osivelotor (PF-07940367) / Pfizer - LARVOL DELTA

A Study to Learn How the Body Processes the Study Medicine Called Osivelotor (PF-07940367) in People With Loss of Liver Function (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed | N=16 ➔ 8 | Trial completion date: Jun 2025 ➔ Sep 2024 | Trial primary completion date: Jun 2025 ➔ Sep 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Hepatology

Long-Term Therapy with GBT021601 and Moderate Chronic Transfusion Therapy Prevent the Development of Hyperalgesia (ASH 2024) - "More importantly, an oral agent 601 equally reduces development of chronic pain as early as 4 weeks of therapy in the sickle mouse model. Pain phenotypes should be further investigated with 601 in the prevention of chronic pain in clinical studies."

Cardiovascular • Genetic Disorders • Hematological Disorders • Musculoskeletal Pain • Pain • Sickle Cell Disease

Methods to Assess the Impact of Combined Pharmacologic and Transfusion Therapies on Red Cell Deformability (ASH 2024) - "GBT021601-modified red cells had similar MIRCA deformability values to healthy controls; we expect to see a similar benefit in patients on dual transfusion and drug therapy. Future work will involve the use of MIRCA to assess the longitudinal variability of RBC deformability in individuals on chronic transfusion therapy alone and in combination with anti-sickling agents, to determine if transfusions can be reduced in frequency and volume without sacrificing RBC quality."

Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

GBT021601-022: A Study of GBT021601 in Participants With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P2/3 | N=47 | Active, not recruiting | Sponsor: Pfizer | N=13 ➔ 47

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

GBT021601-022: A Study of GBT021601 in Participants With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P2/3 | N=13 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=314 ➔ 13 | Trial completion date: Apr 2029 ➔ Jan 2025 | Trial primary completion date: Apr 2029 ➔ Jan 2025

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

Editor's Note to the letter 'Therapeutic potential of the latest oxygen affinity modifying agent, GBT021601, for treating sickle cell disease is questionable' by Drs. Eaton, Alaimo, Metaferia, Cellmer, Thein and Bunn. (PubMed, Br J Haematol) - No abstract available

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Therapeutic potential of the latest oxygen affinity-modifying agent, GBT021601, for treating sickle cell disease is questionable. (PubMed, Br J Haematol) - No abstract available

Journal • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

GBT021601-021: A Phase 2/3 Study in Adult and Pediatric Participants With SCD (clinicaltrials.gov) - P2/3 | N=429 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

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

A Study to Learn How Different Preparations of Osivelotor Taste and Enter the Blood With Food or Liquids or With an Antacid in Healthy Adults (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: Pfizer | Trial completion date: Feb 2025 ➔ Oct 2025 | Initiation date: Aug 2024 ➔ Mar 2025 | Trial primary completion date: Feb 2025 ➔ Oct 2025

Trial completion date • Trial initiation date • Trial primary completion date • Pediatrics

GBT021601-021: A Phase 2/3 Study in Adult and Pediatric Participants With SCD (clinicaltrials.gov) - P2/3 | N=517 | Recruiting | Sponsor: Pfizer | Trial completion date: Oct 2026 ➔ Oct 2028 | Trial primary completion date: Oct 2026 ➔ Oct 2028

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

Study of GBT021601 in Participants With Renal Impairment (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Pfizer | N=40 ➔ 4 | Recruiting ➔ Terminated; Business decision to terminate the trial after the completion of Part 1: Cohort 1 (severe renal impairment). The decision to terminate the trial was not due to any potential safety concerns.

Enrollment change • Trial termination • Renal Disease

A Study to Learn How the Body Processes the Study Medicine Called Osivelotor (PF-07940367) in People With Loss of Liver Function (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Pfizer | Trial completion date: Sep 2025 ➔ Jun 2025 | Trial primary completion date: Sep 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Hepatology

A Study to Learn How Different Preparations of Osivelotor Taste and Enter the Blood With Food or Liquids or With an Antacid in Healthy Adults. (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: Pfizer

New P1 trial • Pediatrics

PRELIMINARY RESULTS FROM A MULTICENTER PHASE 2/3 STUDY OF NEXT-GENERATION HBS POLYMERIZATION INHIBITOR OSIVELOTOR (GBT021601) FOR THE TREATMENT OF PATIENTS WITH SICKLE CELL DISEASE (EHA 2024) - P2/3 | "7 (18–59) y, 32/35 pts were HbSS, and 16/35 wereon stable hydroxyurea at BL. In preliminary results from Part A of this phase 2/3 study, loading and daily doses of osivelotor for 12 weekswere well tolerated in adults with SCD. Results to date show large increases in mean Hb accompanied byimprovements in markers of hemolysis. Although oxygen delivery was not directly measured, no impairmentwas suggested by indicators of oxygen delivery (i."

