āshibio, a clinical-stage biotechnology company, has announced the dosing of the first patient in the ANDECAL study, a Phase 2/3 clinical trial evaluating andecaliximab for the treatment of fibrodysplasia ossificans progressiva (FOP). This milestone marks a significant step in the development of a potential new therapy for this rare and debilitating genetic disorder.
Targeting Heterotopic Ossification in FOP
Fibrodysplasia ossificans progressiva (FOP) is characterized by progressive heterotopic ossification (HO), a condition where bone forms in muscles, tendons, and ligaments. This leads to severe disability and a shortened lifespan. Currently, treatment options for FOP are limited, highlighting a significant unmet medical need.
"Heterotopic ossification, or HO, is a devastating condition with significant unmet need. We are initiating development in fibrodysplasia ossificans progressiva, a rare genetic disease characterized by severe and progressive HO leading to profound disability and shortened life span," said āshibio Chief Executive Officer Pankaj Bhargava, MD.
Andecaliximab: A Novel MMP-9 Inhibitor
Andecaliximab is a humanized antibody that specifically inhibits matrix metalloproteinase-9 (MMP-9). Researchers have identified MMP-9 as a potential therapeutic target for FOP. A study published in the Journal of Bone and Mineral Research (JBMR) in February 2024 highlighted a unique patient with the classic FOP mutation but minimal symptoms, who also carries mutations in the MMP-9 gene. This suggests that blocking MMP-9 could protect against heterotopic ossification. Further experiments in mouse models of FOP confirmed that targeting MMP-9 led to a substantial reduction in HO.
"This unique person revealed something that could significantly change the lives of people with FOP," said Frederick S. Kaplan, MD, one of the study’s senior authors and the Isaac and Rose Nassau Professor of Orthopaedic Molecular Medicine at the University of Pennsylvania. "We hope that ongoing efforts will validate what we found and provide a path toward quality treatment for individuals with FOP."
ANDECAL Trial Design
The ANDECAL study is a Phase 2/3 trial consisting of two parts. Part 1, currently underway in the United States, is a randomized study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of two different doses of andecaliximab. It also includes a preliminary efficacy assessment in individuals with FOP. Part 1 consists of two cohorts: Cohort 1a includes individuals aged 15 years and older who will undergo a NaF PET scan, while Cohort 1b includes individuals aged 12 years and older experiencing flare-ups. Following Part 1, āshibio plans to initiate Part 2, a double-blind, placebo-controlled registration study, at sites in the U.S. and selected countries globally.
Edward Hsiao, MD, PhD, Professor in the Division of Endocrinology and Metabolism and Director of the Metabolic Bone Clinic at the University of California, San Francisco, enrolled the first participant dosed in the ANDECAL study. "We are excited to initiate enrollment in the ANDECAL trial. I am grateful to the UCSF team and my colleague Dr. Kelly Wentworth for all their efforts in making this study available to our patients with FOP," said Dr. Hsiao.
Regulatory Status
The U.S. Food and Drug Administration (FDA) has granted andecaliximab a Rare Pediatric Disease Designation (RPDD) for the treatment of FOP. This designation is given to potential treatments for serious or life-threatening rare diseases affecting fewer than 200,000 people in the U.S., primarily under the age of 18.
"The advancement of andecaliximab into the clinic is a significant milestone in our mission to improve the lives of those living with FOP and other forms of HO," said āshibio Chief Medical Officer, Deborah Wenkert, MD. "We are deeply grateful to the participants for taking part in this important study, and to the investigators for their partnership in helping to advance this potential treatment to address the unmet needs of individuals living with FOP."
