fipaxalparant (AMG 670) / Amgen - LARVOL DELTA

A pharmacokinetics study to evaluate drug-drug interactions between fipaxalparant and concomitant medications in healthy participants. (PubMed, Clin Pharmacol Drug Dev) - "This phase 1, open-label, crossover, 3-cohort study in healthy adults evaluated mutual drug-drug interactions (DDIs) between fipaxalparant and the IPF medications pirfenidone and nintedanib, as well as the effects of itraconazole (P-glycoprotein inhibitor) and rifampin (potent organic anion transporting polypeptide [OATP] inhibitor) on fipaxalparant. Overall, fipaxalparant absorption in vivo occurs independently of the P-glycoprotein-mediated gut efflux pathway, and fipaxalparant is a clinically relevant OATP substrate. Results of this DDI study will inform the management of concomitant medications of ongoing/future trials of fipaxalparant."

Journal • PK/PD data • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Development and optimization of a commercial manufacturing process for key fipaxalparant drug substance intermediate aminoindane (ACS-Fall 2025) - "Amgen evaluated fipaxalparant in phase 2 studies that enrolled patients with skin fibrosis (diffuse cutaneous systemic sclerosis (dcSSc)) and idiopathic pulmonary fibrosis (IPF), a chronic disease that causes the lungs to scar and makes it more difficult to breathe.The proposed regulatory commercial manufacturing route of fipaxalparant presented in this publication revolves around the recent development of a new, rapid and highly effective one-pot, two-step manufacturing process to produce a unique key bicyclic drug substance intermediate "aminoindane".This presentation will focus on the chemical development of the new aminoindane process (route scouting and process development via Design of Experiments), and the first GLP kilo scale-up, demonstrating that the new process is able to quickly supply material with good yields and excellent purity. A proof of concept "use test" and initial demonstration batch at pilot scale, performed at the fipaxalparant..."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

An Open-label Extension Trial of HZNP-HZN-825-301 in Adult Participants With Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc) (clinicaltrials.gov) - P2 | N=174 | Terminated | Sponsor: Amgen | Enrolling by invitation ➔ Terminated; Decision to terminate is due to the parent trial (HZNP-HZN-825-301) meeting pre-defined criteria for futility

Trial termination • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=301 | Terminated | Sponsor: Amgen | Phase classification: P2/3 ➔ P2 | Trial completion date: Sep 2025 ➔ Feb 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2025 ➔ Feb 2025; The study was terminated due to meeting pre-defined criteria for futility.

Phase classification • Trial completion date • Trial primary completion date • Trial termination • Immunology • Scleroderma • Systemic Sclerosis

AMGEN REPORTS FOURTH QUARTER AND FULL YEAR 2024 FINANCIAL RESULTS (PRNewswire) - "A Phase 2 study of fipaxalparant in patients with diffuse cutaneous systemic sclerosis is complete. The study did not meet the primary or secondary endpoints. Further development of fipaxalparant in this indication will be discontinued....TEZSPIRE: The Company is planning to initiate Phase 3 studies in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and a BEC ≥ 150 cells/µl. Study initiation is anticipated in H1 2025....Regulatory submission is anticipated in H1 2025....In severe asthma, the WAYFINDER Phase 3b study is complete...The SUNRISE Phase 3 study will be discontinued due to limited enrollment."

Discontinued • Filing • New P3 trial • Trial completion • Trial termination • Asthma • Chronic Obstructive Pulmonary Disease • Systemic Sclerosis

An Open-label Extension Trial of HZNP-HZN-825-301 in Adult Participants With Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc) (clinicaltrials.gov) - P2 | N=240 | Enrolling by invitation | Sponsor: Amgen | Trial completion date: Sep 2026 ➔ Feb 2025 | Trial primary completion date: Sep 2026 ➔ Feb 2025

Trial completion date • Trial primary completion date • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=153 | Terminated | Sponsor: Amgen | Trial completion date: Jul 2025 ➔ Jan 2025 | Active, not recruiting ➔ Terminated; The trial was terminated due to not meeting primary or key secondary endpoints.

