4. Discussion
death, non-cancer, Prostate cancer, deaths, prostate cancer
CARDIOVASCULAR DISEASE, DISEASE, PROSTATE CANCER, INJECTION SITE REACTION, INJECTION SITE INDURATION, PROSTATE CANCER
Prostate cancer is the second most common cause of cancer-related deaths in men, representing a major source of morbidity and mortality. Androgen deprivation therapy (ADT) is the primary treatment for patients with advanced prostate cancer at disease presentation, which can be achieved either with surgical or chemical castration [In the United States, cardiovascular disease is the main cause of death for prostate cancer patients, and patients with prostate cancer have a higher risk of death from non-cancer causes than the general population [While the Phase 2 trials reported in this paper were first conducted several years ago, little progress has been made during that time in terms of injectable GnRH antagonists. Since degarelix was approved in 2008, there have been no new injectable GnRH antagonists. Data from mouse model studies suggest that the increased CV risk with GnRH agonists compared to GnRH antagonists may be attributable to FSH levels coupled with T-lymphocyte GnRH receptor activation [Therefore, the development of teverelix DP is still relevant and the development of teverelix DP is now continuing with a new sponsor with a focus on its CV safety compared to GnRH agonists and with the aim of an improved administration schedule (longer duration of action requiring fewer administrations) and local tolerability profile than degarelix.The data from these five Phase 2 clinical studies adds to the evidence from a Phase 1 clinical study that was conducted in older, healthy male subjects, showing that teverelix DP has a good safety profile and is well tolerated [The most commonly reported AE In the studies where teverelix DP is administered via SC administration was an injection site reaction, particularly injection site induration, generally of a mild intensity. In all trials, an injection site inspection was performed at every study visit post-administration (either as a formal safety endpoint in three trials or as part of analyzing AEs in two trials), and it was not up to the trial subjects to report any reactions experienced as was the case in the pivotal degarelix clinical trial [The effective loading doses of teverelix DP required injections to be administered on 3 consecutive days, which is inconvenient for the patients and may have implications for healthcare costs and resource utilization. Ideally, the loading dose would be administered at a single clinic visit, and data from this study have laid the foundations for such a regimen.An ongoing Phase 2B clinical trial (NCT04693507) with teverelix DP is testing initial loading doses of 120 mg SC plus 120 mg IM injections and 180 mg SC plus 180 mg IM injections—administered on Day 0—followed by maintenance doses of teverelix DP 120 mg SC or 180 mg SC at Day 42 and every 6 weeks up to Day 168. The establishment of an effective dosing regimen of teverelix DP in prostate cancer patients will facilitate the conduct of a Phase 3 trial in advanced prostate cancer patients at increased CV risk to test the potential CV superiority of teverelix DP versus leuprolide. The development of an ADT agent with improved CV safety will meet an unmet clinical need in this patient population.