Approval sought for testosterone undecanoate in Canada

Marius Pharmaceuticals has filed a new drug submission (NDS) with Health Canada for potential approval of testosterone undecanoate (Kyzatrex) CIII capsules, an oral testosterone replacement therapy (TRT) for the treatment of adult men with conditions associated with a deficiency or absence of endogenous testosterone, the company announced in a news release.¹

Testosterone undecanoate received US FDA approval in July 2022 for the treatment of male patients with hypogonadism.

A decision on the NDS is expected in Q2 of 2025. According to Marius, if approved, testosterone undecanoate could become the first approved oral testosterone therapy option available in Canada.

“We are excited by this first international filing and look forward to helping more patients by broadening the availability of oral testosterone. Our goal is to provide men worldwide with access to effective, convenient treatment options for testosterone deficiency,” said Nita Nimmons, director of quality and regulatory at Marius Pharmaceuticals, in the news release.¹ “Testosterone is a critical metabolic hormone that is crucial for many functions in the body. We hope that by increasing access to KYZATREX, we can become part of a solution to what has become a worldwide men’s health crisis.”

Testosterone undecanoate received US FDA approval in July 2022 for the treatment of male patients with hypogonadism. The approval was supported by safety and efficacy data from the phase 3 MRS-TU-2019EXT trial (NCT04467697), for which results were recently published in the journal Therapeutic Advances in Urology.²

The MRS-TU-2019EXT trial was conducted as a 6-month extension study of the phase 3 MRS-TU-2019 trial (NCT03198728), which assessed testosterone undecanoate vs a control arm in men with hypogonadism.

Overall, data from the extension study showed that 87.8% of treated patients (worse-case scenario calculations) and 96.1% of patients who completed the study (n = 127) achieved eugonadal mean plasma testosterone values (222 to 800 ng/dL) over 24 hours at 90-day follow-up. Further, mean levels of free testosterone increased from 7.0 ng/dL to 14.1 ng/dL after 90 days of treatment.

The average serum testosterone was 452 ng/dL at 90 days, and maximum testosterone concentrations all met the FDA criteria for TRT. Eugonadal percentages were comparable for all patients regardless of age, weight, or body mass index, with diet showing no effect on percentages.

The investigators also found decreases in follicle-stimulating hormone and luteinizing hormone after 90 and 180 days of treatment, although levels did not reach 0 at either of the 2 post-baseline assessments. Additionally, the 24-hour mean change in systolic ambulatory blood pressure was 1.7 mmHg (95% CI, 0.3-3.1) after 120 days of treatment. After 190 days of treatment, systolic blood pressure (SBP) appeared stable, with a mean increase of 1.8 mmHg (95% CI, 0.3-3.2).

Regarding safety, 37.4% of patients experienced a treatment-emergent adverse event (TEAE). All TEAEs were of mild to moderate intensity, and no serious TEAEs were reported. Hypertension was the only drug-related AE observed in more than 2% of patients. By day 180, 87.1% (n = 135) of participants had completed the study. The primary reasons for study discontinuation were withdrawal (5.8%), lost to follow-up (3.9%), and other (2.6%).

In total, the 6-month, open-label, multicenter MRS-TU-2019EXT study enrolled 155 men with hypogonadism, with 139 of those men included in the efficacy population. Patients were either newly recruited or previously enrolled in the MRS-TU-2019 trial. For the start of the study, participants first received 200 mg testosterone undecanoate twice daily with meals. Doses of the therapy were titrated over 2 28-day cycles between 100 and 800 mg daily.

The primary efficacy end points were the percentage of patients with a mean plasma total testosterone concentration over 24 hours within the normal range of 222 ng/dL to 800 ng/dL on the final pharmacokinetic visit at day 90 of the study, as well as the change from baseline in the 24-hour mean SBP, as measured by ambulatory blood pressure monitoring after 120 days of treatment. Safety end points included the incidence of AEs, serious AEs, and AEs leading to study withdrawal during treatment.

References

1. Marius Pharmaceuticals submits KYZATREX (testosterone undecanoate) CIII capsules for approval to Health Canada. News release. Marius Pharmaceuticals LLC. July 30, 2024. Accessed July 31, 2024. https://www.globenewswire.com/en/news-release/2024/07/30/2921110/0/en/Marius-Pharmaceuticals-Submits-KYZATREX-Testosterone-Undecanoate-CIII-Capsules-for-Approval-to-Health-Canada.html

2. Bernstein JS, Dhingra OP. A phase III, single-arm, 6-month trial of a wide-dose range oral testosterone undecanoate product. Ther Adv Urol. 2024 Apr 10:16:17562872241241864. doi:10.1177/17562872241241864