Horizon Therapeutics plc Announces First Patient Enrolled in Phase 2b Pivotal Trial Evaluating HZN-825 for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)

Horizon Therapeutics plc (Nasdaq: HZNP) today announced the first patient has enrolled in a Phase 2b pivotal trial to evaluate its development-stage medicine HZN-825, a lysophosphatidic acid receptor 1 (LPAR₁) antagonist to treat people with IPF, the most common interstitial lung disease.

IPF is a rare, progressive lung disease caused by inflammation and fibrosis, or scarring, of the lungs. It is characterized by dyspnea, chronic cough and potentially death. There are approximately 100,000¹ people who live with IPF in the United States, and the disease has a median survival of less than five years.

“Patients with idiopathic pulmonary fibrosis know their condition will only worsen over time and deserve therapies that will stabilize or slow the progression of this disease,” said Martin Kolb, M.D., Ph.D., division director, Respirology, McMaster University and primary investigator for the trial. “This trial will help determine the safety, efficacy and tolerability of Horizon’s LPAR₁ antagonist in slowing the decline of lung function due to inflammation and fibrosis from this disease.”

Approximately 360 subjects who meet the trial eligibility criteria will be randomized in a 1:1:1 ratio to receive HZN-825 at 300 mg once daily, HZN-825 at 300 mg twice daily or placebo for 52 weeks. The primary endpoint is change in forced vital capacity (FVC) after 52 weeks. This is an objective endpoint that measures lung capacity and is used to assess the progression of lung disease and the effectiveness of the treatment.

Secondary endpoints include the 6-Minute Walk Test (6MWT), the King’s Brief Interstitial Lung Disease (K-BILD) Questionnaire, rate of hospitalization due to respiratory distress, and a composite endpoint of progression-free survival. Enrollment is expected to take approximately two years.

“Preclinical studies have demonstrated that targeting LPAR₁ has the potential to prevent and possibly reverse the underlying pathologies characteristic of idiopathic pulmonary fibrosis,” said Theresa Podrebarac, M.D., M.Sc., senior vice president, clinical development, Horizon. “The enrollment of the first patient in this pivotal study marks an important milestone for development of this potential therapy for these patients and our commitment to fibrotic conditions.”

Results of HZN-825 Phase 2a Study in Patients with Early Diffuse Cutaneous Systemic Sclerosis

The Phase 2b pivotal trial initiation follows encouraging efficacy and safety data in a Phase 2a trial in patients with early diffuse cutaneous systemic sclerosis.² The placebo-controlled 8-week trial of HZN-825 in diffuse cutaneous systemic sclerosis, completed in 2018, showed a positive trend in response, with an improvement in the modified Rodnan skin thickness score, or mRSS, which is a secondary endpoint in the Phase 2b pivotal trial.

Additionally, data from the 16-week open-label extension period of the Phase 2a trial suggests that longer treatment duration may show more meaningful benefit. Seventy-nine percent of patients who received 24 weeks of treatment responded with a clinically meaningful improvement in mRSS.²

About HZN-825

HZN-825 is an oral selective LPAR₁ antagonist that has shown early signs of clinical impact in systemic sclerosis. LPAR₁ signaling has been implicated in fibrosis and inflammation, and preclinical and clinical evidence support the antifibrotic potential of LPAR₁ antagonism across multiple organ systems, including both lung and skin.

About Horizon

Horizon is focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

Forward-Looking Statements

This press release contains forward-looking statements, including, but not limited to, statements related to the potential benefits of HZN-825; the expected scope, endpoints and timing of Horizon’s Phase 2b pivotal trial of HZN-825 and other statements that are not historical facts. These forward-looking statements are based on Horizon’s current expectations and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to clinical trials, including the fact that prior results may not predict future clinical trial outcomes; impacts of the COVID-19 pandemic and actions taken to slow its spread, including potential delays in clinical trials; regulatory obligations and oversight, including any changes in the legal and regulatory environment in which Horizon operates and those risks detailed from time-to-time under the caption “Risk Factors” and elsewhere in Horizon’s filings and reports with the SEC. Horizon undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information.

References

1. Barratt SL, Creamer A, Hayton C, Chaudhuri N. Idiopathic pulmonary fibrosis (IPF): an overview. J Clin Med. 2018;7(8):201.
2. Allanore Y, Distler O, Jagerschmidt A, et al. Lysophosphatidic acid receptor 1 antagonist SAR100842 for patients with diffuse cutaneous systemic sclerosis: a double-blind, randomized, eight-week placebo-controlled study followed by a sixteen-week open-label extension study. Arthritis Rheumatol. 2018;70(10):1634-1643.

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