Alpha-1 Antitrypsin Deficiency
Alpha-1 Antitrypsin Deficiency (AATD) is a rare disease caused by low levels of the Alpha-1 Antitrysin protein. It can lead to lung disease and liver disease. Liver disease in particular effects 15% of adults living with AATD and 10% of infants living with the condition. Symptoms of liver disease in AATD are dark urine, chronic itching, cirrhosis, elevated liver enzymes, jaundice, and a swollen abdomen. Patients with AATD associated liver disease have an increased risk of developing liver cancer. This condition unfortunately has limited treatment options.
But Arrowhead Pharmaceuticals has just announced that they plan to initiate a Phase 2/3 clinical trial for liver disease in alpha-1 antitrypsin deficiency (AATD) in the second quarter of this year. The company believes that this trial could serve as a registrational study of the therapy, called ARO-AAT. The Investigational New Drug application (IND) for the Phase 2/3 trial of this therapy has officially been submitted to the FDA.
ARO-AAT is Arrowhead’s second generation RNAi therapeutic which is administered subcutaneously. AATD associated liver disease is severely lacking in treatment options, and Arrowhead hopes that this therapy could bring a new therapeutic option to patients.
Phase 2/3 Trial
The proposed primary endpoints of this Phase 2/3 trial are safety, efficacy, and pharmacodynamic dose response. Efficacy will be measured by any improvement in the histologic grading scale of liver disease in AATD. Additionally, liver fibrosis will be examined using the Ishak score.
Arrowhead hopes to initiate this trial at multiple sites in the United States. Following initiation of the trial at these locations, they plan to bring the trial to various sites in Europe.
Of course, this trial is pending regulatory review of the company’s IND but Arrowhead is extremely hopeful about ARO-AAT’s potential. They say that their communications with the FDA thus far have been helpful and productive and they are excited about moving forward in their investigation of this treatment.
Hopefully, this Phase 2/3 study will culminate in a new therapeutic option for patients living with alpha-1 liver disease.
You can read more about this IND and ARO-AAT’s potential here.
