etavopivat (NN7535) / Novo Nordisk - LARVOL DELTA

HIBISCUS 3: A Phase 2 Open-label Study to Evaluate the Activity of Etavopivat on Transcranial Doppler Velocities in Pediatric Patients With Sickle Cell Disease Who Are at Increased Risk for Primary Stroke (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: Forma Therapeutics, Inc. | N=46 ➔ 27 | Trial completion date: May 2026 ➔ Sep 2027 | Trial primary completion date: Jul 2025 ➔ Sep 2027

Enrollment change • Trial completion date • Trial primary completion date • Cardiovascular • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

A Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients With Sickle Cell Disease (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Forma Therapeutics, Inc. | Trial primary completion date: Feb 2029 ➔ Aug 2029

Trial primary completion date • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

A Study on the Effect of Etavopivat on Heart Rhythm in Healthy Participants (clinicaltrials.gov) - P1 | N=26 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P1 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

GLADIOLUS: A Study of Etavopivat in Patients With Thalassemia or Sickle Cell Disease (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Forma Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

FLORAL: A Research Study Looking at Long-term Treatment With Etavopivat in People With Sickle Cell Disease or Thalassaemia (clinicaltrials.gov) - P3 | N=325 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Research Study of the Effect of Etavopivat on Other Drugs in Healthy Participants (clinicaltrials.gov) - P1 | N=29 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS) (clinicaltrials.gov) - P3 | N=450 | Active, not recruiting | Sponsor: Forma Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Hibiscus 2: A Research Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=408 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS) (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Forma Therapeutics, Inc. | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial primary completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Research Study of the Effect of Etavopivat on Other Drugs in Healthy Participants (clinicaltrials.gov) - P1 | N=29 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P1 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study of Etavopivat in Adults and Adolescents With Sickle Cell Disease (HIBISCUS) (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Forma Therapeutics, Inc. | Phase classification: P2/3 ➔ P3 | N=344 ➔ 450 | Trial primary completion date: Mar 2026 ➔ Mar 2025

Enrollment change • Phase classification • Trial primary completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients With Sickle Cell Disease (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Forma Therapeutics, Inc. | Phase classification: P1/2 ➔ P2

Phase classification • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

Etavopivat Reduces Incidence of Vaso-Occlusive Crises in Patients with Sickle Cell Disease: HIBISCUS Trial Phase 2 Results through 52 Weeks (ASH 2024) - P2/3 | "Permitted standard of care included stable dosing with hydroxyurea (HU; ≥90 days prior), crizanlizumab, or L-glutamine (≥12 months prior). Etavopivat was well tolerated. Based on the totality of data, proof of concept was established for etavopivat in SCD."

Clinical • P2 data • Cardiovascular • CNS Disorders • Fatigue • Genetic Disorders • Hematological Disorders • Insomnia • Sickle Cell Disease • Sleep Disorder

A Research Study Looking at a Single Dose of Etavopivat in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Novo Nordisk A/S | Recruiting ➔ Completed

Trial completion • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Etavopivat Increases Arterial Hemoglobin-Oxygen Saturation during Moderate and Severe Hypoxia: A Mechanistic Phase 1 Trial in Healthy Volunteers (ASH 2024) - "Increased Hb-O2 affinity, together with maintenance of a high FO2Hb under hypoxic conditions, demonstrates etavopivat's ability to promote oxygen exchange and subsequent delivery. Together with projected improvement of RBC health, also achieved via PKR activation, this indicates a potential clinical benefit with etavopivat for hemoglobinopathies and beyond."

Clinical • P1 data • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Hospital Utilization in Sickle Cell Disease Patients: A One-Year Retrospective Study in Urban Underserved Communities (ASH 2024) - "The average age was 20.3 years.Black patients, compared to Hispanic patients, had more ED visits (13.5 vs 4.6, p=0.101), more readmissions (4.2 vs 2.4, p=0.052), and longer LOS (5.3 vs 3.0 days, p=0.267).Regarding medication use, 78.6% of patients (N=24) were taking Hydroxyurea, 3.6% (N=1) were receiving Voxelotor, and 7.1% (N=2) were enrolled in the clinical trial (Etavopivat). Lack of regular hematologist follow-up and presence of psychiatric disorders were associated with increased healthcare utilization. These findings emphasize the need for improved access to hematology follow-up and integrated psychiatric care, to enhance the quality of life for SCD patients."

Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Genetic Disorders • Hematological Disorders • Mental Retardation • Mood Disorders • Pain • Psychiatry • Sickle Cell Disease

Pyruvate Kinase Activators in Sickle Cell Anemia: A Systematic Review and Single-Arm Meta-Analysis (ASH 2024) - "Three studies administered Mitapivat (n=76), and one administered Etavopivat (n=23). However, the small sample size, observed heterogeneity, and variations in concurrent hydroxyurea use highlight the need for larger, comparative trials to confirm these findings and assess PK activators relative to existing treatments. Future research should focus on more extensive and homogeneous cohorts to validate these results and investigate long-term outcomes."

Retrospective data • Review • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

FT-4202, a selective pyruvate kinase R activator for sickle cell disease. (PubMed, Exp Hematol) - "There were no adverse in vitro safety findings. FT-4202 offers a therapeutic opportunity to modify the course of SCD."

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

HIBISCUS 3: A Phase 2 Open-label Study to Evaluate the Activity of Etavopivat on Transcranial Doppler Velocities in Pediatric Patients With Sickle Cell Disease Who Are at Increased Risk for Primary Stroke (clinicaltrials.gov) - P2 | N=46 | Recruiting | Sponsor: Forma Therapeutics, Inc. | Trial completion date: Oct 2026 ➔ May 2026

Trial completion date • Cardiovascular • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

Hibiscus 2: A Research Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=408 | Not yet recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: Dec 2025 ➔ Aug 2027

Trial primary completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

NN7535-7702: A Research Study of the Effect of Food on Etavopivat in Healthy Participants (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Novo Nordisk A/S | Recruiting ➔ Completed

Trial completion • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Study of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Forma Therapeutics, Inc. | Trial completion date: Aug 2025 ➔ Feb 2026

Trial completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Hibiscus 2: A Research Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease (clinicaltrials.gov) - P3 | N=408 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients With Sickle Cell Disease (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Forma Therapeutics, Inc. | Trial completion date: Jan 2026 ➔ Jun 2029 | Trial primary completion date: Jan 2026 ➔ Feb 2029

Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Pediatrics • Sickle Cell Disease

FLORAL: A Research Study Looking at Long-term Treatment With Etavopivat in People With Sickle Cell Disease or Thalassaemia (clinicaltrials.gov) - P3 | N=325 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease