GDC-0134 / Roche - LARVOL DELTA

Pinpointing novel targets for osteoarthritis: A comprehensive cross-omics integration analysis. (PubMed, Medicine (Baltimore)) - "Molecular docking results showed that GDC-0134 could effectively target DLK1, which provided a new target for targeted therapy of DLK1...USP8 and DLK1 were highlighted as promising therapeutic targets. These results offer promising avenues for creating novel therapies aimed at modifying OA progression."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • USP8

A Phase 1 study of GDC-0134, a dual leucine zipper kinase inhibitor, in ALS. (PubMed, Ann Clin Transl Neurol) - "This trial characterized GDC-0134 safety and PK, but no adequately tolerated dose was identified. NFL elevations in GDC-0134-treated patients and DLK cKO mice raised questions about interpretation of biomarkers affected by both disease and on-target drug effects. The safety profile of GDC-0134 was considered unacceptable and led to discontinuation of further drug development for ALS. Further work is necessary to understand relationships between neuroprotective and potentially therapeutic effects of DLK knockout/inhibition and NFL changes in patients with ALS."

Journal • P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Hematological Disorders • Optic Neuritis • Pain • Thrombocytopenia • MAPK8 • Plasma NfL

"my transcript of GDC-0134 #ACSSpring2021" (@egonwillighagen)

"Question: does GDC-0134 reverse disease or merely slow progression? Answer: We see slowing of disease #ACSSpring2021" (@cenmag)

"GDC-0134 #ACSSpring2021" (@cenmag)

[VIRTUAL] Discovery of GDC-0134: A potent, selective, and brain-penetrant dual leucine zipper kinase Inhibitor (ACS-Sp 2021) - "In this presentation, we will highlight our approach to balancing the property space of kinase inhibitors for the CNS. Starting from a high-throughput screening hit, we used structure-based drug design combined with a focus on CNS drug-like properties to identify GDC-0134, which advanced to clinical evaluation as a potential treatment of amyotrophic lateral sclerosis (ALS)."

Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders

"Discontinuations: RG7861 (anti S aureus ADC?) partnered with $SGEN. RG6000 = dual leucine zipper kinase inhibitor for ALS. $RHHBY" (@JacobPlieth)

A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1; N=54; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Aug 2020 ➔ Mar 2020; Trial primary completion date: Aug 2020 ➔ Mar 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders • Pain

A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1; N=54; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting ➔ Active, not recruiting; N=82 ➔ 54

Clinical • Enrollment change • Enrollment closed

A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1; N=82; Recruiting; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Recruiting; Trial completion date: Oct 2019 ➔ Aug 2020; Trial primary completion date: Oct 2019 ➔ Aug 2020

Clinical • Enrollment open • Trial completion date • Trial primary completion date

A Study to Determine the Bioavailability of Various Formulations of GDC-0134 in Healthy Female Participants of Non-Childbearing Potential (clinicaltrials.gov) - P1; N=49; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1; N=82; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study to Determine the Bioavailability of Various Formulations of GDC-0134 in Healthy Female Participants of Non-Childbearing Potential (clinicaltrials.gov) - P1; N=44; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study to Determine the Bioavailability of Various Formulations of GDC-0134 in Healthy Female Participants of Non-Childbearing Potential (clinicaltrials.gov) - P1; N=44; Recruiting; Sponsor: Genentech, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open