An upcoming analysis by the Institute for Clinical and Economic Review (ICER) will compare the clinical efficacy and economic value of Novartis’ crizanlizumab and Global Blood Therapeutics‘ voxelotor, lead candidate therapies for sickle cell disease (SCD).
ICER’s report will be discussed during its New England Comparative Effectiveness Public Advisory Council meeting, scheduled for March 2020.
During the Open Input Period, which runs through Aug. 27, ICER will accept comments from patients and other stakeholders on the therapies included in the report. Stakeholders are encouraged to submit commentary, specifically on “important patient-relevant and patient-centered outcomes, especially those not adequately captured in the clinical trial data,” and “other benefits and disadvantages.”
“It’s important to us that we know what matters to you — the patient — to make sure our reports can support policies and guidelines that help make sure patients can access, and afford, the most effective treatments,” ICER says at the start of its questionnaire. “We want to hear from you.”
The council meeting is currently scheduled for March 26, but the venue has not been announced.
Crizanlizumab (SEG101) is a lab-made monoclonal antibody that binds to the protein P-selectin, which is found on surface platelets and endothelial cells, which are the cells lining the inner walls of blood vessels. P-selectin usually acts to regulate the movement of white blood cells — a type of immune cell — through blood vessels. It normally regulates how the white blood cells stick to the vessel walls during inflammation and tissue repair. However, in people with SCD, P-selectin is involved in the adhesion of sickle red blood cells to blood vessels. This prevents the normal blood flow, causing inflammation and pain crises.
By blocking P-selectin, crizanlizumab may prevent these processes from occurring and help maintain normal blood flow. Crizanlizumab is currently under FDA priority review as a potential treatment for vaso-occlusive crises (VOCs), also called pain crises, in people with SCD. The FDA’s decision is expected in early 2020.
VOCs are unpredictable, acute episodes of severe pain, and are linked with serious, life-threatening complications. They are the primary reason why people with sickle cell disease seek medical care at emergency departments, and require hospital admissions.
The study enrolled 198 people with SCD and a history of two to 10 pain crises in the previous year. Participants received either a low dose (2.5 mg/kg), a high dose of crizanlizumab (5 mg/kg), or a placebo delivered into the blood 14 times over a period of 52 weeks (every four weeks).
Those treated with the highest dose tested (5 mg/kg) showed a decrease of 45.3% in the median annual rate of VOCs compared with those receiving placebo. That percentage held whether or not the patients were treated with hydroxyurea.
Crizanlizumab also increased the numbers of patients who never experienced VOCs over the course of the study (36%) relative to placebo (17%). In the high-dose group, time until the first crisis was 2.9 times longer (4.07 vs 1.38 months). In addition, those given crizanlizumab had lower annual rates of days hospitalized compared with patients on placebo (4.00 vs 6.87).
Voxelotor, formerly known as GBT440, is an oral, once-daily therapy for SCD. It was designed to increase hemoglobins’ affinity for oxygen. That prevents hemoglobins from sticking together, and the resulting sickling of red blood cells.
The trial randomly selected 274 SCD patients to receive 1,500 mg or 900 mg per day of voxelotor or a non-active placebo, for at least 24 weeks.
The results showed that treatment with a high dose of voxelotor significantly reduced, in comparison to before therapy, the mean levels of reticulocytes (immature red blood cells, a reduction by 19.9%) and bilirubin (by 29.1%) — two biomarkers of blood cells damage.The treatment also increased the amount of hemoglobin in a total of 74 (48.4%) patients compared with seven (9%) in the placebo-treated group.
The results showed that treatment with a high dose of voxelotor significantly reduced the mean levels of two biomarkers of blood cells damage, in comparison with their levels before therapy. The levels of reticulocytes, or immature red blood cells, decreased by 19.9%, while the levels of bilirubin were reduced by 29.1%. The treatment also increased the amount of hemoglobin in 74 (48.4%) patients compared with seven (9%) in the placebo-treated group.
The U.S. Food and Drug Administration granted voxelotor a breakthrough therapy designation in January 2018. The European Medicines Agency also has included volexotor in its Priority Medicines (PRIME) program.
Voxelotor is undergoing clinical investigation in two trials as part of the GBT HOPE program, designed to further demonstrate the therapy’s safety and capacity to modify the course of the disease. The trials are the Phase 2 study, HOPE-KIDS 1 (NCT02850406), still recruiting participants, and the pivotal Phase 3 study, GBT_HOPE (NCT03036813).
Global Blood Therapeutics is planning to file a new drug application for voxelotor by the end of 2019.