FDA Grants Orphan Drug and Rare Pediatric Disease Designations to GBT’s Treatments for Sickle Cell Disease

The U.S. Food and Drug Administration has granted both Orphan Drug and Rare Pediatric Disease designations to Global Blood Therapeutics’ inclacumab and GBT601 for the treatment of sickle cell disease.

Photo: Kim Smith-Whitley, executive vice president and head of research and development at GBT

Sickle cell disease (SCD) is a lifelong inherited rare blood disorder that impacts hemoglobin, a protein carried by red blood cells that delivers oxygen to tissues and organs throughout the body. Due to a genetic mutation, individuals with SCD form abnormal hemoglobin. Through a process called hemoglobin polymerization, red blood cells become sickled, crescent-shaped and rigid. The recurrent sickling process causes destruction of the red blood cells and hemolytic anemia (low hemoglobin due to red blood cell destruction) and blockages in capillaries and small blood vessels (vaso-occlusion), which impede the flow of blood and oxygen delivery throughout the body, commonly referred to as vaso-occlusive crises (VOCs). The diminished oxygen delivery to tissues and organs can lead to life-threatening complications, including stroke and irreversible organ damage. Complications of SCD begin in early childhood and can include neurocognitive impairment, acute chest syndrome, and overt stroke, among other serious issues.

GBT’s inclacumab, exclusively licensed under an agreement with Roche, is a novel P-selectin inhibitor currently in phase 3 clinical trials to evaluate its potential to reduce the occurrence of vaso-occlusive crises (VOCs) and readmissions due to VOCs in patients with SCD. GBT601, a next-generation sickle hemoglobin (HbS) polymerization inhibitor, is being studied in a restarted phase 1 clinical trial and is expected to advance into the phase 2 portion of a phase 2/3 trial by mid-year.

“The FDA’s orphan drug and rare pediatric disease designations for both inclacumab and GBT601 are an acknowledgment of the critical and ongoing unmet need in sickle cell disease and the potential of GBT’s innovative pipeline of investigational medicines,” said Kim Smith-Whitley, executive vice president and head of research and development at GBT. “We believe that both inclacumab and GBT601 have the potential to be best-in-class therapeutic options for the treatment of this devasting disease.”

VOCs take a significant toll on patients and are a leading cause of hospital readmissions in SCD. Patient enrollment is currently ongoing in two randomized, double-blind, placebo-controlled phase 3 clinical trials evaluating the safety and efficacy of inclacumab, dosed quarterly, for the potential treatment of VOCs associated with SCD. Both studies are enrolling individuals with SCD ages 12 years and older who have experienced between two and 10 VOCs in the previous year. Inclacumab selectively targets P-selectin, a protein that mediates cell adhesion and is clinically validated to reduce pain crises. The first registrational trial is evaluating the effect of inclacumab on the frequency of VOCs. The second registrational trial is evaluating the effect of a single dose of inclacumab on hospital readmission rates.

A phase 1 study of six SCD patients demonstrated that GBT601, which has the same mechanism of action as Oxbryta, achieved a high target hemoglobin occupancy at daily doses lower than 500 mg, while maintaining a favorable safety and tolerability profile. After patients who participated in the earlier phase 1 study of GBT601 expressed interest in participating in a restart of the study at a higher dose, GBT recently restarted the phase 1 study to assess a 150 mg daily dose, greater than the 100 mg daily maintenance dose previously studied. Upon completion, the company plans to submit these new data for presentation at a medical meeting later this year.

The FDA’s Orphan drug designation provides orphan status to drugs and biologics that are being developed to address rare diseases or disorders that affect fewer than 200,000 people in the U.S. Orphan drug designation qualifies GBT for various incentives, including tax credits for qualified clinical trials and market exclusivity if it receives FDA approval.

A Rare Pediatric Disease designation is granted for rare diseases that primarily affect children under 18 years old, with recipients of this designation qualifying for a priority review voucher if the drug is approved and certain conditions are met. The priority review voucher may be redeemed, transferred, or sold. Recently, BridgeBio Pharma sold its priority review voucher for $110 million.

Author: Rare Daily Staff