FDA accepts application for novel testosterone replacement therapy for hypogonadism

The FDA has accepted a new drug application (NDA) for SOV2012-F1 (Kyzatrex), an oral testosterone undecanoate soft gelatin capsule, for the treatment of adult men with primary or secondary hypogonadism.¹

The NDA is supported by findings from the pivotal phase 3 ReTUNE trial (NCT03198728),² as well as a 6-month extension study of the ReTUNE trial (NCT04467697).³ Marius Pharmaceuticals, the manufacturer of SOV2012-F1, reported in a press release that more than 96% of patients in the pivotal phase 3 trial who completed 90 days of treatment reached average testosterone levels in the normal range.

Regarding safety, the most common treatment-emergent adverse event (TEAE) was hypertension, while there were no serious TEAEs deemed related to the study drug across the phase 3 trials.

Additional data from these trials have not yet been released, with Marius planning to share the results at medical meetings this year. Under the Prescription Drug User Fee Act, the FDA is scheduled to make a final decision on the NDA on or before October 31, 2021.

The multicenter, open-label ReTUNE study enrolled adult hypogonadal men. Patients were randomized to SOV2012-F1 or AndroGel, a topical testosterone gel.

Key inclusion criteria for ReTUNE were:

• Male aged 18-65 years with hypogonadism
• 1 or more clinical features consistent with male hypogonadism
• No prior androgen replacement therapy or adequate washout of prior androgen replacement therapies
• No ongoing testosterone treatment or willing to halt current testosterone treatment.

Key exclusion criteria for ReTUNE were:

• Serum PSA >2.5 ng/ml and/or abnormal prostate gland on palpation
• Oral, topical, intranasal, or buccal testosterone therapy in prior 2 weeks
• Intramuscular testosterone injection of short-acting duration in prior 4 weeks
• Intramuscular testosterone injection of long-acting duration in prior 20 weeks
• Testosterone implantable pellets in prior 6 months
• Drugs with the potential to distort assessment of serum androgen levels, such as 5 alpha-reductase inhibitors or drugs with antiandrogenic properties, had to be stopped ≥1 month before study enrollment.
• All over-the-counter products, such as food/herbal supplements, with the potential to impact testosterone levels had to cease ≥1 week before entering the study.

The study lasted 12 months, comprising a 3-month (90-day), open-label efficacy period and a 9-month period for safety evaluation. The primary outcome measure was the percentage of patients with average testosterone levels in the normal range after completing 90 days of treatment. The secondary end point was maximum plasma testosterone concentration.

The extension trial is officially known as, “A 6 Month, Open Label, Ambulatory Blood Pressure Monitoring (ABPM) Extension Study,” (MRS-TU-2019EXT).

All patients on the extension trial received a starting daily dose of SOV2012-F1 at 400 mg. The dosing was titrated up to a maximum level of 600 mg/day, based on plasma testosterone assessment following 14 and 42 days of therapy.

There were 2 primary end points. The first was the change from baseline in 24-hour average ambulatory systolic blood pressure following 120 days of receiving SOV2012-F1. The other primary end point was patient response to a lower initial dose of SOV2012-F1 with up and down titration.

References

1. Marius Pharmaceuticals Receives PDUFA Date for KYZATREX® NDA for Treatment of Hypogonadism. Published online March 11, 2021. Accessed March 11, 2021. https://bit.ly/2PUZCqh.

2. NIH ClinicalTrials.gov. Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men. Last updated July 13, 2020. Last updated January 15, 2021. Accessed March 11, 2021. https://clinicaltrials.gov/ct2/show/NCT04467697.

3. NIH ClinicalTrials.gov. Ambulatory Blood Pressure Monitoring (ABPM) Extension Study of Oral Testosterone Undecanoate in Hypogonadal Men. Last updated July 13, 2020. Accessed January 5, 2021. https://clinicaltrials.gov/ct2/show/NCT04467697.