Potential PAH Treatment, a Soluble Guanylate Cyclase Stimulator, Will Advance in Testing Based on Phase 1a Trial Results

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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PAH clinical trial

Ironwood Pharmaceuticals, Inc. recently announced positive top-line results from a Phase 1a clinical trial of IW-1701, an investigational soluble guanylate cyclase (sGC) stimulator that is part of the pharmacologically distinct library of sGC compounds discovered by Ironwood.

An enzyme, sGC is crucial to the physiological control of blood flow, inflammation, and fibrosis. For this reason, modulating the sGC signaling pathway might be beneficial for people with vascular and fibrotic diseases like pulmonary arterial hypertension (PAH).

The clinical trial was a single ascending dose, double-blind, placebo-controlled study in which 24 healthy volunteers were randomly assigned to receive a single dose of IW-1701 or placebo as an oral capsule.

Results showed that IW-1701 was well-tolerated, and met the anticipated cardiovascular pharmacodynamic effects, biomarker-based confirmation of target engagement, and a dose-proportional pharmacokinetic profile appropriate for once-a-day dosing and consistent with distribution into tissues. These results will be presented at a future medical congress.

Preclinical and clinical data reported to date supports the continued development of IW-1701, the company said in a  press release. Ironwood is planning to begin a Phase Ib multiple ascending dose trial by June 2016, with top-line results anticipated by the year’s end.

“Soluble guanylate cyclase is part of a signaling pathway that regulates blood flow, inflammation and fibrosis, which is why sGC stimulators offer such a breadth of therapeutic potential in vascular and fibrotic diseases such as congestive heart failure and diabetic nephropathy, as well as certain orphan diseases such as pulmonary arterial hypertension, Duchenne muscular dystrophy and achalasia, among others,” said Mark Currie, PhD, chief scientific officer and president of research and development at Ironwood. “Today’s positive Phase Ia results with IW-1701 — along with our recent positive Phase Ia data with our other clinical sGC stimulator IW-1973 — demonstrate that Ironwood’s sGC stimulators have attractive pharmacologic and pharmacokinetic profiles, providing multiple opportunities to develop therapies that, if approved, can address important unmet needs.”

Phase 2 studies are also being planned for both IW-1701 and IW-1973, which have different pharmacological profiles. The company expects to start these clinical trials later in 2016.


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