,500 advanced prostate cancer patients with increased CV risk with a 1:1 randomization against standard of care (GnRH agonist) that aims to read out by 2027.
References
1 – Bray et al. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), pp.394-424
2 – Studies by Margel et al. in 2019 (n=80) and Shore et al. 2020 (n=930).
https://pubmed.ncbi.nlm.nih.gov/32469183/
3 – AAH Scientific Statement, published in Genomic and Precision Medicine (Vol 14, No. 3. 26 April 2021) “Impact of Hormonal Therapies for Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart” Association https://www.ahajournals.org/doi/10.1161/HCG.0000000000000082
4 – Accompanying AAH press release: https://newsroom.heart.org/news/close-monitoring-for-heart-risk-needed-if-breast-prostate-cancer-treatment-includes-hormones
5 – PCN194 Prevalence of Major Adverse Cardiac Events (MACE) in Patients with Prostate Cancer (PC) Receiving Androgen Deprivation Therapy (ADT) in the United States: https://www.valueinhealthjournal.com/article/S1098-3015(20)32587-0/fulltext
For more information, please contact:
Antev Limited
Amit Kohli, CEO
Email: amitkohli@antev.co.uk
Scius Communications
Katja Stout
+44 778 943 5990
katja@sciuscommunications.com
Daniel Gooch
+44 774 787 5479
daniel@sciuscommunications.com
About Teverelix and GnRH antagonists
Teverelix is an injectable, long-acting GnRH antagonist. In a novel and unique microcrystal formulation which can overcome the well documented safety issues associated with other GnRH antagonist candidates in the treatment of prostate cancer. With good injection site tolerance and a six-week dosing interval, Teverelix is likely to secure better patient compliance and therefore better clinical outcomes. Teverelix also has the potential to be developed for BPH (Benign Prostate Hyperplasia), AUR (Acute Urinary Retention), Endometriosis and Uterine Fibroids.
About Antev Limited
Antev Limited, based in London, is a late clinical-stage biopharmaceutical company, focused on the development of a robust registration-ready data package for the treatment of advanced prostate cancer in patients with high cardiovascular risk.
Prostate cancer affects an estimated 1.3 million new patients annually around the globe and is the second most common cause of cancer death in men. Gonadotrophin-releasing hormone (GnRH) agonists and antagonists represent the foundation of prostate cancer treatment.
The Company acquired the intellectual property rights for the decapeptide Teverelix, a novel GnRH antagonist, from LifeArc, one of the UK’s leading medical research charities. Teverelix is formulated as a teverelix TFA salt. It forms a microcrystalline suspension at the concentration used for injection, allowing a small injection volume. This very rare property allows for a highly injectable drug product that exhibits a sustained release.
Antev is backed by private investors and was founded in 2013. For more details see our website and follow us on LinkedIn.
