A drug delivery platform developed by Monash University researchers in collaboration with PureTech Health plc has reached an important milestone, demonstrating for the first time in humans that a drug that is currently to be injected by degradation in the liver after oral administration , can 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 should be administered as a 60-hour intravenous infusion, a method that has inherent limitations, Monash University said. in a statement.
Current research, Monash said, suggests that PPD affects up to one in five new mothers, yet readily available medications to treat PPD specifically are limited, and an unsatisfied clinical need remains.
The ongoing Phase 1 clinical study of LYT-300 showed that when administered orally through the new technology for drug delivery ‘Glyph’, systemic blood levels were approximately nine times greater than those of orally administered allopregnanolone, based on previously published data. has the potential to dramatically increase its practicality and usefulness.
In the PureTech study, healthy healthy adults were given LYT-300 with the equivalent of 53 mg allopregnanolone, achieving plasma exposure levels with an AUCinf of 352 ng * hr / ml. This compares with a previously published study in solid healthy adults where 30 mg allopregnanolone was dosed orally, 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 on lipid uptake pathways, focused on the uptake of drugs into the lymphatic system and away from the liver.This gives 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 biotherapeutic company dedicated to the discovery, development and commercialization of highly differentiated drugs for devastating diseases.”
Porter said this is an important milestone for Glyph. These data show that allopregnanolone can be administered orally successfully, 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, which benefit can of an oral form of allopregnanolone.
“Because Glyph mediates drug transport through the lymphatic system, it has the potential to improve the bioavailability of orally administered drugs such as allopregnanolone. In addition, because it selects selective therapeutics in the lymphatic system, it has the potential to target therapies immune system.We hope that LYT-300 will be the first of many applications for Glyph.
Chief Medical Officer of PureTech Julie Krop, MD said: “Natural allopregnanolone has been shown to be effective in treating PPD and other neuropsychological conditions, but has so far required IV delivery due to high first pass liver metabolism. LYT-300 is designed to validated pharmacology of natural allopregnanolone with a potential oral treatment option for PPD and a variety of other neurological and neuropsychological conditions.
The LYT-300 Multiple Phase 1 program has three primary objectives – to demonstrate oral bioavailability, to evaluate safety and tolerability across a variety of doses, and to identify a dose to take forward. With the achievement of the first goal, additional exploration of doses and the effect of food on oral uptake of the prodrug progress, and assessments of safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) are measured. Dose escalation continues because 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.
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Monash tech in PPD drug delivery milestone
Source link Monash tech in PPD drug delivery milestone