Date: 2014-10-16
Type of information: Results
phase: 2a
Announcement: results
Company: Infinity Pharmaceuticals (USA - MA)
Product: duvelisib (IPI-145)
Action
mechanism: phosphoinositide 3-kinase (PI3K) inhibitor. Duvelisib is an oral inhibitor of Class I PI3K-delta,gamma. The PI3Ks are a family of enzymes involved in multiple cellular functions, including cell proliferation and survival, cell differentiation, cell migration and immunity. The PI3K-delta,gamma isoforms are preferentially expressed in leukocytes (white blood cells), where they have distinct and mostly non-overlapping roles in immune cell development and function. Targeting PI3K-delta and PI3K-gamma may provide multiple opportunities to develop differentiated therapies for the treatment of hematologic malignancies. Infinity and AbbVie Inc. are developing duvelisib, an oral inhibitor of Class I PI3K-delta,gamma. 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, or 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. In 2013, Infinity launched the DUETTS™ (Duvelisib Trials in Hematologic Malignancies) program, a worldwide investigation of duvelisib in blood cancers. As part of the DUETTS program, patient enrollment is ongoing in DYNAMO™, a Phase 2 monotherapy study designed to evaluate the safety and efficacy of duvelisib in patients with refractory indolent non-Hodgkin lymphoma (iNHL) (NCT01882803), and DUO™, a Phase 3 monotherapy study designed to evaluate the safety and efficacy of duvelisib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) (NCT02004522). DYNAMO+RTM, a Phase 3 study of duvelisib in combination with rituximab in patients with previously treated follicular lymphoma (NCT02204982), is expected to start in 2014. Additionally, a Phase 1 study of duvelisib in patients with advanced blood cancers is ongoing (NCT01476657).
Disease: mild, allergic asthma
Therapeutic area: Allergic diseases - Inflammatory diseases - Respiratory diseases
Country:
Trial
details: 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.
Latest
news: * On October 16, 2014, Infinity Pharmaceuticals announced topline data from its Phase 2a exploratory study of duvelisib (IPI-145), its oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in patients with mild, allergic asthma. 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. 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. 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. 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.
