After encouraging results from Phase 2 trials, PharmAust is now getting ready for a Phase 3 trial of its lead drug monepantel on the way to potential commercialisation.

Clinical stage biotech company, PharmAust (ASX:PAA), is one step closer towards commercialising its lead drug, monepantel (MPL), for canine cancer.

The company has just announced preparation for a Phase 3 trial for MPL in dogs with B-cell lymphoma, following encouraging results in the Phase 2 study.

Data from the Phase 2 trial has shown that combining MPL with prednisolone more than doubles the life expectancy of pet dogs, compared with standard-of-care (prednisolone alone).

And with the current price of canine chemotherapy being prohibitively expensive,  PharmAust believes that subject to Phase 3 results, MPL could be a commercially compelling alternative treatment.

“We’ve made clear progress in a short timeframe to better understand the monepantel and B-cell lymphoma dose response relationship, and now have a clearer understanding of the effective plasma range required for monepantel as a mono-therapy,” commented trial principal investigator, Kim Agnew.


Results from the Phase 2 studies

To date, 24 pet dogs with treatment resistant B-cell lymphoma have qualified for evaluation across the two trial programs.

A further two pet dogs were admitted to the trial, but were not evaluated due to incorrect dosing.

During the course of those trials, pet dogs were administered MPL as gelatin encapsulated liquid, or as a tablet.

MPL tablets were administered at four doses, and based on this, PharmAust has calculated an optimum drug plasma range for anticancer activity that would result in minimal side effects.

Of the seven pet dogs with drug plasma levels in the optimum range, six achieved stable disease progression, and one had a partial response with some tumours even completely disappearing.

Side effects observed were minimal or not detected, and include minor things such as occasional weight loss.

Of the six pet dogs that achieved stable disease progression, five continued to take MPL after the trial in combination with prednisolone.

To date, these five dogs have achieved much higher than expected mean and median survival times, at 125 and 138 days, respectively.

This 138-day median survival compares favourably with a recently reported 60-day median survival for similar pet dogs treated only with standard-of-care prednisolone.

All pet dog owners also reported very high quality of life for their pet dogs while taking MPL, with a testimonial page posted on the PAA website.

In comparison, the most common side effects of a dog being treated with chemotherapy include gastrointestinal effects (vomiting, diarrhea, or loss of appetite) and decreases in blood cell counts. Also, during chemotherapy, owners need to take precautions when handling their pet’s waste. Drugs may be excreted in the urine and faeces, so its not advisable for children to play with their pets.

“The trial data are becoming more interesting,” said PharmAust’s chief scientific officer, Dr Richard Mollard.

“Although this analysis examining the effects of combination with prednisolone is retrospective in nature, it enables the making of robust hypotheses and provides justification for their formal testing in Phase 3 studies.”

Dr Mollard said quality of life may be the most important outcome for pet dogs, as we don’t know how pet dogs balance expectations of their quality of life with expectations of quantity of life.

He said that extended overall survival time with good quality of life is the most important outcome for pet owners and veterinarians.

“PharmAust is pleased to proceed with development of monepantel while aiming to satisfy both of these outcome measures,” Dr Mollard added.

The company has now begun planning an extension of study sites outside of Australia to explore these findings in more detail – with sites in NZ and the US already chosen as potential options to broaden the upcoming enrolments for Phase 3.


Other cancer applications for MPL

PharmAust and its team of vets are confident that MPL’s ability to target a central metabolic pathway associated with tumour growth means that it will have applications in other canine cancers.

The company has already been approached by animal healthcare companies in the US and Germany for discussions.

Apart from pets, PharmAust is also working with clinical oncology units in Italy and the United Kingdom to evaluate the company’s new MPL tablet in a Phase II trial in humans, and to discuss the optimal type of cancers to target.

The company is also fighting against the COVID-19 disease, announcing in July that three independent laboratories have finished examining the effects of MPL and metabolite monepantel sulfone (MPLS) on SARS-CoV2 infection, which is the causal agent of COVID-19 disease.

In addition, a Phase I/II clinical trial on MPL for human patients with motor neurone diseases (MND) is set to commence in Q1 2022.

That study will look specifically into patients with Amyotrophic Lateral Sclerosis/Motor Neurone Disease (ALS/MND), and is expected to be supported by a $900k grant from the AFL-linked charity, FightMND (yet to be received).

This article was developed in collaboration with PharmAust, a Stockhead advertiser at the time of publishing.

This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.