FDA lifts second trial hold for Prescient’s lead drug, with one to go

Slowly but surely, Australia’s Prescient Therapeutics is getting its lead cancer program back on track, with two of three trials subject to an FDA clinical hold now cleared to resume.

The regulator put Prescient’s PTX-200 candidate on hold in May after a subject enrolled in the company’s breast cancer study developed liver failure and died, bringing three trials of the Akt inhibitor in breast and ovarian cancer and acute myeloid leukemia (AML) to a halt. The fatality involved a woman who was also taking paclitaxel, which is known to affect liver metabolism.

In September the FDA lifted the stay on the phase 1b/2 AML trial, and followed suit on the ovarian cancer study this month, after Prescient tweaked the risk-management protocols in the studies and agreed to carry out more liver function tests.

The phase 2 breast cancer trial remains on hold, but the Melbourne-based company is hopeful that it will be able to resume that shortly. It’s excited by the results seen with the drug to date, which have included a pathologic complete response (pCR) in one of eight patients enrolled in its phase 1b breast cancer trial.

Analysts at Edison estimate that the delay has held back the PTX-200 program by a year or so, putting a potential launch date back to 2024 from 2023, and any partnering deal back to 2020 rather than 2018. They put the chances of approval at around 15% at the moment, but with considerable sales potential—up to $2.4 billion—assuming the drug gets approved in all three target indications.

Akt (also known as PI3K) is a component of signaling pathways known to promote cancer cell growth and resistance to chemotherapy. Gilead’s Zydelig (idelalisib)—approved for chronic lymphocytic leukemia and two types of lymphoma—was the first drug targeting the pathway to reach the market but has been knocked back commercially by toxicity issues. In September Bayer’s PI3K inhibitor Aliqopa (copanlisib) got accelerated approval from the FDA for follicular lymphoma.

There are several other drugs targeting this pathway in clinical testing including drugs from Eli Lilly and Array NioPharma/Roche, although GlaxoSmithKline was forced to discontinue its Akt candidate afuresertib earlier this year.

With the PTX-200 program getting back on track, Prescient has also made progress with its second candidate PTX-100, a GGT1 inhibitor for rare lymphomas that according to Edison could be taken by the biotech through a pivotal trial before outlicensing.

It is currently planning a clinical trial of the drug in RhoA-mutant lymphomas in mid-2018, and Edison says Prescient "could potentially commercialize PTX-100 in the U.S. with a small sales force."