FDA Receives NDA for 3-Month Version of Leuprolide Mesylate for Advanced Prostate Cancer

A 502(b)(2) new drug application (NDA) seeking the approval of a ready-to-use, 3-month depot formulation of leuprolide mesylate (Camcevi) for the palliative treatment of patients with advanced prostate cancer has been submitted to the FDA.¹

The NDA is supported by data from an open-label, single-arm phase 3 trial (NCT03261999), which demonstrated that a suppression of serum testosterone of no more than 50 ng/dL by day 28 and from days 28 to 168 was achieved by 97.9% (95% CI, 93.5%-99.3%) of patients treated with leuprolide mesylate in the intention-to-treat population (n = 144).²

At day 28, the mean testosterone concentration was 17.8 ng/dL, and the suppression rate was 98.6% in evaluable patients (n = 143). Following the second injection of leuprolide mesylate, no mean increase in testosterone was observed. Among the 3 patients who did not meet the primary end point, 2 did not achieve the required castration level on day 28, and 1 patient experienced transient testosterone escape following the second injection.

In May 2021, the FDA approved a 6-month subcutaneous depot formulation of leuprolide mesylate as a ready-to-use treatment for patients with advanced prostate cancer.³

"Following the successful launch of [the leuprolide mesylate] 6-month depot formulation in 2022, we are excited to announce the submission of the 3-month version of [leuprolide mesylate] NDA to the US FDA. This marks a significant milestone in our efforts to expand treatment options for patients with advanced prostate cancer,” Ben Chien, PhD, founder and chairman of Foresee Pharmaceuticals, stated in a news release.¹ “We look forward to the regulatory approval from the FDA in 2025, and commercial launch in 2026, providing patients with its differentiated ready-to-use profile.”

The phase 3 trial enrolled patients at least 18 years of age with histologically confirmed carcinoma of the prostate who were deemed candidates for androgen ablation therapy.⁴ Patients were required to have a baseline serum testosterone level of more than 150 ng/dL, an ECOG performance status of 0 to 2, a life expectancy of at least 18 months, and adequate laboratory values.

Treatment with chemotherapy, immunotherapy, cryotherapy, radiotherapy, or anti- androgen therapy concomitantly or within 8 weeks of screening was not allowed; however, radiation for pain control was allowed during the study. Other key exclusion criteria consisted of any vaccine within 4 weeks of screening; a history of blood donation within 2 months of screening; a history of anaphylaxis with any LH-RH analogues; treatment with any LH-RH suppressive therapy within 6 months of screening; and any major surgery within 4 weeks of screening.

All patients received leuprolide mesylate at 25 mg on day 0, followed by a second dose on day 84. Patients were followed until day 168.

Along with the primary end point of serum testosterone suppression from days 28 to 168, safety served as the trial’s secondary end point.

Regarding safety, 90 patients experienced a total of 217 treatment-emergent adverse effects (TEAEs). Specifically, 165 TEAEs in 79 patients were grade 1, and 43 TEAEs in 28 patients were grade 2. Nine severe TEAEs occurred in 7 patients.²

The most common AEs reported in more than 5% of patients included hot flushing (24.31%), hypertension (11.11%), increased body weight (7.64%), and injection site hemorrhage (5.56%).

References

1. Foresee Pharmaceuticals announces submission of the NDA to the U.S. FDA for the 3-month version of Camcevi for the treatment of advanced prostate cancer. News release. Foresee Pharmaceuticals. October 30, 2024. Accessed October 30, 2024. https://www.foreseepharma.com/en-us/news/1/362
2. Foresee Pharmaceuticals announces successful topline results from phase 3 registration study of LMIS 25 mg in prostate cancer. News release. Foresee Pharmaceuticals. February 21, 2019. Accessed October 30, 2024. https://www.prnewswire.com/news-releases/foresee-pharmaceuticals-announces-successful-topline-results-from-phase-3-registration-study-of-lmis-25-mg-in-prostate-cancer-300799580.html
3. Foresee Pharmaceuticals announces FDA approval of CAMCEVI for the treatment of advanced prostate cancer; Accord BioPharma to head the US commercialization. News release. Foresee Pharmaceuticals. May 26, 2021. Accessed October 30, 2024. https://www.foreseepharma.com/en-us/news/1/340
4. Safety, efficacy, and pharmacokinetic behavior of leuprolide mesylate (LMIS 25 mg) in subjects with prostate cancer. ClinicalTrials.gov. Updated May 4, 2020. Accessed October 30, 2024. https://clinicaltrials.gov/study/NCT03261999