FDA approval sought for novel oral testosterone replacement therapy for hypogonadism

Marius Pharmaceuticals has submitted a new drug application (NDA) to the FDA 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 based on a pivotal phase 3 trial, the results of which have not yet been made available. Marius intends to share the data at medical meetings this year.

“Submission of our first NDA is an important milestone, which is the culmination of over a decade of meticulous research and dedication and is just the beginning for Marius, as our pipeline will continue to advance research and development in this important therapeutic area that has a multitude of effects on our health system,” Himanshu H. Shah, founder and executive chairman of Marius, stated in a press release.

The pivotal study is officially known as, “A 6 Month, Open Label, Ambulatory Blood Pressure Monitoring (ABPM) Extension Study,” (MRS-TU-2019EXT; NCT04467697).² It is an extension of the phase 3 MRS-TU-2019 study (NCT03198728).

Key inclusion criteria for MRS-TU-2019EXT included:

• 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 MRS-TU-2019EXT included:

• 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 full lists of inclusion and exclusion criteria are available on the MRS-TU-2019EXT page on ClinicalTrials.gov.

All patients on the 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.

In its press release, Marius noted that more than 96% of patients enrolled in MRS-TU-2019EXT who completed 90 days of treatment reached average testosterone levels in the normal range.

Regarding safety, Marius reported that across phase 3 studies of SOV2012-F1, the most frequently reported treatment-related treatment-emergent adverse event (TEAE) was hypertension. There were no serious TEAEs related to SOV2012-F1 reported in the studies.

“We are extremely proud to have generated compelling efficacy and safety data in our Phase 3 trials,” Om Dhingra, PhD, co-founder and CEO of Marius, stated in the press release. “We look forward to continuing to work collaboratively with the FDA on the review of our application, and if approved, Kyzatrex has the potential to become the standard of care for the treatment of primary and secondary hypogonadism globally.”

References

1. Marius Pharmaceuticals Submits New Drug Application to U.S. FDA for Next-Generation Oral Testosterone Replacement Therapy in Male Patients With Hypogonadism. Posted January 5, 2021. https://bit.ly/3s6Y7UC. Accessed January 5, 2021.

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