Trial completion date • Trial termination • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Amgen ghosts lung disease program after missing all 14 endpoints (FierceBiotech) - P2b | N=153 | NCT05032066 | Sponsor: Amgen | "Amgen is discontinuing a lung disease program after its investigational small molecule failed to hit any of the primary or secondary endpoints in a midstage study...Amgen tested fipaxalparant in a phase 2 study that enrolled 153 patients with idiopathic pulmonary fibrosis, a chronic disease that causes the lungs to scar and makes it more difficult to breathe...The trial failed to hit its primary goal, which measured the percent change in maximum amount of air patients could forcefully exhale after 52 weeks of treatment. The study also included 13 secondary outcomes...all of which failed to meet their goals....With the disappointing results in hand, Amgen has decided to discontinue the asset in the lung indication. The termination includes an open-label extension of the lung trial."

P2b data • Pipeline update • Trial termination • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=301 | Active, not recruiting | Sponsor: Amgen | Trial primary completion date: Oct 2024 ➔ Sep 2025

Trial primary completion date • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=301 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Scleroderma • Systemic Sclerosis

Fipaxalparant: Data from P2 trial (NCT05032066) for IPF in H2 2024 (Amgen) - Q2 2024 Results

P2 data • Idiopathic Pulmonary Fibrosis

Pharmacokinetics of Fipaxalparant, a Small-Molecule Selective Negative Allosteric Modulator of Lysophosphatidic Acid Receptor 1, and the Effect of Food in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "At 450 mg, a high-fat meal increased the maximum observed concentration and area under the curve by approximately 1.9- and 2.1-fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies."

Journal • PK/PD data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Amgen | Trial primary completion date: Jul 2025 ➔ Aug 2024

Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

An Open-label Extension Trial of HZNP-HZN-825-301 in Adult Participants With Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc) (clinicaltrials.gov) - P2 | N=246 | Enrolling by invitation | Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland | Trial completion date: Dec 2025 ➔ Jul 2026 | Trial primary completion date: Dec 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

Fipaxalparant: Data from P2 trial (NCT05032066) for IPF in H2 2024 (Amgen) - Q4 2023 Results

P2 data • Idiopathic Pulmonary Fibrosis

A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=153 | Active, not recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Phase classification: P2b ➔ P2

Phase classification • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

PHARMACOKINECTS STUDY TO EVALUATE DRUG-DRUG INTERACTIONS (DDI) BETWEEN HZN-825 AND PIRFENIDONE/NINTEDANIB (CHEST 2023) - "The study demonstrated no relevant mutual DDI between HZN-825 and pirfenidone/nintedanib at clinical doses. CLINICAL IMPLICATIONS: These data support allowing pirfenidone and nintedanib as concomitant medications with HZN-825 in ongoing/future clinical trials."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

An Open-label Extension Trial of HZNP-HZN-825-301 in Adult Participants With Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc) (clinicaltrials.gov) - P2 | N=246 | Enrolling by invitation | Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland | Recruiting ➔ Enrolling by invitation

Enrollment status • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Trial completion date: Dec 2024 ➔ Jul 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2b | N=153 | Active, not recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

An Open-label Extension Trial of HZNP-HZN-825-301 in Adult Participants With Diffuse Cutaneous Systemic Sclerosis (Diffuse Cutaneous SSc) (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland

New P2 trial • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Trial completion date: Jul 2023 ➔ Dec 2024 | Trial primary completion date: Jul 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2b | N=135 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | N=360 ➔ 135 | Trial completion date: Oct 2023 ➔ Jul 2025 | Trial primary completion date: Sep 2023 ➔ Jun 2024

Enrollment change • Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Open-label Study to Evaluate the Efficacy, Safety, Tolerability of HZN-825 in Patients with Diffuse Cutaneous Systemic Sclerosis (clinicaltrialsregister.eu) - P2 | N=240 | Ongoing | Sponsor: Horizon Therapeutics Ireland DAC

New P2 trial • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2; N=300; Recruiting; Sponsor: Horizon Therapeutics Ireland DAC; Not yet recruiting ➔ Recruiting; Phase classification: P2/3 ➔ P2

Enrollment open • Phase classification • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis • CRP