Blade Therapeutics Announces FDA Orphan Drug Designation Granted to Cudetaxestat for Treatment of Systemic Sclerosis
Read the full article: Blade Therapeutics
14 October 2021
- Second orphan drug designation granted by U.S. Food and Drug Administration (FDA) for cudetaxestat
- Blade plans to initiate phase 2 clinical study of cudetaxestat in idiopathic pulmonary fibrosis (IPF) in 1H-2022
SOUTH SAN FRANCISCO, Calif., October 14, 2021 – Blade Therapeutics, Inc. (Blade or the company), a biopharmaceutical company focused on developing cutting-edge treatments for debilitating fibrotic and neurodegenerative diseases, today announced that the FDA has granted orphan drug designation for cudetaxestat for the potential treatment of systemic sclerosis (SSc). Cudetaxestat is an investigational non-competitive autotaxin inhibitor in clinical development for IPF.
“There are limited options and high medical need for patients suffering from systemic sclerosis,” said Daven Mody, PharmD, MBA, vice president of regulatory affairs with Blade. “We look forward to continuing our clinical development efforts for cudetaxestat in lung fibrosis and potentially exploring other areas of high medical need such as SSc.”SSc is a chronic, progressive autoimmune disorder characterized by degenerative changes and thickening of the skin, joints, lungs, other internal organs and vascular dysfunction. The condition may be limited or diffuse. Approximately 100,000 people in the U.S. have SSc. The FDA’s Orphan Drug Designation program provides orphan status to drugs and biologics that are defined as those intended for the treatment, prevention or diagnosis of a rare disease or condition, which is one that affects less than 200,000 people in the U.S. or meets cost-recovery provisions of the act.Cudetaxestat received its first orphan drug designation in February 2021 for the potential treatment of IPF. Blade plans to initiate a phase 1 clinical study to assess the effect of cudetaxestat on the pharmacokinetics of two approved drugs for IPF (pirfenidone and nintedanib) in healthy volunteers (NCT04939467). This study is projected to start in the fourth quarter of 2021 and complete in the first quarter of 2022. Study results will be used to inform the design of a planned phase 2 clinical trial to evaluate the efficacy and safety of cudetaxestat in patients with IPF, which is anticipated to start in the first half of 2022.
Cudetaxestat (BLD-0409), a non-competitive, reversible inhibitor of autotaxin, has demonstrated direct anti-fibrotic activity and differentiating preclinical and biochemical characteristics which support the potential for a treatment profile in lung and liver fibrosis. Available data from completed phase 1 studies have shown that cudetaxestat was well tolerated with a demonstrated pharmacokinetic/pharmacodynamic correlation and biomarker activity, and a supportive clinical safety profile. Cudetaxestat has been granted orphan drug designations in the treatment of IPF and SSc. Cudetaxestat is an investigational medicine that is not approved for commercial use by the FDA or any other regulatory authority.
Pro-fibrotic processes are stimulated by autotaxin, a key enzyme responsible for generating the potent signaling lipid lysophosphatidic acid (LPA). Excessive autotaxin levels and activity play a central role in various fibrotic diseases and occur in response to epithelial cell/tissue damage, leading to elevated levels of LPA. LPA binds to LPA receptors on myofibroblasts, thereby triggering a signaling cascade that leads to myofibroblast activation/differentiation. Activated myofibroblasts produce extracellular matrix proteins that make up the fibrotic lesion (organ/tissue scarring). Increased autotaxin levels and activity are associated with liver, lung, kidney, and skin fibrosis. In addition, autotaxin levels correlate with fibrosis severity in various liver diseases (e.g., nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH)). Inhibition of the autotaxin pathway has been clinically validated in IPF.
Fibrosis is a complex, pathologic process involving the development of organ/tissue scarring characterized by deposition of extracellular matrix proteins that develop in response to aberrant cell/tissue damage. Excessive fibrosis disrupts normal architecture and function of organs/tissues. Later-stage fibrotic disease is marked by poor outcomes and high morbidity and mortality. Diseases characterized by uncontrolled, progressive fibrosis include IPF, SSc, and NASH. New well-tolerated therapies that provide robust attenuation of disease progression are needed to address the high burden of fibrotic and neurodegenerative diseases.
Blade Therapeutics, Inc. is a biopharmaceutical company focused on developing cutting-edge treatments for debilitating, incurable fibrotic and neurodegenerative diseases that impact millions of people worldwide. The company has deep expertise in novel biological pathways – including autotaxin / LPA and calpain biology – that are foundational to cell- and tissue-damage responses resulting from protein deposition or aggregation associated with fibrotic and neurodegenerative diseases. Blade expects to advance a differentiated pipeline of oral, small-molecule therapies that include a non-competitive autotaxin inhibitor and inhibitors of dimeric calpains designed for potential treatment of lung, liver and cardiac fibrosis or neurodegenerative diseases. The company’s focused approach offers the potential to produce disease-modifying, life-saving therapies. Visit www.blademed.com for more information and follow Blade on LinkedIn.