NESS ZIONA, Israel—Late August saw Kamada Ltd., a plasma-derived protein therapeutics company focused on orphan indications, announce positive top-line results for the company’s Phase 2 trial in the United States of its proprietary inhaled alpha-1 antitrypsin (AAT) therapy for the treatment of alpha-1 antitrypsin deficiency (AATD).
The experimental therapeutic met its primary endpoint, the company reported, adding that the study results not only demonstrated significant increase in endothelial lining fluid inhibitory capacity, but also showed that inhaled AAT is the most efficient way of delivering therapeutic amounts of AAT to the primary sites of potential lung injury.
AATD is a rare inherited disorder, the signs and symptoms of which tend to first develop between ages 20 and 50. These symptoms mostly affect the lungs, and affected individuals often develop emphysema. But the liver is also a concern—about 15 percent of adults with AATD develop cirrhosis. In rare cases, people with AATD develop a skin condition called panniculitis. The disease is currently treated by intravenous AAT augmentation therapy.
This U.S. trial was a double-blind, placebo-controlled study evaluating the safety and efficacy of AAT by inhalation in 36 AATD patients. Patients were treated with Kamada’s AAT for inhalation (80 mg/day or 160 mg/day) or placebo via the eFlow device for 12 weeks during the double-blind period. Primary efficacy measures included antigenic AAT levels and anti-neutrophil elastase inhibitory (ANEC) levels in the lung as well as additional anti-proteolitic and anti-inflammatory biomarkers. Following this double-blind period, eligible patients (a total of 26) entered an additional 12-week open-label extension study with the active drug (160mg/day) to further assess safety and tolerability.
AATD patients treated with Kamada’s inhaled AAT demonstrated a significant increase in endothelial lining fluid (ELF) AAT antigenic level compared to the placebo group—in fact, these results showed more than twice the increase of ELF antigenic AAT level that were observed in Kamada’s previously completed pivotal study related to intravenous (IV) AAT. Antigenic AAT represents the total amount of AAT in the lung, both active and inactive.
In addition, ELF ANEC levels also increased significantly. The increase in ELF ANEC level was also more than twice that demonstrated in Kamada’s previously completed IV AAT study. The ANEC level represents the active AAT that can counterbalance further damage by neutrophil elastase.
“These measures of AAT concentration at the lung target site are extremely encouraging, demonstrating that the inhaled formulation provides substantially higher levels of antigenic AAT and ANEC than those achieved with the existing standard of care given by IV injection,” said Dr. Naveh Tov, Kamada’s vice president of clinical development and medical director for pulmonary diseases.
“The results of this study are extremely compelling,” echoed Dr. Mark Brantly, the primary investigator in this study, who serves as a vice chair of research in the Department of Medicine and chief of the Division of Pulmonary, Critical Care and Sleep Medicine at the University of Florida College of Medicine. He is also a professor of medicine, molecular genetics and microbiology at the university and an Alpha One Foundation research professor. “Based on the results of this study, it is clear that inhaled AAT is the most effective mode of treatment for reaching the primary sites of potential lung injury and restoring AAT inhibitory capacity. I look forward to the start of a pivotal study in the U.S. to confirm these results.”
Kamada’s inhaled AAT also demonstrated a strong safety profile, adding to the safety data generated in the company’s previously completed European Phase 2/3 clinical study of inhaled AAT for the treatment of AATD. There were no differences seen in safety parameters (treatment emergent adverse events, serious adverse events, etc.) between the placebo and treatment groups during the double-blind and open-label extension periods. Two patients discontinued the study during the double-blind period, including one in the treated group, which was determined to be unrelated to treatment, and one in the placebo group.
“We strongly believe our inhaled AAT has the potential to change the treatment paradigm for AATD,” said Amir London, CEO of Kamada Ltd. “We intend to utilize the excellent results from this successful Phase 2 study to design a pivotal U.S. study and to support our responses to the EMA’s 120-day comments in regards to Kamada’s MAA for Inhaled AAT, which was submitted earlier this year. We also intend to continue our discussions with the U.S. Food and Drug Administration with this additional Phase 2 data and the data from our EU Phase 2/3 study in order to obtain guidance on the regulatory pathway for Inhaled AAT in the U.S.”
