Infinity reports topline data from phase 2a exploratory study of duvelisib in asthma patients

Data from this randomized, double-blind, placebo-controlled, cross-over study demonstrated that duvelisib was well tolerated and met several secondary and exploratory endpoints in an allergen challenge study.

Clinical improvement was observed in the late-phase asthmatic response FEV1 (a standard lung function test that measures the amount of air that can be exhaled in one second) among patients who received duvelisib administered at the highest dose tested, 25 mg twice daily (BID) for five days; however the primary endpoint of the study was not met as it did not reach statistical significance (p = 0.052).

Multiple secondary clinical endpoints measuring improvements in lung function following duvelisib administration were achieved with statistical significance and were associated with changes in key cytokines and chemokines involved in the asthmatic response. Taken together, these data demonstrate early proof-of-activity in this allergen challenge study.

"This is the first clinical study to suggest that inhibition of PI3K-delta and PI3K-gamma plays a role in improving lung function for patients with asthma. In this exploratory study, duvelisib showed evidence of activity across several important clinical measures, including improvement in the late-phase asthmatic response and significant corresponding changes in several key mediators of airway inflammation," stated Julian Adams, Ph.D., president of research and development at Infinity.

"These data support further development of PI3K-delta,gamma inhibitors in more severe forms of asthma, for which there is a medical need."

"In addition to asthma, we are also studying duvelisib for the treatment of rheumatoid arthritis. We expect to report data from ASPIRA, Infinity’s Phase 2 study of duvelisib with background methotrexate in patients with moderate-to-severe rheumatoid arthritis, by the end of the year. The results of both clinical studies will inform Infinity’s development strategy for its PI3K-delta,gamma program in inflammation," Dr. Adams continued.

The Phase 2a, randomized, double-blind, placebo controlled, exploratory study was designed to evaluate the activity and safety of duvelisib in 50 patients with mild, allergic asthma following an inhalational allergen challenge.

Patients were randomized to receive treatment with placebo followed by duvelisib or duvelisib followed by placebo in a two-period cross-over design, with duvelisib administered at either 1 mg BID (n = 14) or 5 mg BID for 14 days (n = 18), or 25 mg BID for five days (n = 18). The study included a washout period between the two treatment periods of this cross-over study, in which each patient serves as his own control.

The study primary endpoint of significantly improving the maximum early-phase or late-phase asthmatic response as measured by FEV1 was not met at any of the doses tested.

However, clinical improvement in the late-phase response was observed at the 25 mg BID dose (p = 0.052) and multiple secondary efficacy endpoints were significantly positive at the 25 mg BID dose, including an improvement in FEV1 AUC (area under the curve) over the entire assessment period (p = 0.013) and a decrease in patients’ sensitivity to methacholine treatment, a measure of airway hyper-reactivity (p = 0.036).

Additionally, the 5 mg BID and 25 mg BID doses of duvelisib significantly decreased serum levels of key mediators of airway inflammation.

In the study, duvelisib was well tolerated at all three dose levels studied. No serious adverse events were reported, and there were no clinically significant safety findings.

Infinity expects to present the final data in a peer-reviewed setting after all analyses are complete. In addition, the company anticipates determining its next steps for development of PI3K-delta,gamma inhibitors in inflammation after evaluating the results from the ASPIRA study in rheumatoid arthritis, which are expected by the end of 2014.

The PI3Ks are a family of enzymes involved in multiple cellular functions, including cell proliferation and survival, cell differentiation, cell migration and immunity.

The Class 1 PI3K-delta and PI3K-gamma isoforms are preferentially expressed in leukocytes (white blood cells), where they have distinct and predominantly non-overlapping roles in key cellular functions, including cell proliferation, cell differentiation, cell migration and activation. Targeting PI3K-delta and PI3K-gamma may provide multiple opportunities to develop differentiated therapies for the treatment of hematologic malignancies as well as inflammatory diseases.