Clinical • P2/3 data • Cardiovascular • CNS Disorders • Dermatology • Epilepsy • Genetic Disorders • Hematological Disorders • Immunology • Pain • Sickle Cell Disease • Urticaria

A Study to Learn How Different Products of the Study Medicine Called PF-07940367 Are Taken up Into the Blood in Healthy Adults (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed | N=60 ➔ 40 | Trial completion date: Aug 2024 ➔ May 2024 | Trial primary completion date: Aug 2024 ➔ May 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date

A Study to Learn How the Body Processes the Study Medicine Called Osivelotor (PF-07940367) in People With Loss of Liver Function (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

A Study to Learn How the Body Processes the Study Medicine Called Osivelotor (PF-07940367) in People With Loss of Liver Function (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Pfizer | Trial completion date: Feb 2026 ➔ Sep 2025 | Trial primary completion date: Feb 2026 ➔ Sep 2025

Trial completion date • Trial primary completion date • Hepatology

GBT021601-022: A Study of GBT021601 in Participants With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P2/3 | N=314 | Recruiting | Sponsor: Pfizer | Enrolling by invitation ➔ Recruiting | N=500 ➔ 314

Enrollment change • Enrollment status • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

GBT021601-021: A Phase 2/3 Study in Adult and Pediatric Participants With SCD (clinicaltrials.gov) - P2/3 | N=517 | Recruiting | Sponsor: Pfizer | Trial completion date: Jun 2026 ➔ Oct 2026 | Trial primary completion date: Jun 2026 ➔ Oct 2026

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

A Study to Learn How the Body Processes the Study Medicine Called Osivelotor (PF-07940367) in People With Loss of Liver Function (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Pfizer

New P1 trial • Hepatology

A Study to Learn How Different Products of the Study Medicine Called PF-07940367 Are Taken up Into the Blood in Healthy Adults (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Pfizer | N=154 ➔ 60

Enrollment change

A Study to Learn How Different Products of the Study Medicine Called PF-07940367 Are Taken up Into the Blood in Healthy Adults (clinicaltrials.gov) - P1 | N=154 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Learn How Different Products of the Study Medicine Called PF-07940367 Are Taken up Into the Blood in Healthy Adults (clinicaltrials.gov) - P1 | N=154 | Not yet recruiting | Sponsor: Pfizer

New P1 trial

Predictive Biomarker Analysis from the GBT021601 Survival Study in Townes Sickle Mice (ASH 2023) - "Longer-term GBT021601 treatment as part of chow was well tolerated by Townes SS mice, and compound exposure was comparable with studies of a shorter duration of treatment. Early compound exposure was predictive of a long-term survival benefit in Townes SS mice. Early reductions in % reticulocytes were more likely in Townes SS mice with a high GBT021601 exposure and were predictive of a long-term survival benefit."

Preclinical • Anemia • Cardiovascular • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Preliminary Results from a Multicenter Phase 2/3 Study of Next-Generation HbS Polymerization Inhibitor GBT021601 for the Treatment of Patients with Sickle Cell Disease (ASH 2023) - P2/3 | "GBT021601 has the potential for higher Hb occupancies at lower doses than voxelotor and could potentially reduce treatment burden and improve clinical outcomes...The 100-mg group consisted of 17/35 patients (48.6%), with a mean (range) age of 29.1 (18-49) years; 7/17 patients (41.2%) were on hydroxyurea (HU)... Loading and daily doses of GBT021601 for 12 weeks were well tolerated in adult participants with SCD. Despite large increases in mean Hb levels, pain episodes did not increase and there was a reduction of adherent cells in a flow adhesion assay with VCAM-1, a potential biomarker for VOC risk. Data from Part A of this phase 2/3 study support the ongoing clinical development of GBT021601 as a potential treatment for individuals with SCD."

Clinical • P2/3 data • Anemia • CNS Disorders • Dermatology • Epilepsy • Genetic Disorders • Hematological Disorders • Immunology • Infectious Disease • Pain • Pediatrics • Septic Shock • Sickle Cell Disease • Urticaria • VCAM1