GDC-0214 / Roche - LARVOL DELTA

GDC-0214 Is a Potent Inhaled JAK Inhibitor With Efficacy in Multiple Pre-clinical Models of Th2 Inflammation: A Perspective on Use of In Vivo Rodent Models for Early Phase Drug Discovery (ATS 2024) - "These results highlight how, despite the inevitable difficulty and challenges of drug candidate screening in in vivo rodent models of lung inflammation, multiple avenues may lead to successful prosecution of drug discovery programs, and progression of valuable compounds to clinical development. Robust activity of GDC-0214 in these models supported progression of this compound to the clinic, and translated to successful proof of activity in humans."

Late-breaking abstract • Preclinical • Asthma • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL13 • JAK1 • STAT6

Inhaled JAK Inhibitor GDC-0214 Nanoaggregate Powder Exhibits Improved Pharmacokinetic Profile in Rats Compared to the Micronized Form: Benefits of Thin Film Freezing. (PubMed, Mol Pharm) - "In the rat PK study, formulation F20, which contains 80% GDC-0214 and 20% lactose, resulted in the highest AUC in the lungs with the lowest AUC in the plasma that corresponds to a 4.8-fold higher ratio of the lung-to-plasma exposures compared to micronized crystalline GDC-0214 powder administered by dry powder inhalation. Therefore, GDC-0214 nanoaggregates produced by TFF provided an improved dry powder for inhalation that can lead to enhanced therapeutic efficacy with a lower risk of systemic toxicity."

Journal • PK/PD data • Preclinical • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • IL5

Effects of inhaled JAK inhibitor GDC-4379 on exhaled nitric oxide and peripheral biomarkers of inflammation. (PubMed, Pulm Pharmacol Ther) - "In patients with mild asthma, 14-day treatment with GDC-4379 reduced FeNO levels and peripheral biomarkers of inflammation. Treatment was well tolerated without any major safety concerns."

Biomarker • Journal • Asthma • Immunology • Inflammation • Pain • Pulmonary Disease • Respiratory Diseases

Phase 1 and Scintigraphy Studies to Evaluate Safety, Tolerability, Pharmacokinetics, and Lung Deposition of Inhaled GDC-0214 in Healthy Volunteers. (PubMed, Clin Transl Sci) - "Tc-radiolabeled GDC-0214 (1 mg) exhibited a mean plasma Cmax similar to that observed in phase 1 at the same dose level. Overall, inhaled GDC-0214 exhibited pharmacokinetic properties favorable for inhaled administration."

Journal • P1 data • PK/PD data • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

[VIRTUAL] Inhaled JAK inhibitor GDC-4379 reduces FeNO in patients with mild asthma (ERS 2021) - "GDC-0214, an inhaled small molecule JAK1 inhibitor, has reduced FeNO ~40% in patients with mild asthma. Conclusions In patients with mild asthma, 14-day treatment with GDC-4379 reduced FeNO. Treatment was well tolerated, without evidence of systemic toxicity."

Clinical • Asthma • Immunology • Otorhinolaryngology • Pain • Pulmonary Disease • Respiratory Diseases

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

Inhaled JAK inhibitor GDC-0214 reduces exhaled nitric oxide in patients with mild asthma: a randomized, controlled, proof-of-activity trial. (PubMed, J Allergy Clin Immunol) - "GDC-0214, an inhaled JAK inhibitor, caused dose-dependent reductions in FeNO in mild asthma and was well tolerated without evidence of systemic toxicity."

Clinical • Journal • Asthma • Immunology • Inflammation • Respiratory Diseases • IL13 • IL4 • JAK1

[VIRTUAL] Inhaled JAK Inhibitor GDC-0214 Reduces Exhaled Nitric Oxide in Patients with Mild Asthma (ATS-I 2020) - "Treatment with inhaled JAK inhibitor, GDC-0214, for 10 days resulted in a dose-dependent reduction in FeNO in patients with mild asthma, and was found to be well tolerated, without evidence of systemic toxicity."

Clinical • Asthma • Infectious Disease • Respiratory Diseases • IL13 • IL4

Inhaled JAK Inhibitor GDC-0214 Reduces Exhaled Nitric Oxide in Patients with Mild Asthma (ATS 2020) - "Treatment with inhaled JAK inhibitor, GDC-0214, for 10 days resulted in a dose-dependent reduction in FeNO in patients with mild asthma, and was found to be well tolerated, without evidence of systemic toxicity."

Clinical • Asthma • Immunology • Infectious Disease • Respiratory Diseases • IL13 • IL4

A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Inhaled GDC-0214, a JAK1 Inhibitor, as Single- and Multiple-Ascending Doses in Healthy Volunteers (AAAAI 2020) - "Inhaled GDC-0214 was well tolerated in healthy volunteers with pharmacokinetics indicating low systemic exposure and long retention in the lung."

Clinical • P1 data • PK/PD data • IL13 • IL4