The FDA has granted a priority review to a new drug application (NDA) for duvelisib for a full approval for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and an accelerated approval for the treatment of patients with relapsed/refractory follicular lymphoma.
The NDA includes supporting data from the phase III DUO trial and the phase II DYNAMO study. In DUO, duvelisib reduced the risk of disease progression or death by 48% versus ofatumumab (Arzerra) in patients with relapsed/refractory CLL/SLL. In the overall population, the median progression-free survival (PFS) with the PI3K-delta and -gamma inhibitor was 3.4 months longer with duvelisib compared to ofatumumab. In patients with a 17p deletion (del[17p]), the median PFS benefit was 3.7 months.
In the DYNAMO study, duvelisib demonstrated an overall response rate (ORR) of 46% (P
<.0001) for patients with indolent non-Hodgkin lymphoma (iNHL), including 41% in patients with follicular lymphoma.
Under the priority designation, the FDA will review the NDA within 6 months from the acceptance of the filing, compared with the standard 10 months. The FDA is scheduled under the Prescription Drug User Fee Act to make its decision by October 5, 2018.
“Obtaining priority review in the United States for duvelisib marks another important milestone for Verastem and speaks to the unmet need in relapsed/refractory CLL/SLL and FL and the urgency to identify effective therapies to treat these patients,” Robert Forrester, president and CEO of Verastem, the manufacturer of duvelisib, said in a statement.
“As an orally administered therapy, we believe duvelisib will provide an important treatment option for patients with CLL/SLL and follicular lymphoma, and for the physicians who treat them. We look forward to working with the FDA during the review process,” added Forrester.
The phase III DUO study randomized 319 patients with CLL/SLL in a 1:1 ratio to duvelisib at 25 mg twice daily until disease progression or unacceptable toxicity, or ofatumumab at 300 mg on day 1, followed by 7 weekly infusions and 4 monthly infusions of 2000 mg.
The median PFS was 13.3 months in the duvelisib arm compared with 9.9 months in the ofatumumab arm (hazard ratio [HR], 0.52; P
<.0001). In patients with del(17p), the median PFS was 12.7 versus 9.0 months, respectively (HR, 0.41; P
In the overall population, the ORR with duvelisib was 73.8% versus 45.3% with ofatumumab (P <.0001) and lymph-node burden was reduced by more than half in 85% versus 16% of patients, respectively. Among patients with del(17p), the ORR was 70.0% versus 43.0% with duvelisib versus ofatumumab, respectively (P
= .0182). In the intent-to-treat population, overall survival (OS) between the 2 arms was similar (HR, 0.99; P
The median time on treatment was 50.3 weeks (range, 0.9-160.0) versus 23.1 weeks (range, 0.1-26.1) in the duvelisib and ofatumumab arms, respectively. The most common grade ≥3 adverse events (AEs) in the duvelisib group were neutropenia (30%) and anemia (13%). The most frequent nonhematologic grade ≥3 AEs were diarrhea (15%), pneumonia (14%), and colitis (12%). There were 4 patient deaths associated with duvelisib treatment-related AEs: general physical health deterioration (n = 1), pneumonia staphylococcal (n = 2), and sepsis (n = 1).
The open-label phase II DYNAMO study, which began enrolling in May 2013, included patients with iNHL who were refractory to rituximab (Rituxan) and either chemotherapy or radioimmunotherapy. Among the 129 enrolled patients, the disease types included follicular lymphoma (n = 83), SLL (n = 28), and marginal zone lymphoma (n = 18). Continuous duvelisib was administered at 25 mg twice daily.
The ORRs in the follicular lymphoma, SLL, and marginal zone lymphoma groups were 41%, 68%, and 33%, respectively. The median duration of response was 9.9 months. At a median follow-up of 11.5 months, the median OS in the entire iNHL population was 18.4 months and the median PFS was 8.4 months.
The most common grade ≥3 AEs were neutropenia (23%), anemia (12%), thrombocytopenia (10%), and diarrhea (15%). Seventeen percent of patients discontinued duvelisib due to an AE. There were 6 patient deaths related to AEs.
Verastem submits new drug application to US FDA for duvelisib for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma. Verastem. Published February 7, 2018, Accessed April 9, 2018. http://bit.ly/2GT3m2u.