Verastem, with Phase 3 Results, to Request FDA Approve Oral Duvelisib to Treat Advanced CLL and SLL

Verastem, with Phase 3 Results, to Request FDA Approve Oral Duvelisib to Treat Advanced CLL and SLL

Verastem’s duvelisib was seen to outperform Arzerra (ofatumumab) in a Phase 3 trial of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the company announced.

The oral therapy nearly halved the risk of disease progression or death, and held patients progression-free for a median of 13.3 months. This was 3.4 months longer than in patients treated with Arzerra.

“Although the treatment of CLL/SLL has advanced in recent years, there remains a substantial unmet need with many patients progressing or relapsing following the available therapies,” Ian Flinn, MD, PhD, director of the Blood Cancer Research Program at Sarah Cannon Research Institute and the lead investigator on the study, said in a press release.

The trial (NCT02004522), called DUO after the drug’s dual mechanism of action, also showed that the treatment benefitted patients with a high-risk mutation known as a 17p deletion. These patients had a median progression-free survival of 12.7 months, compared to nine months among those given Arzerra.

“These positive results from the randomized DUO study demonstrate that duvelisib prolongs progression-free survival with a manageable safety profile in patients with relapsed or refractory CLL/SLL, including in high-risk patients with the 17p deletion,” said Flinn.

Duvelisib targets two enzymes involved in the growth of cancerous B- and T-cells. DUO had recruited 319 patients, and half received duvelisib while half were treated with the approved infusion therapy Arzerra.

“For our patients with CLL/SLL, and for the physicians who treat them, a convenient, oral monotherapy that is taken at home would be a valuable addition to the treatment landscape,” said Flinn.

The positive data will allow Verastem to seek regulatory approval for the drug. It plans to file a New Drug Application with the U.S. Food and Drug Administration (FDA) in the first half of 2018. The application will also include data from the Phase 2 DYNAMO study in patients with indolent non-Hodgkin’s lymphoma — a study that also achieved its primary endpoint with an overall response rate of 46 percent.

“We are extremely grateful to the patients, caregivers, and investigators who participated in the DUO study and we are pleased to be that much closer to delivering on our mission to develop drugs that improve the lives of patients with cancer,” said Robert Forrester, president and chief executive officer of Verastem.

“We anticipate sharing these results with the FDA in preparation for a potential NDA filing during the first half of 2018 and look forward to exploring subsequent development opportunities for duvelisib in additional cancers.”

One of these cancers is peripheral T-cell lymphoma. On Sept. 6, Verastem also announced that it will expand its duvelisib development program to include patients with this lymphoma who have failed at least one earlier treatment.

A Phase 1 study in peripheral T-cell lymphoma patients demonstrated an overall response rate of 50 percent in 16 heavily pre-treated patients with relapsed or refractory disease. Nineteen percent had a complete response, and the remaining 31 percent had partial responses.

The data has spurred the company to initiate an open-label, Phase 2 trial that will evaluate the efficacy and safety of duvelisib in patients with relapsed or refractory peripheral T-cell lymphoma. The study, which will launch before year’s end, will be conducted in both the U.S. and Japan. The therapy has received Fast Track designation from the FDA.

“PTCL [peripheral T-cell lymphoma] is a rare and usually aggressive type of NHL [non-hodgkin lymphoma] where currently available therapies only provide modest benefit,” Forrester, said in a press release.

“We believe an oral monotherapy like duvelisib could be an important new treatment alternative for patients with T-cell lymphomas, including PTCL, and we look forward to initiating a Phase 2 study in patients with relapsed or refractory disease by year end,” he added.

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