IW-1701 is an investigational medicine being developed by Ironwood Pharmaceuticals for the treatment of sickle cell anemia, a disease in which the body produces sickle, or crescent-shaped, red blood cells. These blood cells are quickly destroyed, which leads to the development of anemia, a condition in which the blood cannot deliver enough oxygen throughout the body.

How IW-1701 works

Studies suggest that many symptoms of sickle cell anemia may be linked to nitric oxide deficiency in the blood. Nitric oxide is a free radical produced by various cells and used as a signaling molecule. It induces a coordinated program of cellular events that promote blood flow. Patients with sickle cell anemia have a reduced bioavailability of nitric oxide.

IW-1701 is an investigational compound that stimulates an enzyme called soluble guanylate cyclase (sGC), which plays a key role in the production of nitric oxide. The stimulation of sGC leads to certain intracellular activities that restore the reduced bioavailability of nitric oxide in blood and increase blood flow. This increase in the levels of nitric oxide and blood flow is believed to stop the destruction of blood cells and ultimately help address the symptoms of sickle cell anemia.

IW-1701 in clinical trials

The safety and tolerability of IW-1701 have been investigated in various studies. A randomized, double-blind, placebo-controlled Phase 1 study (NCT02572349) evaluated the safety, tolerability, pharmacokinetics (movement in the body), and pharmacodynamics (effect and mechanism of action) of IW-1701 when administered orally as single doses to healthy volunteers. The study’s main objective was to assess the safety and tolerability of single ascending dose levels of IW-1701 versus placebo. The results of this study have not been published yet.

A randomized, placebo-controlled Phase 1b multiple ascending dose study (NCT02792998) of IW-1701 tablets also evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of the treatment in healthy volunteers. Ironwood Pharmaceuticals presented data from this study at the 2017 American Society of Hematology Annual Meeting. The data indicated that IW-1701 has the potential to improve nitric oxide signaling and address the symptoms of both acute and chronic sickle cell anemia.

Based on these promising results, the company initiated a multicenter, randomized, double-blind placebo-controlled Phase 2 trial (NCT03285178) called STRONG-SCD to evaluate the safety and tolerability of oral, once-daily IW-1701 in patients with sickle cell anemia. Among the study’s objectives is the evaluation of the pharmacokinetic profile of IW-1701 and its effects on symptoms of sickle cell anemia, health-related quality of life, and biomarkers of pharmacodynamic activity. The study is not yet open for participant recruitment.

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