Antev Receives US FDA Guidance on Teverelix® Phase 3 Trial Design for Treating Advanced Prostate Cancer Patients with Increased Cardiovascular Risk

Antev Receives US FDA Guidance on Teverelix® Phase 3 Trial Design for Treating Advanced Prostate Cancer Patients with Increased Cardiovascular Risk

·     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, UK, 9 March 2023: 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://ic-os.org/wp-content/uploads/2020/04/2019-CV-morbidity-in-a-RCT-comparing-GnRH-agonist-and-GnRH-antagonist.pdf

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:

Amit Kohli, CEO
Antev Limited
Email: amitkohli@antev.co.uk