Critical Path for Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency affects more than 3 million people globally; there is no cure. With wide variability in patient experience due in part to genetic and diagnostic differentials, the challenges for clinicians, drug developers, patients, caregivers and regulators are great.

• AATD is an under-recognized rare disease. Patients are geographically scattered, exhibit varied phenotypes, and experience unpredictable disease progression. New mutations are continually discovered.
• Clinical management typically includes augmentation therapy to increase AAT pulmonary levels to slow further damage. Augmentation therapy cannot reverse existing damage or restore lost lung function, and weekly infusions for pulmonary symptoms present both logistical and financial challenges for patients, especially as a lifelong commitment.
• Currently, there are no treatments outside of organ transplant that target extrapulmonary symptoms, particularly liver disease.
• The limited population and the costly nature of clinical studies render the development of new treatments less enticing for drug developers; the last therapy was approved over 25 years ago.
• Conventional lung disease biomarkers don’t effectively measure AATD, complicating the task of gathering substantial evidence for efficacy within a small patient group.
• While gene and RNA therapies hold promise for innovative treatments, precision medicine, and hope towards a cure for AATD patients, significant gaps exist between scientific advancements and regulatory standards required to ensure these therapies are safely and appropriately evaluated in humans.

The CPA-1 consortium’s mission is to forge actionable, regulatory-endorsed drug development solutions for patients living with alpha-1 antitrypsin deficiency by convening key stakeholders in a public-private partnership dedicated to open collaboration. CPA-1 consortium members bring data, individual and organizational expertise, and a desire for change to hepatic and pulmonary workgroup sessions. Data and research sharing ensure drug development solutions reflect current scientific knowledge and regulatory standards.

Alpha-1 antitrypsin deficiency is an inherited condition that is frequently under- or mis-diagnosed until lung or liver disease sets in. AATD patients face daily challenges in breathing, maintaining health, and socioeconomic status. By bringing the best minds to the table and assessing the landscape from patient, academic, and industry vantage points, the CPA-1 consortium has the potential to directly address this public health burden through innovations in biomarkers, therapeutic modalities, and trial design.

The consortium’s success will be measured by work that:

• Grows an AATD-specific database to harness aggregated data from clinical trials, longitudinal observational research, and registries to support regulatory submission of novel drug development tools.
• Elevates to regulators the patient and caregiver perspective on the true burden of disease, desire for therapeutic benefits, tolerance of unknowns and risks for innovative therapies, and willingness to participate in clinical trials.
• Facilitates participation in and evaluation of innovative clinical trials, accelerating new treatment modalities that hold promise to reduce the societal burden of disease.
• Disseminates workgroup initiatives and knowledge through web-based and open access publications and presentations for shared learning.

To learn more or contribute to the CPA-1 database on the RDCA-DAP, email: cpa1@c-path.org 

• Beam Therapeutics
• CSL Behring
• Sanofi
• Takeda

• Alpha-1 Foundation
• Alpha1 MZ Foundation
• Community Liver Alliance
• COPD Foundation
• Global Liver Institute
• Open Source Imaging Consortium (OSIC)