Monash tech in PPD drug delivery milestone

A drug delivery platform developed by Monash University researchers in partnership with PureTech Health plc has reached a significant milestone, showing for the first time in humans that a drug that currently must be injected due to breakdown in the liver after oral administration, may be administered as a simple oral capsule.

The data were generated with ‘LYT-300’, an oral form of allopregnanolone. Allopregnanolone is currently the only FDA-approved medication on the market specifically for the treatment of postpartum depression (PPD), however it must be administered as a 60-hour intravenous infusion, a method that has inherent limitations, said Monash University in a statement.

Current research, Monash stated, suggests that PPD affects up to one in five new mums, yet readily accessible medications to specifically treat PPD are limited, and an unmet clinical need remains.

“The ongoing Phase 1 clinical study of LYT-300 showed that when orally administered via the new drug delivery technology ‘Glyph’, systemic blood levels were approximately ninefold greater than that of orally administered allopregnanolone, based on previously published data. This has the potential to dramatically increase practicality and usability.

“In the PureTech study, fasted healthy adults were given LYT-300 containing the equivalent of 53 mg of allopregnanolone, achieving plasma exposure levels with an AUCinf of 352 ng*hr/mL. This compares to a previously published study in fasted healthy adults where 30 mg of allopregnanolone was orally dosed, resulting in an AUCinf of 21 ng*hr/mL.

“This is the first clinical validation of the Glyph technology in humans. The platform, developed by Professor Chris Porter and his team at the Monash Institute of Pharmaceutical Sciences, piggybacks onto lipid absorption pathways, targeting drug absorption to the lymphatic system and away from the liver. This provides patients an opportunity to switch from invasive intravenous administration to a simple oral capsule.

“The Glyph technology is licensed to commercial partner PureTech Health plc, a clinical-stage biotherapeutics company dedicated to discovering, developing and commercialising highly differentiated medicines for devastating diseases.”

Porter said that this is a key milestone for Glyph. “These data show that allopregnanolone can be successfully administered orally, which is very encouraging not only for women with PPD, but also for those with other neurological and neuropsychiatric conditions, including other forms of depression, anxiety and sleep disorders, who could benefit from an oral form of allopregnanolone.

“Because Glyph re-routes drug transport via the lymphatic system, it has the potential to enhance the bioavailability of orally administered drugs like allopregnanolone. In addition, since it selectively traffics therapeutics into the lymphatic system, it has the potential to target therapies to the immune system. We are hopeful that LYT-300 will be the first of many applications for Glyph.”

Chief Medical Officer of PureTech Julie Krop, MD said: “Natural allopregnanolone has demonstrated efficacy for the treatment of PPD and other neuropsychological conditions, but up to now has required IV delivery due to high first pass liver metabolism. LYT-300 is designed to unlock the validated pharmacology of natural allopregnanolone with a potential oral treatment option for PPD and a range of other neurological and neuropsychological conditions.”

The multi-part Phase 1 program of LYT-300 has three primary objectives — to demonstrate oral bioavailability, evaluate safety and tolerability across a range of doses, and to identify a dose to take forward. With the achievement of the first objective, additional dose exploration and the effect of food on oral absorption of the prodrug are progressing, and assessments of safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) will be measured. Dose escalation continues as no dose-limiting toxicities have been observed to date. The full results of the Phase 1 study will be shared in a future scientific forum.

In addition to Porter, the team at Monash that developed the Glyph technology was led by Associate Professor Natalie Trevaskis and Dr Sifei Han, and included Dr Luojuan Hu, Dr Dan Zheng, Dr Nathania Leong, Dr Garima Sharma and Dr Mitchell McInerney.

Image credit: ©stock.adobe.com/au/Rasi