What Is Etavopivat?
Etavopivat is an investigational medication that is administered orally. It is currently being developed by Novo Nordisk A/S to treat individuals with sickle cell disease (SCD). Etavopivat is also under investigation for thalassemia, liver diseases, and myelodysplastic syndromes (MDS). Clinical trials are exploring etavopivat's potential effects on the body, its safety profile, and its effectiveness in managing these conditions. Researchers are also investigating how etavopivat interacts with other medicines in healthy participants. For example, one study aims to determine the effect of etavopivat on the electrical activity of the heart in healthy participants. Another study investigates whether the use of etavopivat affects the breakdown and metabolism of commonly used medicines in the body. The medication is typically taken as a daily oral dose, sometimes as 2 tablets administered in a fasted state.
Uses and Conditions Under Study
Etavopivat is primarily being studied for its potential to treat certain blood disorders and other conditions:
- Sickle Cell Disease (SCD): This is a genetic blood disorder where red blood cells become rigid and C-shaped, leading to anemia, pain, and organ damage. Etavopivat is being developed to treat individuals with SCD, with 9 trials currently investigating its effects.
- Thalassemia: Another genetic blood disorder, thalassemia causes the body to produce less hemoglobin, resulting in anemia. Etavopivat is under investigation for its potential role in treating thalassemia, with 4 trials exploring this use.
- Liver Diseases: One trial is studying etavopivat in individuals with liver diseases. This research likely aims to understand how liver function affects the body's processing of the drug and its safety in this population.
- Myelodysplastic Syndromes (MDS): One trial is also exploring etavopivat for very low risk, low risk, or intermediate risk MDS. MDS are a group of blood cancers where the bone marrow produces abnormal blood cells.
Additionally, several studies involve healthy volunteers. These trials, including 2 dedicated trials for healthy participants and others involving both healthy volunteers and patients, are crucial for understanding etavopivat's safety, how it is processed by the body (pharmacokinetics), and its potential interactions with other medications.
Dosing
Etavopivat is administered orally, primarily as tablets. The medication is typically taken as a daily dose. Studies have investigated various dosing regimens, including single doses and daily administration.
A common strength being studied is 400 mg, taken once daily (QD). This 400 mg daily dose has been investigated for sickle cell disease, including in patients requiring transfusions, and for thalassemia, both transfusion-dependent and non-transfusion-dependent forms.
Some trials have also explored "Low Dose" and "High Dose" etavopivat, as well as different administration conditions such as taking the medication in a fasted state. Studies have also looked at how liver function might affect dosing, with different doses (referred to as Dose 1 and Dose 2) being investigated for mild, moderate, and severe hepatic impairment compared to healthy matched controls.
Etavopivat has been studied in a broad age range. This includes participants 12 years and older with sickle cell disease or thalassemia. Pediatric studies have also included participants 2 years to less than 12 years old with sickle cell disease.
Side Effects
In an open-label study (NCT05568225) of Etavopivat for anemia in patients with Myelodysplastic Syndromes (MDS), specific side effect frequencies were not reported with placebo comparisons. Instead, the study documented the number of adverse events (AEs), serious adverse events (SAEs), and events considered related to Etavopivat treatment across different patient groups.
- For patients with a High Transfusion Burden:
- There were 54 serious adverse events reported.
- 6 adverse events were considered related to Etavopivat.
- Two dose reductions were reported.
- For patients with a Low Transfusion Burden:
- There were 33 serious adverse events reported.
- No adverse events were considered related to Etavopivat.
- No premature discontinuations, dose interruptions, or dose reductions were reported.
- For patients who were Non-transfusion Dependent:
- There were 33 serious adverse events reported.
- No adverse events were considered related to Etavopivat.
- One dose reduction was reported.
The total number of all adverse events reported across the groups were 6 for high transfusion burden, 3 for low transfusion burden, and 8 for non-transfusion dependent patients. No premature discontinuations or dose interruptions were reported in any group.
Clinical Trial Results
Results from an open-label study (NCT05568225) investigated the effects of Etavopivat in patients with Myelodysplastic Syndromes (MDS) across different transfusion needs.
Hematologic Improvement-Erythroid (HI-E) Response
Within 24 weeks of Etavopivat treatment, participants showed varying rates of Hematologic Improvement-Erythroid (HI-E) response, defined as an improvement lasting at least 8 weeks:
- 50% of participants with a Low Transfusion Burden achieved an HI-E response.
- 25% of participants with a High Transfusion Burden achieved an HI-E response.
- No HI-E response was observed in non-transfusion dependent participants.
