Potential Treatment Targeting Nitric Oxide Levels, Olinciguat, Named Orphan Drug by FDA

The U.S. Food and Drug Administration (FDA) recently granted orphan drug status to olinciguat (IW-1701) as a potential treatment of sickle cell disease (SCD), Ironwood Pharmaceuticals announced.

Evidence suggests that the symptoms of sickle cell disease may be associated with nitric oxide deficiency in the blood. Nitric oxide is a free radical produced by several cells and used as a signaling molecule that works to induce cellular events that promote blood flow. Patients with sickle cell anemia have a reduced bioavailability of nitric oxide.

Olinciguat is an oral investigational therapy that stimulates an enzyme called soluble guanylate cyclase (sGC), known to play a key role in the production of nitric oxide.

The stimulation of sGC can restore the bioavailability of nitric oxide in the blood to increase blood flow, which may stop the destruction of blood cells and help address disease symptoms.

“There is an urgent need for new, innovative treatments for patients with sickle cell disease, a debilitating and potentially fatal inherited blood disorder that causes painful crises, organ damage and other serious complications,” Christopher Wright, MD, PhD, senior vice president of global development and chief development officer at Ironwood Pharmaceuticals, said in a press release.

“The orphan drug designation adds momentum to our clinical program investigating olinciguat, which has the potential to improve multiple aspects of sickle cell disease pathophysiology. The designation is also an important milestone in Ironwood’s evolution as we advance our pipeline of sGC stimulators focused on the treatment of serious and orphan diseases.”

Olinciguat is currently being evaluated in the Phase 2 STRONG-SCD clinical trial (NCT03285178), currently enrolling a planned 88 patients, ages 16 to 70, at five U.S. sites.

The double-blind, placebo-controlled, and dose-ranging study is evaluating the safety, tolerability, pharmacokinetics (how an organism affect a drug) and pharmacodynamics (how a drug affects an organism) of olinciguat tablets in patients with stable sickle cell disease. They will be randomized to a low, medium, or high dose, or to placebo, for 12 weeks. The study is expected to finish in July 2019.

Olinciguat’s safety and tolerability were studied in a Phase 1 (NCT02572349) and Phase 1b trial (NCT02792998) in healthy volunteers. In the Phase 1b trial which evaluated a range of doses, olinciguat showed a potential to improve nitric oxide signaling, which may address the symptoms of both acute and chronic sickle cell disease, according to data presented at a 2017 scientific conference.

Orphan drug status is granted to products intended to treat, prevent or diagnose rare diseases or diseases that affect fewer than 200,000 people in the United States. The regulatory designation provides certain benefits, such as a period of market exclusivity, and fee waivers and tax credits.