PharmAust Limited’s (ASX: PAA) clinical trials testing anti-cancer drug monepantel in canine lymphoma has successfully achieved phase two primary endpoints with administering veterinarians now wanting to move to phase three.
The clinical stage biotech said the 15 pet dogs treated during the phase IIa and IIb studies demonstrated sufficient and statistically significant anti-cancer activity to continue development into this next phase.
The two interim primary endpoints were objective tumour regression and increased progression-free survival. Data from the trials will also help define the optimised tolerated dosage for the phase three study.
PharmAust chief scientific officer Dr Richard Mollard said he is confident the interim data indicates meaningful clinical outcomes and the company’s aim now is to translate that data into commercially valuable outcomes.
“Many of the pet owners relished the improved quality of life of their dogs on trial. We now wish to formally test this increased quality of life following monepantel treatment during the next stages and as a comparator with alternative treatments such as prednisolone,” he said.
Successful anti-cancer esults
PharmAust’s study has been focused on using monepantel to treat multi-centric high-grade B-cell lymphomas, which is considered one of the more aggressive cancers to study in canine oncology.
The phase two study found objective regression in one of the first eight dogs, with some tumours resolving completely. In addition, objective stable disease or better occurred in six of the first 15 dogs treated over the 28-day trial period. PharmAust described this as a “compelling outcome”.
Three of the pet dogs with advanced disease that were treated with lower dose monepantel were withdrawn before completing the 28-day trial period due to disease progression.
However, PharmAust cited published mean and medium times for untreated dogs showing that normally, eight of the 15 dogs would have been euthanised by day 29 or 30 with aggressively progressive disease and poor quality of life.
The company reported that following the trial, at least six of the dogs continued with either monepantel alone or in combination with prednisolone (a steroid medication typically used in cancer treatment).
PharmAust adopted a Bayesian method of statistical inference that was approved before the start of trials by pharmaceutical representatives, four independent Australian ethics committees and seven independent practicing veterinarians.
“In addition to the standard measurements of target superficial lymph nodes that are characteristic of many such trials, we incorporated comprehensive thoracic X-ray and abdominal ultrasound analyses into the trial design,” Dr Mollard said.
“This means that designation of stable disease in this trial really means comprehensive stable disease, not superficially stable disease as per many other trials where progression might be hidden somewhere else in the body,” Dr Mollard added.
Implications for human cancer therapy
PharmAust said not only does the phase IIb trial open the door for the company to explore the value of monepantel in other canine cancers, it also establishes a therapeutic window for clinical trials in human cancers.
“Achieving stable disease in primary cancerous lesions as well as in metastatic disease could have substantial value in human cancer therapy particularly if progression-free survival correlates with overall survival,” the company said, noting that stable disease was observed in a previous small phase one trial in humans.
PharmAust now intends to contact leading global pharmaceutical companies to seek partners to co-develop and commercialise monepantel for the treatment of veterinary cancers.
It said animal healthcare companies in the United States and Germany have already approached the company for discussions.
Dr Mollard said normally PharmAust would continue with an extension of the phase two Bayesian approach by continuing to treat up to 46 dogs according to the full phase two design.
However, he said advice from the administering veterinarians is to instead immediately commence preparations for phase three, in which PharmAust will fine tune the optimal dose of monepantel.
PharmAust principal investigator Dr Kim Agnew added that the “very complete” individual patient outcomes of phase two indicate that monepantel can positively impact the lives of canine patients with B-cell lymphoma.
“Phase three studies enable a deeper investigation of how monepantel can best become part of a canine oncologist’s therapeutic portfolio. This will be a very exciting part of the development,” he said.