Fulcrum Therapeutics Announces Positive Phase 1b Results for Pociredir in Sickle Cell Disease

Analysis reveals significant industry trends and economic implications

Release Date

2025-07-29

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Fulcrum Therapeutics reported positive results from the 12 mg dose cohort of its Phase 1b PIONEER trial of pociredir in sickle cell disease (SCD). The trial showed a robust 8.6% mean absolute increase in fetal hemoglobin (HbF) from baseline at 12 weeks, with seven of 16 patients achieving HbF levels over 20%. This was accompanied by improvements in markers of hemolysis and anemia, and an encouraging trend in vaso-occlusive crisis (VOC) reduction. Pociredir was generally well-tolerated with no treatment-related serious adverse events.

Key Highlights

  • 8.6% mean absolute increase in fetal hemoglobin (HbF) from baseline at 12 weeks in the 12 mg dose cohort.
  • Seven of 16 patients achieved HbF levels greater than 20%.
  • Improvements in markers of hemolysis and anemia.
  • Encouraging trend in vaso-occlusive crisis (VOC) reduction.

Economic Burden

Economic Burden of Treating Sickle Cell Disease in USA and Europe

United States

The economic burden of treating Sickle Cell Disease (SCD) in the USA is substantial, affecting approximately 100,000 individuals, primarily of African-American descent. Recent studies provide detailed estimates of this burden:

  • The annual medical cost of SCD is estimated at $3 billion in the United States.
  • A 2023 study reported an estimated annual indirect economic burden of $2,266,873 ($9,290 per participant) for SCD patients.

  • For Medicaid patients with SCD, the adjusted mean annual costs were significantly higher for those with end-organ damage (EOD):

  • $285,816 within 1 year after stroke

  • $127,393 more than 1 year after stroke

  • $135,493 for chronic kidney disease (CKD)

  • $209,172 for end-stage renal disease (ESRD)

  • $148,174 for pulmonary hypertension (PH)

Patients with multiple SCD complications faced even higher costs. The mean annual time patients spent receiving health care services ranged from 56 to 62 days for those with EOD versus 21 to 25 days for those without.

A 2009 study suggested a discounted lifetime cost of care averaging $460,151 per patient with SCD (using 3% discount rate). Total health care costs generally rose with age, from $892 to $2,562 per patient-month in the 0-9 and 50-64-year age groups, respectively, with an average cost per patient-month of $1,389.

Overall, 51.8% of care was directly related to SCD, with the majority (80.5%) associated with inpatient hospitalizations.

A 2024 systematic review found that costs were higher for SCD patients compared with non-SCD individuals, with an annual cost difference range of $6,636-$63,436. The highest medical cost component was inpatient care ($11,978-$59,851 annually).

For gene therapy, a 2022 budget impact analysis estimated that 5,464 Medicaid enrollees would be eligible nationally. With the therapy priced at $1.85 million in the base case and baseline disease-related expenditures at $42,200 per year, the projected mean 1-year budget impact was $29.96 million per state Medicaid program ($1.91 per member per month).

Europe

In Greece, the annual cost of sickle cell disease was estimated to be €21,152,340.00 (US$25,219,300.41), excluding the cost of hospitalization for severe complications. This represents approximately 1.0% of the budget allocated to pharmaceutical spending in Greece. This study was the first attempt to calculate the total annual cost of treating sickle cell disease patients in a steady state in Greece.

Additional Considerations

Both adults with SCD and caregivers of children with SCD commonly report employment loss and missed days of work, contributing to the indirect economic burden. Interventions designed to prevent SCD complications and avoid hospitalizations may reduce the significant economic burden of the disease.

Recent Studies

Recent Sickle Cell Disease Studies

Gazelle Study (2021)

This study evaluated a microchip-based cellulose acetate electrophoresis test called "Gazelle" in tribal-dominated Indian states. The study screened 1,050 patients using multiple methods including HPLC. Key outcomes showed that Gazelle identified all patients with disease (HbSS and Thalassemia Major) with 100% accuracy, demonstrated 100% sensitivity when comparing sickle cell disease (SCD) vs. sickle cell trait and SCD vs. normal, and achieved 99.0% overall accuracy compared to reference standard tests. Gazelle proved to be a low-cost, rapid diagnostic test with high accuracy for detecting SCD, making it suitable for resource-limited settings.

IMPROVE II Study (2023)

This study focused on characterizing the relationship between plasma free hemoglobin (PFH) and other hemolytic markers in 68 adult patients with HbSS or HbSβ-thalassemia. Key findings revealed that PFH had strong correlations with LDH (R = 0.699), AST (R = 0.587), and total bilirubin (R = 0.475). A composite hemolysis score derived from principal component analysis was significantly associated with PFH (R = 0.677) and with WBC, hemoglobin, HbF, and HbS. The study concluded that conventional hemolytic biomarkers correlate with PFH, and the hemolysis score is a valid tool for measuring global hemolysis.

STAND Study

This phase 3, multicentre, randomised, double-blind study evaluated crizanlizumab in patients with sickle cell disease aged 12 years and older across 65 sites in 21 countries. Patients were randomly assigned to receive either 5.0 mg/kg of crizanlizumab, 7.5 mg/kg of crizanlizumab, or placebo in addition to standard of care for 1 year. The primary endpoint was the annualised rate of vaso-occlusive crises leading to a health-care visit. Between July 2019 and August 2022, 252 patients were enrolled and treated. The primary analysis showed no significant difference in efficacy between crizanlizumab and placebo, contrasting with the earlier SUSTAIN study which had shown a reduction of vaso-occlusive crises in patients treated with crizanlizumab.

Crizanlizumab Retrospective Analysis

A retrospective analysis of patients who received crizanlizumab at a dose of 5 mg/kg between July 2020 and January 2022 found that the average number of acute care visits decreased following crizanlizumab initiation but was not statistically significant (20 visits vs. 10 visits, P = 0.07). However, among high users of hospital-based services, the average number of acute care visits decreased significantly after initiation (40 vs. 16, P = 0.005). The study noted a very high discontinuation rate, with only five patients remaining on crizanlizumab 6 months after initiation.

Drug used in other indications

Pociredir Clinical Trials Beyond Sickle Cell Disease

After a comprehensive review of available information, I cannot provide details about additional indications for which Pociredir is being trialed beyond sickle cell disease. The requested information about alternative therapeutic applications and intervention models for Pociredir in non-sickle cell disease trials is not available.

Clinical trials typically employ various intervention models such as parallel group, crossover designs, factorial assignments, or sequential assignments, each with specific protocols tailored to the medication and condition being studied. However, specific information about Pociredir's trial methodologies in other indications cannot be determined.

For patients interested in emerging treatments, consulting with healthcare providers or referring to official clinical trial registries such as ClinicalTrials.gov would provide the most current and accurate information about Pociredir and its potential applications beyond sickle cell disease.

Pharmaceutical development often explores multiple potential indications for promising compounds, with rigorous testing required before approval for each specific use. The regulatory pathway typically involves progression through Phase I (safety), Phase II (efficacy), and Phase III (comparative effectiveness) trials before consideration for market approval.