Prothena gets a positive snapshot of efficacy for rare disease drug, preps for PhIII

A small Phase I/II study of Prothena's lead drug produced an encouraging round of initial responses among patients with AL amyloidosis, a rare threat to organs. And now company execs say they're going straight into a Phase III study of NEOD001 so they can build a case for regulators.

Among 14 cardiac patients who were evaluable at this stage, the biotech says that half demonstrated a significant reduction in levels of NT-proBNP, a biomarker they used which can indicate their risk of dying. And 6 of 14 evaluable renal patients--42.9%--had a significant drop in proteinuria in the absence of estimated glomerular filtration rate (eGFR) worsening.

Historical rates of response "would have predicted 26.5% cardiac and approximately 24% renal response rates in patients treated solely with off-label standard of care," said Chief Scientific Officer Gene Kinney.

Shortly after the company released the early data and plans for late-stage work on Tuesday evening, the news from the company took a sudden and unexpected twist. Prothena CEO Dale Schenk, the former CSO at Elan, posted a letter alerting investors to his recent diagnosis of pancreatic cancer. "I am pleased to report that the cancer was caught early and I am doing well," he wrote, adding that he expected to stay active with the company as he underwent treatment. Being a scientist, he added, was a great benefit at a time like this.

Overall, the news on Prothena's lead program had little impact on its stock price, which edged up about 2% in after-hours trading.

Prothena CSO Gene Kinney

Prothena ($PRTA) was spun out of Elan (which was later acquired for its royalty stream) back in 2012, giving the biotech a chance to sort through its R&D assets to come up with an optimal portfolio of experimental therapies. Longtime observers of the biotech scene will recall that Elan was an early pioneer in Alzheimer's, advancing one of the first amyloid beta drugs (bapineuzumab) under J&J's guidance through a high-profile Phase III flop. And Kinney is the former head of research at J&J's Janssen Alzheimer Immunotherapy R&D group.

But there was still a decade's worth of work on amyloid and amyloid diseases to back up their efforts on AL amyloidosis, says Kinney. The disease is caused by the misfolding of a protein, with amyloid deposits building up in organs like the heart and kidneys and causing them to fail.

Prothena is an unusual transatlantic hybrid, with the company based in the low-tax environs of Dublin and a lab in the South San Francisco biotech hub. Neil Woodford, who's been getting more deeply involved in biotech investing, recently gambled $50 million on Prothena's pipeline.

The study now being discussed is being done in two parts. The first was an open-label study doing dose-escalation work on 7 cohorts of patients with any systemic organ involvement where investigators were looking at biomarkers of the disease. The second, upcoming segment will run parallel with the Phase III with a closer focus on cardiac and renal involvement.

"We'll be initiating Phase III when we make this announcement," Kinney told FierceBiotech. The Phase III will be run as a multinational study with 50 to 60 sites in the U.S. and Europe. Investigators will have 18 to 30 months for recruitment and then expect to follow patients for 12 to 18 months of therapy.

Kinney says there are about 15,000 cases of AL amyloidosis  in the U.S. and Europe, though he suspects that the disease is underdiagnosed right now. And the biotech isn't alone in the field. Takeda has the most advanced program in the clinic for amyloidosis with ixazomib, and is also jumping from Phase I straight into Phase III after getting a "breakthrough" drug designation from the FDA.

"NEOD001 potentially holds significant promise for patients with AL amyloidosis as we now see clinically meaningful decreases in both cardiac and renal biomarkers with monthly NEOD001 infusions," said Tufts Professor Raymond L. Comenzo. "NEOD001 appears to be the first agent that works directly to address the buildup of light-chain (AL) amyloid in organs. The results presented today strongly support moving into a Phase III trial, which I believe is designed to test whether or not NEOD001 provides meaningful clinical benefit for patients with AL amyloidosis."

- here's the press release