efmarodocokin alfa (RG7880) / Roche - LARVOL DELTA

An update on IL-22 therapies in alcohol-associated liver disease and beyond. (PubMed, Am J Pathol) - "Studies from preclinical models and early-phase clinical trials of IL-22 agonists, such as F-652 and UTTR1147A, have shown favorable safety profiles, good tolerability, and encouraging efficacy in reducing liver injury and promoting regeneration...Further research is needed to optimize IL-22-based therapies and clarify their roles within a comprehensive approach to ALD management. This review summarizes the current understanding of IL-22 biology and its role in ALD pathophysiology and ALD-associated complications along with therapeutic application of IL-22, potential benefits and limitations."

Journal • Review • Fibrosis • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Nephrology • Oncology • Renal Disease • Solid Tumor • IL22

A randomized phase 2 study of efmarodocokin alfa, an IL-22 agonist, versus vedolizumab in patients with ulcerative colitis. (PubMed, Clin Gastroenterol Hepatol) - P2 | "Efmarodocokin alfa did not demonstrate efficacy compared to placebo and this phase 2 study was ended early for futility; however, there was evidence of target engagement (skin AEs, REG3A levels); NCT03558152."

Journal • P2 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • CRP • IL22 • REG3A

Sialic Acid Mediated Endothelial and Hepatic Uptake: a Mechanism based Mathematic Model Elucidating the Complex Pharmacokinetics and Pharmacodynamics of Efmarodocokin Alfa, a Variably Glycosylated Fusion Protein. (PubMed, J Pharm Sci) - "Our model prediction suggests an average of 1 mol/mol SA increase leads to a 50% increase in drug exposure. This underlines the significance of controlling sialic acid levels during lot-to-lot manufacturing."

Journal • PK/PD data • IL22 • MUC4

Population pharmacokinetics and pharmacodynamics of efmarodocokin alfa (IL-22Fc). (PubMed, J Pharmacokinet Pharmacodyn) - "The indirect response PD model adequately described the longitudinal changes of REG3A after efmarodocokin alfa treatment. A popPK and PD model for efmarodocokin alfa and REG3A was developed and covariates affecting the PK and PD were identified."

Journal • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • CRP • IL22 • REG3A

An Extension Study to Evaluate the Long-Term Safety and Tolerability of UTTR1147A in Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease (clinicaltrials.gov) - P2 | N=143 | Terminated | Sponsor: Genentech, Inc. | Completed ➔ Terminated; This study was terminated early by the Sponsor based on the interim analysis of Study GA39925 (NCT03558152) that showed low efficacy of UTTR1147A in ulcerative colitis. Development of the drug in this indication has been terminated.

Trial termination • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Study to Evaluate the Safety and Pharmacokinetics of Efmarodocokin Alfa in Combination With Standard of Care in Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Myelodysplastic Syndrome • Transplantation • HLA-B • HLA-C • HLA-DRB1

Roche Abandons AKT Prostate Cancer Asset (BioSpace) - "Roche is also punting its early-stage candidate efmarodocokin alfa, which was in a Phase I trial for acute graft-versus-host disease, zinpentraxin alfa, a candidate for idiopathic pulmonary fibrosis, and its Alzheimer’s hopeful, gantenerumab."

Discontinued • Acute Graft versus Host Disease • Alzheimer's Disease • Graft versus Host Disease • Idiopathic Pulmonary Fibrosis

Dose escalation randomised study of efmarodocokin alfa in healthy volunteers and patients with ulcerative colitis. (PubMed, Gut) - P1 | "Efmarodocokin alfa had an adequate safety and pharmacokinetic profile in HVs and patients. Biomarker data confirmed IL-22R pathway activation in the colonic epithelium. Results support further investigation of this non-immunosuppressive potential inflammatory bowel disease therapeutic."

Journal • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pruritus • Ulcerative Colitis • IL22

Astegolimab or Efmarodocokin Alfa in Patients With Severe COVID-19 Pneumonia: A Randomized, Phase 2 Trial. (PubMed, Crit Care Med) - "Treatment with astegolimab or efmarodocokin alfa did not improve time to recovery in patients with severe COVID-19 pneumonia."

Journal • P2 data • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL22 • IL33

An Extension Study to Evaluate the Long-Term Safety and Tolerability of UTTR1147A in Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease (clinicaltrials.gov) - P2 | N=143 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jan 2024 ➔ Jul 2022 | Trial primary completion date: Jan 2024 ➔ Jul 2022

Trial completion • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Study to Evaluate the Safety and Pharmacokinetics of Efmarodocokin Alfa in Combination With Standard of Care in Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Myelodysplastic Syndrome • Transplantation • HLA-B • HLA-C • HLA-DRB1

An Extension Study to Evaluate the Long-Term Safety and Tolerability of UTTR1147A in Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease (clinicaltrials.gov) - P2 | N=143 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting | N=320 ➔ 143 | Trial completion date: Feb 2025 ➔ Jan 2024 | Trial primary completion date: Feb 2025 ➔ Jan 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of UTTR1147A Compared With Placebo and With Vedolizumab in Participants With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2; N=195; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Dec 2022 ➔ Dec 2021; Trial primary completion date: Jul 2022 ➔ Dec 2021

