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BMS-986470

BMS-986470 is a new investigational drug currently being studied for its potential benefits in treating sickle cell disease. This article explores an ongoing Phase 1/2a clinical trial that evaluates this drug in both healthy volunteers and patients with sickle cell disease. The research aims to determine the safety, tolerability, and preliminary effectiveness of BMS-986470, while also studying how the body processes the medication under different conditions. This first-in-human study represents an important step in developing new treatment options for those affected by sickle cell disease.

Table of Contents

What is BMS-986470?

BMS-986470 is an investigational medication that is being developed for the treatment of sickle cell disease. It is currently in early stages of clinical development (Phase 1/2a trials) which means researchers are studying its safety, how it moves through the body, and whether it might be effective in treating sickle cell disease[1].

Study Overview

This drug is being evaluated in a “first-in-human” clinical trial, which means this is one of the earliest studies testing this medication in people. The study is designed as a randomized, double-blinded, placebo-controlled, dose-finding study. These terms mean:

  • Randomized: Participants are assigned by chance to either receive the actual drug or a placebo (a substance with no active ingredients)
  • Double-blinded: Neither the participants nor the researchers know who is receiving the actual drug or placebo
  • Placebo-controlled: Some participants receive a placebo to help determine if the drug’s effects are real
  • Dose-finding: Different amounts of the drug are tested to find the most appropriate dose[1]

The study includes both healthy volunteers and patients with sickle cell disease. This approach is common in early drug development to first establish safety in healthy people before testing in patients with the condition[1].

Target Conditions: Sickle Cell Disease

Sickle cell disease is an inherited blood disorder that affects the shape of red blood cells. In this condition, red blood cells become shaped like crescents or sickles instead of the normal disc shape. These abnormally shaped cells can get stuck in small blood vessels, causing pain, organ damage, and other serious complications. The disease also causes hemolytic anemia, a condition where red blood cells break down prematurely[1].

A key feature of the disease is the presence of sickle hemoglobin (HbS), which is different from normal adult hemoglobin (HbA). Hemoglobin is the protein in red blood cells that carries oxygen. Another type of hemoglobin, fetal hemoglobin (HbF), is normally produced during fetal development but production decreases after birth. Increasing HbF levels can help reduce symptoms in sickle cell disease patients[1].

How the Drug Works

While the exact mechanism of BMS-986470 isn’t explicitly stated in the study information, the study’s measures suggest that the drug may work by affecting hemoglobin production. Specifically, one of the goals appears to be increasing the production of fetal hemoglobin (HbF). This is an important potential treatment approach because fetal hemoglobin can prevent or reduce the sickling of red blood cells that occurs with sickle hemoglobin (HbS)[1].

The study is measuring changes in different hemoglobin types, including HbF, HbA, and HbS, which suggests that the drug may alter the balance of these hemoglobins in the body[1].

Safety and Monitoring

As with all experimental medications, safety is a primary concern. The study is carefully monitoring for:

  • Adverse events (AEs): Any undesirable experience that occurs during the study
  • Serious adverse events (SAEs): Events that may be life-threatening or require hospitalization
  • Dose Limiting Toxicity (DLT): Side effects serious enough to prevent increasing the dose further
  • Events leading to discontinuation of the treatment
  • Any deaths that occur during the study[1]

The study is also examining how the drug moves through the body (pharmacokinetics) and how it affects the body (pharmacodynamics). Researchers are also looking at how food and stomach pH (acidity) might affect how the drug works[1].

Effectiveness Measures

To determine if BMS-986470 might be effective for sickle cell disease, researchers are measuring several indicators:

  1. Hemoglobin levels: Checking if total hemoglobin increases, which could improve oxygen delivery to tissues
  2. Hemoglobin fractions: Measuring changes in different types of hemoglobin (HbA, HbF, HbS)
  3. Red blood cell (RBC) lysis markers: Monitoring indicators that show whether red blood cells are breaking down less frequently, including:
    • Aspartate aminotransferase (AST): An enzyme that increases when cells are damaged
    • Lactate dehydrogenase (LDH): Another enzyme that increases with cell damage
    • Bilirubin: A yellowish substance produced when red blood cells break down
    • Haptoglobin: A protein that binds to hemoglobin released from damaged red blood cells
    • Reticulocyte count: Immature red blood cells; high counts can indicate the body is trying to compensate for anemia
    • Schistocyte count: Fragmented red blood cells that can indicate damage[1]

The study is particularly interested in how many participants achieve specific HbF levels (10%, 20%, or 30% or more). Higher levels of HbF are generally associated with less severe sickle cell disease symptoms[1].

Potential Benefits for Patients

If successful, BMS-986470 could potentially offer several benefits for sickle cell disease patients:

  • Increased fetal hemoglobin: By potentially increasing HbF levels, the drug might reduce the sickling of red blood cells
  • Reduced cell destruction: Less breaking down of red blood cells could mean less anemia and fewer complications
  • Improved hemoglobin levels: Higher total hemoglobin could improve oxygen delivery throughout the body
  • Fewer pain crises: With less sickling and vessel blockage, patients might experience fewer painful episodes[1]

It’s important to note that since this is an early-phase clinical trial, the effectiveness of BMS-986470 is still being investigated, and it may be several years before the drug could potentially become available as an approved treatment[1].

