Repurposed drug shows potential as leukaemia treatment

A drug developed at the University of Dundee for a neglected tropical disease could be repurposed to treat leukaemia following fast-track designation by the United States Food and Drug Administration (USFDA).

The drug, originally known as DDD86481 and now named PCLX-001, will be trialled in adult patients with relapsed or refractory Acute Myeloid Leukaemia (AML).

PCLX-001 was originally developed by Dundee’s drug discovery unit as part of a programme to treat African sleeping sickness. The compound is an analogue of DDD85646, which inhibited an essential function (myristoylation) in the parasite that causes sleeping sickness, but was not suitable to treat the latter stages of the disease that affect the brain.

During this research, the Dundee team discovered the compound could also kill some human cancer cells by the same process, but they could not identify which cancers were appropriate for clinical trials.

The entire family of related NMT-inhibiting compounds was then licensed by Canadian pharma company Pacylex Pharma, who are developing PCLX-001 as a once-a-day oral pill initially to treat leukaemia and lymphoma. It has also since been shown to inhibit the growth of lung and breast cancer tumours in animal models.

Professor David Gray, Head, Biology, Drug Discovery Unit, said, “Dr Luc Berthiaume, from the University of Alberta, had a deep understanding of cancers he believed such compounds could work against, but did not have the compounds to prove his theories.

“It was, therefore, serendipitous that Luc was introduced to PCLX-001, then known as DDD86481, at a subsequent conference he invited me to speak at. Everyone at the DDU is delighted to hear that PCLX-001 has received fast-track designation. This is another important step towards delivering real benefits to cancer patients.”

Pacylex is a clinical-stage company that was spun out of Dr Berthiaume’s lab and develops the first-in-class therapies for leukaemia, lymphoma and solid tumour cancers.

The FDA’s decision was informed by the results of Pacylex’s non-clinical studies and an ongoing phase-I/II clinical study of PCLX-001 in Non-Hodgkin Lymphoma (NHL) and solid tumour patients, which showed the treatment to have a favourable safety and tolerability profile.

The USFDA also recently approved PCLX-001 for phase-I clinical study to start in AML patients in the coming months and granted it Orphan Drug Designation (ODD). PCLX-001 is currently being studied in cancer patients at several research institutes in Canada and is the first and only NMT inhibitor in clinical studies. It is the fourth molecule developed at DDU to enter clinical trials.