lotiglipron (PF-07081532) / Pfizer, Nxera Pharma - LARVOL DELTA

Evaluation of an oral small-molecule glucagon-like peptide-1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose-ranging, phase 2, randomized, placebo-controlled study. (PubMed, Diabetes Obes Metab) - P2 | "The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at-risk population unsuccessful and therefore clinical development of lotiglipron terminated."

Clinical • Journal • P2 data • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Once-daily oral small-molecule glucagon-like peptide-1 receptor agonist lotiglipron (PF-07081532) for type 2 diabetes and obesity: Two randomized, placebo-controlled, multiple-ascending-dose Phase 1 studies. (PubMed, Diabetes Obes Metab) - P1 | "The profile of once-daily lotiglipron with doses up to 180 mg, as observed in these two Phase 1 studies, indicated a safety and tolerability profile consistent with the mechanism of action, with dose-dependent reductions in glycaemic indices (T2D) and body weight (both populations) after multiple doses."

Clinical • Journal • P1 data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study to Evaluate the Effect of the Experimental GLP-1 Drug PF-07081532 on Blood Levels of Common Birth Control Pills, and Drugs Omeprazole and Midazolam, and Effect of GLP-1 Drug Semaglutide on Midazolam Blood Levels in Healthy Adults With Weight in the Obesity Range (clinicaltrials.gov) - P1 | N=32 | Terminated | Sponsor: Pfizer | Completed ➔ Terminated; The decision to terminate clinical development of lotiglipron is based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as a Phase 2 study.

Trial termination • Genetic Disorders • Long-acting Reversible Contraceptives • Obesity

A Clinical Trial of the Study Medicine (PF-07081532) in People With Diabetes and Kidney Dysfunction (clinicaltrials.gov) - P1 | N=18 | Terminated | Sponsor: Pfizer | Completed ➔ Terminated; The decision to terminate clinical development of lotiglipron is based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as a Phase 2 study.

Trial termination • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

A Study to Evaluate the Effect of the Experimental GLP-1 Drug PF-07081532 on Blood Levels of Common Birth Control Pills, and Drugs Omeprazole and Midazolam, and Effect of GLP-1 Drug Semaglutide on Midazolam Blood Levels in Healthy Adults With Weight in the Obesity Range (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Long-acting Reversible Contraceptives • Obesity

Trial to Learn About the Study Medicine (PF-07081532) and Rybelsus in People With Type 2 Diabetes and Separately PF-07081532 in People With Obesity (clinicaltrials.gov) - P2 | N=902 | Terminated | Sponsor: Pfizer | Active, not recruiting ➔ Terminated; The decision to terminate clinical development of PF-07081532 is based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as a Phase 2 study.

Trial termination • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Drug-Drug Interaction Study to Estimate the Effect of PF-07081532 on the Pharmacokinetics of Dabigatran and Rosuvastatin in Overweight or Obese Adult Participants (clinicaltrials.gov) - P1 | N=16 | Terminated | Sponsor: Pfizer | Active, not recruiting ➔ Terminated; The decision to terminate clinical development of lotiglipron is based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as a Phase 2 study.

Trial termination • Obesity

Pfizer (PFE) plans to announce Danuglyprone Phase 2b clinical trial results at the end of the year…expected to secure at least a high single-digit market share [Google translation] (Infostock Daily) - "Danuglyprone (PF-07081532), Pfizer's only clinical-stage obesity treatment candidate, is scheduled to announce the results of phase 2b clinical trials at the end of the year. The final patient intervention for weight loss rate, the primary efficacy evaluation indicator, is expected to have already been completed in mid-September."

P2b data • Metabolic Disorders • Obesity

A Drug-Drug Interaction Study to Estimate the Effect of PF-07081532 on the Pharmacokinetics of Dabigatran and Rosuvastatin in Overweight or Obese Adult Participants (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Pfizer | N=24 ➔ 16

Enrollment change • Obesity

Sosei Heptares Operational Highlights and Consolidated Results for the Second Quarter and First Half of 2023 (Yahoo Finance) - "Pfizer announced its decision to prioritize the development of danuglipron over lotiglipron for the treatment of diabetes and obesity...as a result, Pfizer discontinued the development of lotiglipron, a novel and orally available GLP-1 receptor agonist discovered and developed by Pfizer during a multi-target research collaboration with Sosei Heptares. Sosei Heptares will explore next steps with Pfizer for the future development of lotiglipron."

