The new drug application submitted to the U.S. Food and Drug Administration (FDA) also requests the accelerated approval of duvelisib, a PI3K inhibitor, for treating relapsed or refractory follicular lymphoma.
“We are immensely grateful to all of the patients that participated in the duvelisib clinical trialprogram over the last few years,” Robert Forrester, president and CEO of Verastem, said in a press release.
Duvelisib is a molecule that inhibits PI3K-delta and PI3K-gamma, two enzymes that are believed to help malignant B- and T-cells survive and grow. By disrupting B- and T-cells’ interactions with their microenvironment, duvelisib weakens them and stops tumor growth.
The therapy candidate received fast track designation from the FDA in September 2017 for patients with CLL or peripheral T-cell lymphoma (PTCL) who received at least one prior therapy, and for patients with follicular lymphoma who have received at least two prior therapies.
The recent application was based on data from the DUO Phase 3 clinical trial (NCT02004522), a study that demonstrated the effectiveness of duvelisib, along with a consistent and manageable safety profile in patients with relapsed/refractory CLL/SLL.
In the DUO study, duvelisib extended the time a patient remained without disease progression from 9.9 months – seen with standard of care Arzerra (ofatumumab) – to 13.3 months. The significant result was accompanied by evidence that patients with a 17p deletion (a high-risk mutation) benefited more from duvelisib than Arzerra.
In these patients, duvelisib led to a median progression-free survival of 12.7 months versus 9.0 months in the control arm, translating to a 49 percent reduction in their risk of progression or death.
Overall response rate also was higher in the duvelisib group (73.8 versus 45.3 percent) and more than half the patients on duvelisib had a significant reduction in the lymph node burden (85 percent versus 16 percent).
Results from the study were presented in December at the American Society of Hematology (ASH) 2017 Annual Meeting in Atlanta, under the title “Results from the Phase 3 DUO Trial: A Randomized Comparison of Duvelisib Vs Ofatumumab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma.”
Results from the ongoing DYNAMO Phase 2 clinical trial (NCT01882803), which included patients with refractory indolent non-Hodgkin lymphoma (NHL), also supported the application.
Preliminary results from the DYNAMO trial suggest the candidate achieved important clinical activity in heavily pre-treated and highly refractory indolent NHL patients, with an acceptable safety profile.
The study achieved its primary goal with an objective response rate of 46 percent. In the subset of patients enrolled in DYNAMO with double-refractory follicular lymphoma, 41 percent achieved at least a partial response with duvelisib.
These preliminary findings were presented at the 14th International Conference on Malignant Lymphoma (ICML), held June 14 to 17 in Lugano, Switzerland, under the title “DYNAMO: A Phase 2 Study Demonstrating the Clinical Activity of Duvelisib in Patients with Double-Refractory Indolent Non-Hodgkin Lymphoma.”