Reduction in Red Blood Cell (RBC) Transfusions
For patients who were transfusion-dependent at the start of the study, Etavopivat treatment led to reductions in RBC transfusions over 8 weeks:
- Participants with a High Transfusion Burden experienced a mean reduction in total RBC units ranging from 5.8 to 7.5 units. The percent change from baseline in transfusion independence for these patients showed reductions ranging from 50.00% to 127.78%.
- Participants with a Low Transfusion Burden experienced a mean reduction in total RBC units ranging from 2.5 to 5.5 units. The percent change from baseline in transfusion independence for these patients showed varied results, including reductions up to 58.33%, but also some increases in transfusion units (up to 33.33% and 20.83%).
Changes in Neutrophil and Platelet Counts
The study also assessed changes from baseline in neutrophil and/or platelet counts:
- Non-transfusion dependent participants showed a mean increase of 43.0 x 10^9 cells per liter in one measure of neutrophil and/or platelet counts. Another measure showed a mean decrease of 3.2 x 10^9 cells per liter.
- Participants with a High Transfusion Burden experienced mean decreases in neutrophil and/or platelet counts, specifically 8.0 x 10^9 cells per liter and 0.100 x 10^9 cells per liter.
- Participants with a Low Transfusion Burden also experienced mean decreases, specifically 0.950 x 10^9 cells per liter and 51.0 x 10^9 cells per liter.
Currently Recruiting Trials
Etavopivat is an investigational medicine being studied for its potential to treat blood disorders like sickle cell disease and thalassemia. Several clinical trials are currently enrolling participants to further evaluate its safety and effectiveness.
One ongoing Phase 3 study, NCT06612268, sponsored by Novo Nordisk A/S, is evaluating how well etavopivat works to reduce the number of vaso-occlusive crises (VOCs), which are painful sickle cell crises caused by blood vessel obstructions. This study aims to enroll 408 adults and adolescents living with sickle cell disease.
Another Phase 3 research study, NCT06609226, also sponsored by Novo Nordisk A/S, is investigating the long-term treatment with etavopivat in people with sickle cell disease or thalassemia. These are inherited blood disorders that affect hemoglobin, the protein responsible for carrying oxygen throughout the body. This study is seeking to enroll 480 participants aged 12 years and older with either sickle cell disease (transfusion-dependent or not) or thalassemia (transfusion-dependent or not), as well as children aged 2 to less than 12 years old with sickle cell disease.
For pediatric patients, Forma Therapeutics, Inc. is sponsoring a Phase 2 open-label study, NCT05953584. This trial is evaluating etavopivat's activity on transcranial Doppler velocities in children with sickle cell disease who are at an increased risk for primary stroke. It will also assess the medicine's safety and helpfulness, with an enrollment target of 27 participants.
Additionally, a Phase 2 study, NCT06198712, sponsored by Forma Therapeutics, Inc., is learning about the pharmacokinetics and safety of etavopivat, a once-daily oral medicine, in adolescents with sickle cell disease. This study aims to understand how long etavopivat stays in the bloodstream and if it offers benefits, with an enrollment target of 50 participants.
Where to Participate
Clinical trials for etavopivat are being conducted across a broad geographic area to ensure diverse participation. Studies are active at 69 sites located in 50 cities across 30 states.
Top participating locations include:
- The Bronx, New York (4 sites)
- Los Angeles, California (4 sites)
- Atlanta, Georgia (3 sites)
- Chicago, Illinois (3 sites)
- Memphis, Tennessee (3 sites)
- Tacoma, Washington (3 sites)
- Orange, California (3 sites)
- Greenville, North Carolina (3 sites)
- Durham, North Carolina (3 sites)
- New York, New York (3 sites)
Eligibility for these trials generally includes participants between 2 and 18 years of age, of all genders. Healthy volunteers are not being recruited for these specific studies, as the focus is on patients with sickle cell disease or thalassemia.
Development Timeline
The development journey for etavopivat began on November 12, 2020, with its first clinical trial. Initially, Forma Therapeutics, Inc. led the early research, sponsoring five trials, before Novo Nordisk A/S took over as the primary sponsor for eight subsequent studies, including the current Phase 3 trials.
Etavopivat's pipeline has steadily expanded since its inception. Early investigations explored conditions such as IBS-C and hyperphosphatemia, and also included studies in healthy volunteers. The focus then broadened to specifically address blood disorders, with trials for healthy volunteers with sickle cell disease, thalassemia, and liver diseases. The drug's development also included studies for very low risk, low risk, or intermediate risk MDS per IPSS-R, demonstrating a diverse exploration of its potential applications.
To date, a total of 13 clinical trials have been conducted or are ongoing for etavopivat, involving an estimated 1,655 participants. The development has progressed through all phases, with 5 trials in Phase 1, 5 in Phase 2, and 3 currently in Phase 3. The latest trial is projected to conclude by June 15, 2025, marking continued progress in bringing this potential treatment to patients.