Category Details
Study Type Phase 1/2a, first-in-human, randomized, double-blinded, placebo-controlled, dose-finding study
Study Population Healthy volunteers and participants with sickle cell disease
Drug Being Tested BMS-986470 (multiple dosing regimens)
Primary Outcomes Safety measures: adverse events, serious adverse events, dose-limiting toxicities, discontinuations, deaths
Key Secondary Outcomes • Pharmacokinetic parameters (Cmax, AUC, Tmax)
• Changes in total hemoglobin and hemoglobin fractions (HbA, HbF, HbS)
• Markers of red blood cell destruction
• Number of participants achieving significant HbF increases (≥10%, ≥20%, ≥30%)
Study Design • Multiple cohorts of participants
• Cohort A: Parts 1 and 2 (likely dose escalation)
• Cohort B: Parts 1 and 2 (likely extension or specific patient groups)
• Includes pH and food effect evaluation

FAQ

  • What is BMS-986470? BMS-986470 is an investigational drug being studied for its potential to help people with sickle cell disease. It's currently in early clinical trials (Phase 1/2a), and researchers are evaluating its safety, how it works in the body, and whether it might be effective for treating sickle cell disease.
  • What is the purpose of this clinical trial? The purpose of this trial is to evaluate several aspects of BMS-986470: its safety and tolerability in both healthy volunteers and people with sickle cell disease, how the drug moves through and is processed by the body (pharmacokinetics), how it affects the body (pharmacodynamics), how food and stomach pH might affect it, and preliminary evidence of whether it works for sickle cell disease.
  • Who can participate in this clinical trial? The trial includes both healthy volunteers and participants with sickle cell disease. These two groups are studied separately to understand how the drug affects people with and without the condition. The specific eligibility criteria would be determined by the research team based on safety considerations and research objectives.
  • What outcomes are researchers measuring in this trial? Researchers are primarily measuring safety outcomes, such as the number of participants experiencing side effects, serious adverse events, or other safety concerns. They're also looking at how the drug moves through the body and, importantly for sickle cell patients, changes in total hemoglobin levels and different hemoglobin types (especially fetal hemoglobin or HbF), as well as markers of red blood cell breakdown.
  • Why is the measurement of fetal hemoglobin (HbF) important in this study? Increasing fetal hemoglobin (HbF) is an important treatment strategy for sickle cell disease. The study measures whether BMS-986470 can help patients achieve HbF levels of 10%, 20%, or 30% or higher. Higher levels of HbF can prevent red blood cells from sickling and may reduce complications of the disease. The researchers are specifically tracking how many participants reach these beneficial HbF targets.

Ongoing Clinical Trials on BMS-986470

  • Study on the Safety and Effects of BMS-986470 for Patients with Sickle Cell Disease

    Recruiting

    1
    Investigated diseases:
    Investigated drugs:
    France

Glossary

  • Sickle Cell Disease: A group of inherited red blood cell disorders where abnormal hemoglobin causes red blood cells to become sickle or crescent-shaped, leading to blockages in blood vessels, pain, and organ damage.
  • Phase 1/2a Trial: An early stage clinical trial that combines initial safety testing (Phase 1) with preliminary effectiveness testing (Phase 2a) of a new drug or treatment.
  • First-in-human: The first time a new drug or treatment is tested in human subjects after laboratory and animal testing.
  • Pharmacokinetics: The study of how a drug moves through the body, including how it's absorbed, distributed, metabolized, and eliminated.
  • Pharmacodynamics: The study of how a drug affects the body, including its mechanisms of action and the relationship between drug concentration and effect.
  • Double-blinded: A study design where neither the participants nor the researchers know who is receiving the actual drug versus placebo until after the study is completed.
  • Placebo-controlled: A study design where some participants receive an inactive substance (placebo) instead of the drug being tested to help determine if the drug's effects are real.
  • Adverse Events (AEs): Any unfavorable or unintended sign, symptom, or disease that occurs during a clinical trial, whether or not it's caused by the treatment being studied.
  • Serious Adverse Events (SAEs): Adverse events that result in death, are life-threatening, require hospitalization, cause persistent disability, or have other significant medical consequences.
  • Dose Limiting Toxicity (DLT): Side effects that are severe enough to prevent increasing the dose of a drug during a clinical trial.
  • Hemoglobin (Hb): The protein in red blood cells that carries oxygen throughout the body. In sickle cell disease, abnormal hemoglobin (HbS) causes problems.
  • Fetal Hemoglobin (HbF): A type of hemoglobin normally produced during fetal development that can help prevent sickling of red blood cells. Increasing HbF is a treatment strategy for sickle cell disease.
  • Adult Hemoglobin (HbA): The normal type of hemoglobin found in adults, which replaces fetal hemoglobin after birth.
  • Sickle Hemoglobin (HbS): The abnormal form of hemoglobin found in people with sickle cell disease that causes red blood cells to become sickle-shaped.
  • Red Blood Cell (RBC) Lysis: The breaking open and destruction of red blood cells, which occurs at a higher rate in sickle cell disease and can cause anemia and other complications.
  • Reticulocyte: Immature red blood cells released from the bone marrow. High levels often indicate the body is trying to compensate for anemia or red blood cell destruction.
  • Schistocyte: Fragmented red blood cells that indicate damage to red blood cells, which can occur in sickle cell disease.
  • Haptoglobin: A protein that binds to free hemoglobin in the blood. Low levels may indicate increased red blood cell breakdown.
  • Lactate Dehydrogenase (LDH): An enzyme released when cells are damaged. Elevated levels can indicate red blood cell destruction.
  • Bilirubin: A yellowish substance produced when red blood cells break down. High levels can indicate increased red blood cell destruction and may cause jaundice.

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