Infinity PhII results a blow for PI3K in inflammation
This article was originally published in Scrip
Infinity Pharmaceuticals has discontinued development of its oral PI3K inhibitor duvelisib in rheumatoid arthritis after the candidate failed in a Phase II trial.
The product was the most advanced in its class for inflammatory conditions across industry. It inhibits Class I phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma. PI3Ks are involved in multiple cellular processes including cell proliferation and survival, cell differentitation, cell migration and immunity.
Duvelisib's failure in Infinity's ASPIRA trial to meet the primary endpoint of ACR20 response (ie, the proportion of patients who achieve at least a 20% improvement in American College of Rheumatology (ACR) response criteria) after 12 weeks of study treatment marks a setback for this mechanism of action in the pharma industry's inflammation pipeline.
It leaves UCB with the most advanced program, with its Phase I oral PIK3-delta inhibitor UCB5857 under investigation for psoriasis, according to data gathered by Citeline's Pharmaprojects. The Belgian company had been planning to begin a Phase II study in early 2015. No other firm has a compound in clinical trials.
Infinity's trial evaluated 322 adults with active moderate to severe rheumatoid arthritis receiving a stable dose of methotrexate. It evaluated duvelisib dosed at 0.5mg, 1.0mg or 5.0mg twice daily with background methotrexate compared to treatment with placebo plus methotrexate. An effect of duvelisib compared with placebo was not observed on the primary endpoint at any of the three dose levels.
Duvelisib also failed to meet its primary endpoint in an exploratory Phase IIa trial in mild, allergic asthma in 2014, although at the time Infinity said the top line data were encouraging and showed early evidence of proof of activity. It said in October that the results of the ASPIRA trial together with the asthma data would inform its development strategy in inflammation. It now says that duvelisib "is unlikely to be pursued in any inflammatory indication", although it has a second PI3K-delta and gamma inhibitor called IPI-443.
"The team is continuing to analyze the data from the asthma study and will make a decision later this year about whether IPI-443 warrants further development in asthma," a spokesperson told Scrip. "If additional development of IPI-443 in asthma were to continue, it would likely be through partnering or out-licensing opportunities", they added.
Infinity continues to study duvelisib for the treatment of blood cancers with its partner AbbVie, and claims it has a potential best-in-class product (scripintelligence.com, 4 September 2014). Ongoing trials include the Phase II DYNAMO study in refractory indolent non-Hodgkin's lymphoma, DYNAMO+R, a Phase III study in patients with previously treated follicular lymphoma, and DUO, a Phase III study in relapsed/refractory chronic lymphocytic leukemia.
In oncology, there are numerous other PI3K inhibitors in development. Gilead Sciences' Zydelig (idelalisib), an oral PI3K-delta inhibitor, was approved in 2014 in the EU and US for chronic lymphocytic leukemia and non-Hodgkin's lymphoma.
For an interactive overview of key drugs in development and on the market for inflammatory conditions, grouped by mechanism of action, see Scrip's World of Inflammation dashboards.