PharmAust makes progress towards next clinical trial of monepantel

Oncology company PharmAust (ASX: PAA) came out of a trading halt this morning with news that its monepantel canine trial achieved a “successful outcome” with phase 3 trials already on the horizon.

The trial is currently on hold pending an interim report for development partner Elanco US, following instances of dogs experiencing elevated liver enzymes and inappetence at high dosage levels.

In a statement to the market, the company said its latest trial provided a “meaningful trend” and compared favourably to a previous trial of a liquid version of monepantel in 2017.

Most notably, the company declared the trial had met all primary goals including determining the safety and efficacy of monepantel tablets, evaluating drug delivery capabilities of newly developed monepantel tablets in dogs with cancer, producing sufficient data to enable further discussions with Elanco US, and, possibly most significant, deriving sufficient data to enter phase 3 trials.

A total of six dogs were given monepantel as part of a 28-day treatment program administered at home.

Of the dogs that completed the assessment, one dog achieved a partial response with a greater than 60% reduction in total tumour burden and one lymph node tumour regressing completely. Meanwhile, four dogs achieved stable disease and one dog had progressive disease at the end of the trial.

Alongside the results published today, PharmAust said that from the plasma monepantel levels recorded during the trial, all dogs reached levels up to 50 times higher than those recorded in the human trial undertaken at the Royal Adelaide Hospital in 2014/2015.

“Some variability was observed in plasma levels and, unexpectedly, at the lower blood levels of monepantel there were better outcomes. This observation may be consistent with the mechanism of action of mTOR inhibitors and lends itself to reducing and optimising the future dosing of monepantel tablets,” the company said.

Notably, trial results indicated an unexpected outcome relating to dosage.

According to PharmAust, due to the high dosing levels being used, some pet dogs developed inappetence and weight loss.

As a result, pet owners reported difficulties in administering tablets, which means reducing the target dose in future trials could likely result in better outcomes in terms of efficacy, safety and dosing pets.

Betting on monepantel

PharmAust’s lead drug candidate, monepantel, is an inhibitor of the mTOR pathway – considered to be a key driver of cancer.

Monepantel has already been evaluated in phase 1 clinical trials in humans and dogs and was well tolerated and produced a significant reduction in key prognostic biomarkers.

“Monepantel appears to be showing anti-cancer activity in dogs with lymphoma and I believe that controlled phase 3 trials are now warranted to investigate the efficacy and safety of lower dose monepantel,” said Dr Claire Cannon from the University of Melbourne and U-Vet Werribee animal hospital.

“The phase 2 trial results suggest that monepantel, perhaps in combination with standard of care lymphoma therapy, may represent a future prospect for treatment of dogs with this disease,” she said.

According to PharmAust, it is now “uniquely positioned” to commercialise monepantel for treatment of human and veterinary cancers as it advances the drug in phase 2 clinical trials.

“Having the monepantel tablets achieve a 60% reduction in tumour burden in one dog, with one lymph node returning to normal, is a terrific and unexpected outcome. The correlation of lower MPL blood levels with superior outcomes is also a very positive trend, providing flexibility for better outcomes in a future phase 3 trial,” said PharmAust’s chief scientific officer Dr Richard Mollard.