Experimental treatment NM3086 seems to work as designed: Study

Phase 1 study was a first in-human clinical trial of therapy

Marisa Wexler MS avatar

by Marisa Wexler MS |

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NM3086, an experimental therapy for paroxysmal nocturnal hemoglobinuria (PNH) that’s designed to block the alternative complement pathway’s activation, was generally well tolerated in a first in-human clinical trial.

Findings from the Phase 1 study with healthy volunteers suggest NM3086 is working as intended, according to its developer, NovelMed.

“Early success in Phase I studies marks the first clinical milestone towards the development of NM3086 as a safe [alternative complement pathway] blocker for anemia in PNH and other complement-mediated disorders,” the company explained in a press release.

“We continue to be impressed by the data from in vitro and clinical trial studies, which confirm the potential of NM3086 to outperform other drug candidates in the complement space,” said Robert Bard, the company’s vice president of regulatory affairs.

The complement system, also known as the complement cascade, comprises a group of immune proteins in blood and other bodily fluids. These proteins are normally in an inactive state, but they can become activated to drive a powerful inflammatory response under certain conditions.

While the complement cascade is important for defending against threats, its abnormal activation is known to drive the destruction of blood cells in PNH.

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NM3086’s effect on complement system

All the approved treatments for PNH work by blocking complement activation. While they can effectively ease disease symptoms, blocking this important part of the immune system raises the risk of infections.

There are two general molecular pathways that can trigger the complement system — the classic pathway and the alternative pathway.

NM3086 is designed to block the alternative pathway, the main driver of blood cell destruction in PNH. It works by targeting properdin, an alternative complement protein.

By leaving the classical pathway untouched, NM3086 would reduce blood cell destruction but allow the complement system to activate in response to infectious threats. This may help lower the risk of infections associated with therapies that inhibit both pathways.

In the Phase 1 trial, healthy volunteers were given a single dose of NM3086 (0.1-20 mg/kg), or a placebo. They were followed for up to 90 days, or about three months.

Data showed NM3086 was safe and well tolerated at all tested doses, according to NovelMed.

Biomarker data also indicated NM3086 blocked the alternative complement pathway in a dose-dependent manner with the maximum 20 mg/kg dose blocking alternative complement activation for more than six weeks, but the classical pathway wasn’t affected.

“This is the first clinical study to demonstrate that selective blockade of the [alternative pathway] can be safely achieved by neutralizing properdin, a critical protein in the [alternative pathway] cascade,” said Rekha Bansal, PhD, NovelMed’s CEO.