Discontinued • Pipeline update • Diabetes • Fibrosis • Immunology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity • Type 2 Diabetes Mellitus

A Clinical Trial of the Study Medicine (PF-07081532) in People With Diabetes and Kidney Dysfunction (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Trial to Learn About the Study Medicine (PF-07081532) and Rybelsus in People With Type 2 Diabetes and Separately PF-07081532 in People With Obesity (clinicaltrials.gov) - P2 | N=902 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Dec 2023 ➔ Aug 2023 | Trial primary completion date: Nov 2023 ➔ Jun 2023

Trial completion date • Trial primary completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Clinical Trial of the Study Medicine (PF-07081532) in People With Diabetes and Kidney Dysfunction (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=32 ➔ 15

Enrollment change • Enrollment closed • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

A Drug-Drug Interaction Study to Estimate the Effect of PF-07081532 on the Pharmacokinetics of Dabigatran and Rosuvastatin in Overweight or Obese Adult Participants (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • Obesity

A Drug-Drug Interaction Study to Examine the Impact of Itraconazole and Cyclosporine on PF-07081532 Pharmacokinetics in Overweight or Obese Adults (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed

Trial completion • Obesity

Value of synthetic chemistry in medicinal chemistry: Discovery of PF-07081532, a small molecule GLP-1 receptor agonist (ACS-Fall 2023) - "Recently, Pfizer disclosed the structure of PF-067081532, an orally bioavailable, once daily, small molecule, GLP-1R agonist that is currently undergoing clinical trials. This presentation will discuss the synthetic challenges for accessing PF-07081532 and the novel dioxolane functional group comprised within it."

Diabetes • Genetic Disorders • Metabolic Disorders • Obesity

A Study to Evaluate the Effect of the Experimental GLP-1 Drug PF-07081532 on Blood Levels of Common Birth Control Pills, and Drugs Omeprazole and Midazolam, and Effect of GLP-1 Drug Semaglutide on Midazolam Blood Levels in Healthy Adults With Weight in the Obesity Range (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | Trial primary completion date: Aug 2023 ➔ Nov 2023

Enrollment closed • Trial primary completion date • Genetic Disorders • Long-acting Reversible Contraceptives • Obesity

Trial to Learn About the Study Medicine (PF-07081532) and Rybelsus in People With Type 2 Diabetes and Separately PF-07081532 in People With Obesity (clinicaltrials.gov) - P2 | N=900 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study to Understand How the Study Medicine (PF-07081532) is Processed in People With Liver Dysfunction (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Liver Failure

A Drug-Drug Interaction Study to Estimate the Effect of PF-07081532 on the Pharmacokinetics of Dabigatran and Rosuvastatin in Overweight or Obese Adult Participants (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Obesity

A Drug-Drug Interaction Study to Estimate the Effect of PF-07081532 on the Pharmacokinetics of Dabigatran and Rosuvastatin in Overweight or Obese Adult Participants (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Pfizer

New P1 trial • Obesity

A Study to Understand How the Study Medicine (PF-07081532) is Processed and Eliminated in Healthy Men (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion

A Study to Compare Two Different Forms of PF-07081532 in Adults Who Are Overweight or Obese (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

A Study to Understand How the Study Medicine (PF-07081532) is Processed in People With Liver Dysfunction (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2023 ➔ Apr 2023 | Trial primary completion date: Oct 2023 ➔ Apr 2023

Enrollment closed • Trial completion date • Trial primary completion date • Hepatology • Liver Failure

Trial to Learn About the Study Medicine (PF-07081532) and Rybelsus in People With Type 2 Diabetes and Separately PF-07081532 in People With Obesity (clinicaltrials.gov) - P2 | N=780 | Recruiting | Sponsor: Pfizer | Active, not recruiting ➔ Recruiting | N=337 ➔ 780

Enrollment change • Enrollment open • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus