Humanigen’s Inflammation Therapy Is Only Modestly Effective in CF Patients with an Infection, Trial

Humanigen’s anti-inflammatory therapy KB001-A is safe but only modestly effective in cystic fibrosis patients with a Pseudomonas aeruginosa bacteria infection, a Phase 2 clinical trial indicates.

In addition to displaying limited ability to decrease markers of patients’ lung inflammation, it failed to generate substantial decreases in their bacteria levels or improvements in their lung function, researchers said.

The therapy works by trying to prevent bacteria from releasing toxins that generate inflammation.

Researchers’ study, “KB001-A, a novel anti-inflammatory, found to be safe and well-tolerated in cystic fibrosis patients infected with Pseudomonas aeruginosa,” was published in the Journal of Cystic Fibrosis.

Lung inflammation and infections are hallmarks of CF that scientists believe account for the disease’s progressive lung damage.

One of the most common bacteria in CF patients’ airways is Pseudomonas aeruginosa, which affects about 80 percent of adults with the disease. A mainstay of treatment against it is antibiotics.

Scientists say a protein called PcrV is involved in the inflammation seen in CF patients’ lungs. It is present at the tip of P. aeruginosa’s secretion system, which releases toxins into a patient’s body, leading to inflammation and damage.

KB001-A is an antibody aimed at preventing PcrV from helping bacteria release the toxins that contribute to inflammation.

Animal studies indicated that it can help protect against P. aeruginosa-triggered lung inflammation.

Phase 1-2 clinical trials (NCT00638365 and NCT00691587) showed it to be safe and well-tolerated, generating no life-threatening adverse events. It led to no significant reduction in P. aeruginosa levels or improvements in lung function, although it did reduce inflammatory markers.

Humanigen conducted a Phase 2 clinical trial (NCT01695343) to try to confirm or extend the previous trials’ findings. It indicated that KB001-A reduced the lung inflammation of CF patients with a chronic P. aeruginosa airway infection.

Patients received infusions of the therapy or a placebo at the start of the study and at weeks 2, 4, 8, and 16. To get a handle on its effectiveness, researchers assessed inflammation markers in the patients’ lungs.

KB001-A was safe and well-tolerated compared with a placebo, researchers found. There was only one serious adverse event — an elevation of one patient’s liver enzymes for reasons that were unclear.

Patients who received KB001-A tripled their scores on a lung function measure known as FEV1 at week 16, compared with the placebo group. FEV1 is the amount of air a person can exhale in a second after taking a deep breath.

Another finding was that levels of the inflammation marker IL-8 were significantly lower in the KB001-A group than in the placebo group.

Taken together, the results showed that “KB001-A was safe and well-tolerated and associated with a modest FEV1 benefit and reduction in select [lung] sputum inflammatory markers (IL-8),” the researchers wrote.