osivelotor (PF-07940367) / Pfizer - LARVOL DELTA

Impact of novel mobilizers and disease modifying agents in the sickle mouse (ASGCT 2025) - "The novel mobilizing agent EMU116 increases stem cells with long term potential (LSKLin-) and primitive HSCs able to rapidly reconstitute (%Flt3-CD34-) in the PB of HbSS and HbAA mice significantly more than plerixafor. CFU are also higher with mobilization indicating stem cells able to proliferate and differentiate, although not statistically significant likely due to sample size. SCD modification with anti-sickling drug osivelotor increased plerixafor mobilization of %Flt3-CD34- HSCs."

Preclinical • Gene Therapies • Genetic Disorders • Hematological Disorders • Inflammation • Sickle Cell Disease • CD34 • CXCR4 • FLT3

PHASE 1 STUDY OF RENAL IMPAIRMENT EFFECTS ON THE PHARMACOKINETICS OF OSIVELOTOR, A SMALL MOLECULE IN DEVELOPMENT FOR SICKLE CELL DISEASE (EHA 2025) - P1 | "Using a popPK/PD-informed approach, this study demonstrated severe RI did not have clinically meaningful effects on osivelotor exposure, and whole blood exposure was generally within the PK variability observed in patients with SCD. Additionally, differences in plasma exposure in severe RI compared with a simulated healthy population were marginal. A single 400 mg dose in participants with severe RI but without SCD was generally well tolerated, with no treatment-related TEAEs."

P1 data • PK/PD data • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Renal Disease • Respiratory Diseases • Sickle Cell Disease

PRELIMINARY PHARMACODYNAMIC BIOMARKER RESULTS IN PATIENTS WITH SICKLE CELL DISEASE FOLLOWING TREATMENT WITH OSIVELOTOR IN A MULTICENTER PHASE 2/3 TRIAL (EHA 2025) - P2/3 | "These preliminary PD results from patients with SCD suggest promising evidence of improved RBC health and blood flow following osivelotor treatment. Overall, the findings support ongoing clinical development of osivelotor as a potential treatment for individuals with SCD."

Biomarker • Clinical • P2/3 data • PK/PD data • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • VCAM1

Use of the Microfluidic Impedance Red Cell Assay (MIRCA) in Sickle Cell Disease. (PubMed, Blood Adv) - "In vitro addition of voxelotor or osivelotor to samples from individuals on CTF improved the deformability of these endogenous RBC. Longitudinally collected NOI and HOI values in HbSS individuals were stable, with a median percent point change of 13.3% and 15.7%, respectively. MIRCA can be used in combination with clinical laboratory tests to monitor RBC deformability as a biomarker of clinical status at routine clinic visits and included in clinical trials of disease modifying agents."

Journal • Cardiovascular • Genetic Disorders • Hematological Disorders • Inflammation • Pain • Pediatrics • Sickle Cell Disease

GBT021601-022: A Study of GBT021601 in Participants With Sickle Cell Disease (SCD) (clinicaltrials.gov) - P2/3 | N=47 | Terminated | Sponsor: Pfizer | Active, not recruiting ➔ Terminated; Study terminated as data obtained from this non-placebo-controlled trial may not be informative for the interpretation of the benefits and risks of osivelotor

Trial termination • Genetic Disorders • Hematological Disorders • 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: Oct 2025 ➔ Oct 2026 | Initiation date: Mar 2025 ➔ Apr 2026 | Trial primary completion date: Oct 2025 ➔ Oct 2026

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

Osivelotor for the treatment of sickle cell disease. (PubMed, Expert Opin Pharmacother) - "However, osivelotor shares the same mechanism of action as voxelotor, and therefore similar limitations regarding its efficacy for which the improvement in Hb level appears misleading. Several issues remain to be resolved before considering any drug approval."

Journal • Review • Genetic Disorders • Hematological Disorders • 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=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