Verastem to Seek FDA Approval for Duvelisib to Treat SLL and CLL After Consistently Positive Trial Results

Verastem to Seek FDA Approval for Duvelisib to Treat SLL and CLL After Consistently Positive Trial Results

Verastem‘s duvelisib significantly delays disease progression or death in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to Phase 3 trial results.

The trial, called DUO, showed that duvelisib maintained patients disease-free for a median of 13.3 months, while the standard of care – Novartis‘ Arzerra (ofatumumab) – kept the cancer at bay for 9.9 months. This represented a 48% reduction in the risk of disease progression or death.

The company is now planning to request FDA approval for duvelisib in the U.S. for the treatment of these patients.

“We remain on track to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) during the first quarter of 2018 requesting full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL and accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma (FL),” Diep Le, an MD and PhD, the chief medical officer of Verastem, said in a press release.

The study, “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,” was presented in December at the American Society of Hematology (ASH) 2017 Annual Meeting in Atlanta.

In the DUO trial (NCT02004522), patients were randomly assigned to receive either duvelisib or Arzerra. DUO’s primary goal was to determine if duvelisib lengthened the time a patient lived without disease progression. Secondary endpoints included overall response rate, overall survival, and safety measures.

Compared to Arzerra, duvelisib extended the median progression free survival for 13.3 months vs. 9.9 months, a highly significant result.

Patients with a high-risk mutation known as a 17p deletion also benefited more from duvelisib compared to Arzerra. In these patients, duvelisib led to a median progression-free survival of 12.7 months compared to 9.0 months in the control arm. This translated to a 49% reduction in their risk of progression or death.

The overall response rate was found to be significantly higher in the duvelisib group – 73.8% vs. 45.3%. Also, more patients in the duvelisib arm had a significant reduction (more than 50%) in the lymph node burden – 85% vs. 16%.

Among those who progressed while taking Arzerra, 89 patients were included in a subsequent crossover study where they received duvelisib. The robust activity of Verastem’s duvelisib was again confirmed, with 73% of patients responding to the treatment, with a median duration of response of 12.7 months. Patients remained alive and disease-free for a median of 15 months.

Duvelisib was found to be safe in the study’s participants. The most common severe adverse events were low neutrophil counts, a condition known as neutropenia, and anemia. Other adverse effects, not related to the blood characteristics, included diarrhea, pneumonia, and colitis.

Thirty-five percent of the patients in the DUO trial initially enrolled in duvelisib treatment discontinued the therapy due to an adverse event; 40 percent of the patients remained on Verastem’s duvelisib for more than 18 months, achieving a median total follow-up of almost two years.

“In the Phase 3 DUO study, oral duvelisib monotherapy achieved a statistically significant improvement in Progression-Free Survival (PFS) versus the approved standard of care treatment ofatumumab, along with a well characterized and manageable safety profile, in patients with previously treated CLL/SLL,” said Ian Flinn, MD and PhD, director of the Blood Cancer Research Program at Sarah Cannon Research Institute and lead investigator of the DUO study.

“Similar PFS advantages were also observed across all analyzed patient subgroups, including patients with 17p deletion, a genotype that historically correlates with poorer clinical outcomes,” Flinn said.

“Duvelisib also achieved a statistically significant improvement in Overall Response Rate (ORR) and significantly reduced lymph node burden in the vast majority of patients. These data are encouraging for patients with CLL/SLL who progress or relapse following initial treatment,” he added.