Revolutionizing AATD Treatment: Emerging Therapies to Replace Augmentation Therapy

Current Treatment Limitations:

The only approved treatment for AATD is augmentation therapy, which involves weekly intravenous administration of normal alpha-1 antitrypsin collected from blood donors. However, this treatment does not reverse pulmonary damage or stop the progression of liver damage.

Emerging Therapies:

Companies like Arrowhead Pharmaceuticals and Takeda are developing RNA interference (RNAi) therapies, such as fazirsiran, which aim to reduce the production of abnormal alpha-1 antitrypsin (Z-AAT) in the liver.
Intellia Therapeutics is working on NTLA-3001, a CRISPR-based gene editing treatment designed to insert a healthy copy of the SERPINA1 gene to restore normal alpha-1 antitrypsin production.
Sanofi is developing SAR447537 (formerly INBRX-101), a fusion protein that could potentially be administered every three or four weeks, offering a more convenient alternative to current weekly infusions.

Potential Impact:

These new therapies could transform the treatment of AATD by addressing the underlying damage and potentially making augmentation therapy obsolete within the next 5 to 10 years.
Successful development of these therapies could lead to improved patient outcomes, including reduced need for frequent infusions and potential prevention of lung and liver disease progression.

Challenges and Setbacks:

Some companies, like Vertex Pharmaceuticals, have faced setbacks in their AATD research, highlighting the challenges in developing effective treatments for this genetic disorder.
Previous attempts at RNAi therapy have shown promise but also encountered issues such as liver enzyme elevation, necessitating further development and refinement.

Future Prospects:

The development of these new therapies is ongoing, with several candidates in various stages of clinical trials. Positive outcomes could lead to these treatments becoming available within the next few years.