These red blood cells (RBCs) are often quickly destroyed and cause anemia, where the blood cannot deliver sufficient amounts of oxygen to tissues and organs. Sickle cells also tend to stick together and block blood flow in small blood vessels, leading to painful episodes known as vaso-occlusive crises.
The U.S. Food and Drug Administration (FDA) granted olinciguat orphan drug status in 2018 as a potential treatment of sickle cell disease.
How does olinciguat work?
Studies suggest that many symptoms of sickle cell disease are due 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.
In sickle cell disease, the sickle-shaped blood cells rupture and release hemoglobin and an enzyme called arginase into the bloodstream. Hemoglobin and arginase reduce the overall availability of nitric oxide in the blood, leading to lower soluble guanylate cyclase (sGC) production. sGC is a key enzyme of the nitric oxide signaling pathway.
Olinciguat is a compound that aims to stimulate sGC production, leading to the production of a signaling molecule called cyclic guanosine monophosphate (cGMP). High levels of cGMP help reduce inflammation in blood vessels, decrease adhesion between RBCs, and allow for improved blood flow by increasing the availability of nitric oxide. Doing so should ease disease symptoms of the disease and prolong patients’ lives.
Olinciguat in clinical trials
The safety and tolerability of olinciguat were investigated in various studies.
A Phase 1 randomized, double-blind clinical trial (NCT02572349) evaluated the safety, tolerability, pharmacokinetics (movement in the body), and pharmacodynamics (effects on the body) of olinciguat when administered orally as a single dose to healthy volunteers. A similar Phase 1 clinical trial (NCT02792998) with multiple ascending doses of olinciguat was also conducted.
Results of both studies showed that 1 to 6 mg of olinciguat was well-tolerated with no serious adverse events. Those treated showed a consistent increase in cGMP levels, and a decrease in blood pressure indicating sGC stimulation. Olinciguat was also seen to have low clearance from the kidneys, meaning it could be used by patients with troubled kidney function.
A Phase 2 clinical trial (NCT03285178), called STRONG SCD, is underway to evaluate the safety and tolerability of four, low-to-high doses of once-daily olinciguat tablets, against placebo, in patients with stable sickle cell disease. The 12-week trial, now recruiting up to 88 people, ages 16 to 70, is taking place at sites across the U.S. and in Lebanon. It is expected to finish in July 2020.
Last updated: Dec. 6, 2019
Sickle Cell Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.