GBT Presents Data on New Sickle Cell Disease Pipeline Therapies with Best-in-Class Potential – Inclacumab and GBT021601

IndustryPRwire -- Global Blood Therapeutics announced new preclinical data on its sickle cell disease (SCD) pipeline therapies – inclacumab, a novel P-selectin inhibitor in development to reduce the frequency of vaso-occlusive crises (VOCs) in patients with SCD, and GBT021601, a next-generation hemoglobin S (HbS) polymerization inhibitor. These data are being presented at the all-virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

Ted W. Love, M.D., president and chief executive officer of GBT. Commented “In pursuit of our mission to transform the treatment of and care for people living with sickle cell disease, our research and development pipeline is targeting multiple pathologies, including vascular occlusion and hemoglobin polymerization, We’re very excited about the best-in-class potential of both inclacumab and GBT021601. In 2021, we plan to initiate two pivotal Phase 3 clinical trials evaluating inclacumab for its ability to reduce the frequency of VOCs and hospital readmissions caused by VOCs. In addition, this is the first time we are presenting data on GBT021601. These preclinical data are very promising, and we look forward to studying the safety and efficacy of this potentially innovative therapy in SCD patients once we enter the clinic as planned in the near future.”

Inclacumab: In Vitro Analysis and Phase 3 Clinical Study Program

In vitro study results (Abstract #1707) demonstrated that inclacumab has the potential to be a best-in-class P-selectin inhibitor for reducing the frequency of VOCs in patients with SCD. When characterized alongside crizanlizumab, an FDA-approved P-selectin inhibitor for treatment of VOCs, inclacumab:

  • Binds P-selectin at the natural ligand binding site and has an affinity similar to crizanlizumab,
  • Demonstrated rapid binding kinetics to P-selectin and remained bound for longer, and
  • Inhibited platelet-leukocyte aggregation to a greater extent than crizanlizumab.

Additionally, prior clinical experience with inclacumab in more than 700 non-SCD participants demonstrated the potential for a substantially longer duration of exposure and near complete inhibition of platelet-leukocyte aggregation over a 12-week period. Taken together, we believe these characteristics will translate into quarterly dosing, improved patient adherence, and the potential to expand use to a broader patient population.

In 2021, GBT plans to initiate two global, randomized, placebo-controlled pivotal Phase 3 trials evaluating safety and efficacy of inclacumab. These trials are designed to enhance understanding of how P-selectin inhibitors could provide clinical benefit for patients with SCD and reduce overall healthcare utilization. One study is designed to reduce the frequency of VOCs over one year in patients with SCD when treated with inclacumab (30 mg/kg) or placebo every 12 weeks. The second study will evaluate inclacumab based on a primary endpoint of 90-day hospital readmission rates following a VOC hospitalization. Participants in that trial will receive either a single dose of inclacumab (30 mg/kg) or placebo, peri-discharge following a VOC hospitalization. Approximately 50 percent of U.S. SCD patients with least two annual VOC events are re-admitted within 90 days following a VOC hospitalization. Initiation of both trials is expected in the first half of 2021.

GBT021601: Preclinical Analysis of Next Generation HbS Polymerization Inhibitor

Preclinical data (Abstract #1704) on GBT021601, a molecule discovered and designed by scientists at GBT, demonstrated its potential as a potent next-generation HbS polymerization inhibitor. GBT021601 has the same mechanism of action as Oxbryta® (voxelotor) tablets, but with the potential for greater efficacy by achieving higher hemoglobin (Hb) occupancy at significantly lower doses. The study showed that GBT021601 normalized Hb levels in Townes sickle cell mice. In addition, in this study GBT021601 was highly effective in:

  • Reducing hemolysis,
  • Prolonging red blood cell (RBC) lifespan,
  • Improving RBC health, and
  • Potentially improving organ function.

Following treatment with GBT021601, levels of erythropoietin (EPO), a hormone that plays a key role in the production of RBCs, did not change – indicating that the observed increase in Hb levels was safe and was not due to hypoxic response.

A Phase 1 clinical study on the safety and tolerability of GBT021601 in SCD patients is expected to begin by mid-2021.

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