Clinical • Trial completion • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Study to Evaluate the Safety and Pharmacokinetics of UTTR1147A in Combination With Standard of Care in Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Genentech, Inc.; Trial completion date: Oct 2023 ➔ Apr 2023; Trial primary completion date: Oct 2023 ➔ Apr 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Myelodysplastic Syndrome • Transplantation • HLA-DRB1

Identification of an IL-22-Dependent Gene Signature as a Pharmacodynamic Biomarker. (PubMed, Int J Mol Sci) - "The response to IL-22Fc (UTTR1147A, an Fc-stabilized version of IL-22) was assessed in HT-29 cells by microarray, and the selected responsive genes were confirmed by qPCR...An IL-22-dependent gene signature was identified that could serve as a pharmacodynamic biomarker in intestinal biopsies to support the clinical development of an IL-22 therapeutic. The differential gene expression pattern in the presence of IL-1β suggests that an inflammatory cytokine milieu in the disease setting could influence the clinical responses to IL-22."

Biomarker • Journal • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL1B • IL1R1 • IL22 • IL6

Clinical trial may have helped COVID patient beat life-threatening pneumonia (VCU Health) - "When the pandemic hit, there were no approved treatments for COVID-19. VCU Health worked quickly to join several trials and bring cutting-edge treatments to its patients. Pee-J qualified for a trial testing the safety and efficacy of two drugs, MSTT1041A and UTTR1147A, in fighting severe COVID-19 pneumonia in hospitalized patients....That trial was....Arun Sanyal, M.D."

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of UTTR1147A Compared With Placebo and With Vedolizumab in Participants With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2; N=195; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Roche culls 2 COVID-19 drug hopefuls amid Q1 clear-out (FierceBiotech) - "Roche has cut a series of experimental lung drugs from its pipeline...Astegolimab (aka RG6149), works by stopping the binding of IL-33 to ST2. This has already flopped in asthma, like so many other IL-33s, but the Swiss giant thought it could help COVID patients with pneumonia. The trial was started last year and was slated to end in January; presumably, the results were not good, as Roche said in its first-quarter results presentation (PDF) today that it has been 'removed from phase 2'....Efmarodocokin alfa (aka RG7880), which hits IL-22 and was also 'removed from phase 2'....It did, however, have better news on a different antiviral approach, with a phase 3 test of its oral COVID-19 antiviral AT-527, partnered with Atea, slated to start in the second quarter. It also cut two phase 1 asthma prospects: RG6151 and RG6244. The former is an inhaled JAK 1 inhibitor, a class beset by safety issues and commercial struggles."

Discontinued • New P3 trial • Asthma • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

An Extension Study to Evaluate the Long-Term Safety and Tolerability of UTTR1147A in Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease (clinicaltrials.gov) - P2; N=320; Recruiting; Sponsor: Genentech, Inc.; Trial completion date: Dec 2022 ➔ Feb 2025; Trial primary completion date: Dec 2022 ➔ Feb 2025

Clinical • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of UTTR1147A Compared With Placebo and With Vedolizumab in Participants With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2; N=270; Recruiting; Sponsor: Genentech, Inc.; Trial completion date: Jan 2022 ➔ Dec 2022; Trial primary completion date: Aug 2021 ➔ Jul 2022

Clinical • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

COVASTIL: A Study to Evaluate the Safety and Efficacy of MSTT1041A (Astegolimab) or UTTR1147A in Patients With Severe COVID-19 Pneumonia (clinicaltrials.gov) - P2; N=410; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Novel Coronavirus Disease • Pneumonia

COVASTIL: A Study to Evaluate the Safety and Efficacy of MSTT1041A (Astegolimab) or UTTR1147A in Patients With Severe COVID-19 Pneumonia (clinicaltrials.gov) - P2; N=410; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Pneumonia

COVID-19 clinical trials expand for hospitalized patients and outpatients - "...Dr. Raksha Jain...Principal Investigator for a rapidly expanding trial sponsored by Genentech evaluating the safety and efficacy of two investigational drugs, MSTT1041A (anti-ST2) and UTTR1147A (IL-22-Fc), for 300 patients nationwide with severe COVID-19 pneumonia. Testing is aimed at targeting the inflammatory pathways involved in COVID-19."

Novel Coronavirus Disease

COVASTIL: A Study to Evaluate the Safety and Efficacy of MSTT1041A (Astegolimab) or UTTR1147A in Patients With Severe COVID-19 Pneumonia (clinicaltrials.gov) - P2; N=390; Recruiting; Sponsor: Genentech, Inc.; N=300 ➔ 390; Trial completion date: Oct 2020 ➔ Mar 2021; Trial primary completion date: Sep 2020 ➔ Jan 2021

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Study to Evaluate the Safety and Pharmacokinetics of UTTR1147A in Combination With Standard of Care in Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Genentech, Inc.

Clinical • Combination therapy • New P1 trial • Graft versus Host Disease • Immunology • Leukemia • Myelodysplastic Syndrome • Transplantation • HLA-DRB1