Ticagrelor is an approved blood thinner, or compound that prevents blood platelet clumping. Its maker, AstraZeneca, is also looking at it as a potential treatment for sickle cell disease.

AstraZeneca markets ticagrelor in the United States under the brand name Brilinta and Brilique in the rest of the world. People who have had a heart attack use it to reduce their risk of developing blood clots and having a stroke or another heart attack.

AstraZeneca is investigating whether ticagrelor could be an effective way to reduce blood vessel blockages in sickle cell disease patients. Blood vessel blockades, or vaso-occlusive crises (VOCs), are a common cause of pain in these patients.

How ticagrelor works

Platelets are a type of blood cell. Their role is to form clumps, or clots, to stop bleeding when a blood vessel is damaged. Platelets do not form clots until they are activated, typically by contact with a damaged blood vessel wall.

Sickle cell disease patients have more activated platelets than normal. This makes it more likely that sickle cells will stick to blood vessel walls or that other clumps of blood cells will form, increasing the frequency of blood vessel blockages.

It interacts with a protein receptor called P2Y12 that is found on the surface of platelets and plays an important role in regulating clotting. Ticagrelor is an antagonist to the receptor, which means that it blocks it. Blocking P2Y12 reduces clotting or platelet clumping. The hope is that it will reduce the frequency of blood vessel blockages in sickle cell disease patients.

Ticagrelor in clinical trials

A Phase 1 trial (NCT03126695) in 44 healthy volunteers examined how well the body absorbed ticagrelor from different types of oral tablets. The study completed in 2017 and results were published in August 2019. The results showed that all formulations were well-tolerated with similar bioavailability of the drug.

The first clinical trial in sickle cell disease patients was the Phase 2 study (NCT02214121), called HESTIA1. In the study, pediatric patients ages 3 to 17 years were given one of two dosing schedules for part A of the study and then given one of 2 doses or placebo for an optional part B of the study. The study investigated the pharmacokinetics, or how the drug moves through the body, and pharmacodynamics, or how the drug affects the body, of the drug. Results of the study were published in the American Journal of Hematology in December 2018. The study found dose-dependent increases in blood levels of ticagrelor and decreases in platelet activity. No differences were found between pain ratings or numbers of adverse events between the treatment groups or placebo.

The objective of another Phase 2 trial (NCT02482298), called the HESTIA2 study, was to see if ticagrelor could reduce the frequency and intensity of adult patients’ pain events. Raw results from the study have been posted on the clinical trial’s website and were published in the British Journal of Haematology in January of 2019. The study was done in 87 adult patients, ages 18-30, with sickle cell disease. Patients were randomized between two dosages of ticagrelor or placebo. All patients went through a 4 week blinded placebo phase to establish baseline pain levels and then the groups were randomized into their treatment groups for 12 weeks followed by a 2-week follow-up period. The study found no difference in pain levels between the three groups, however.

The Phase 3 HESTIA3 study (NCT03615924) is investigating if ticagrelor can reduce VOCs in pediatric patients. 193 patients ages 2 to 17 have been recruited for the trial. The trial design was published in Contemporary Clinical Trials in August 2019. Participants will receive either a weight-adjusted dose of ticagrelor or a placebo for 1 to 2 years. The number of VOCs over this time period will be monitored along with related secondary outcomes including number of painful crises, intensity of pain, fatigue score, and type of analgesic used. The study has finished recruitment and is expected to conclude in October of 2020.

AstraZeneca studied the effects of ticagrelor in patients younger than 24 months in the Phase 1 HESTIA4 trial (NCT03492931). Twenty-one children between 3 and 21 months of age with sickle cell disease were given a single age-dependent oral dose of ticagrelor. Blood samples were taken at 1, 2, 4, and 6 hours after dosing in order to monitor the pharmacokinetics of the drug. Results of the study were published in November of 2019 in the journal Blood. The results showed that ticagrelor was well-tolerated and followed expected exposures in this young patient population.


Last updated: Jan. 2, 2020


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