Duvelisib Granted Positive EU Opinion for Relapsed/Refractory CLL and Refractory Follicular Lymphoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of single-agent duvelisib (Copiktra) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) following at least 2 prior therapies, and follicular lymphoma that is refractory to at least 2 prior systemic treatments.¹

“Today’s positive opinion from the CHMP is an important step on the path toward authorization in Europe for [duvelisib] which is expected to improve overall response rates in patients suffering from relapsed and/or refractory CLL and follicular lymphoma, who currently have limited treatment options,” David Cohan, MD, chief medical officer of Secura Bio, stated in a press release. “Assuming approval, [duvelisib] will provide patients and physicians across much of Europe with a treatment option that works differently from other available therapies for these incurable diseases.”

In the phase 3 DUO trial (NCT02004522), duvelisib resulted in a 60% reduction in the risk of disease progression or death compared with ofatumumab in patients with relapsed/refractory CLL/small lymphocytic lymphoma (SLL) who had previously received at least 2 lines of therapy.² The median progression-free survival (PFS) with duvelisib in this population was 16.4 months vs 9.1 months with ofatumumab (HR, 0.40).2 Additionally, in the phase 3 DYNAMO trial (NCT01882803), duvelisib elicited an overall response rate (ORR) of 42% in patients with follicular lymphoma.

In DUO, a total of 319 patients with CLL/SLL were randomized 1:1 to receive either duvelisib at a twice-daily dose of 25 mg until progressive disease or intolerable toxicity, or a 300-mg dose of ofatumumab on day 1, followed by 7 weekly infusions and 4 monthly infusions of 2000 mg.

In a subset of patients with CLL/SLL who had previously received at least 2 lines of therapy, 95 received duvelisib and 101 were given ofatumumab. The median patient age across this subset was 69 years, 88% had an ECOG performance status of 0 or 1, and 59% were male. Twenty-two percent of patients had a detected 17p deletion at baseline, while 52% had 1 or more tumors that were 5 cm or larger. Fifty-four percent of patients had previously received 3 or more lines of therapy, while 46% had received 2 prior lines.

Additionally, patients in the investigative arm had a median exposure to treatment of 13.0 months (range, 0.2-37.0), while those in the control arm had a median exposure of 5.0 months (range, <0.1-6). In this subset, duvelisib elicited an ORR of 78% compared with 39% with ofatumumab.

In DYNAMO, a total of 83 patients comprised the follicular lymphoma cohort; these patients were refractory to rituximab (Rituxan) and either chemotherapy or radioimmunotherapy. The median age in this subset was 64 years (range, 30-82), 68% were male, and 37% had bulky disease at baseline, defined as target lesions of 5 cm or larger. The majority, or 93%, had an ECOG performance status of either 0 or 1. The median prior lines of treatment was 3 (range, 1-10) and 94% of patients were refractory to their last therapy; 81% were refractory to at least 2 previous lines of treatment. Patients were exposed to treatment for a median of 5 months (range, 0.4-24).

Additional results indicated that 35 patients responded to treatment; this included 1 complete response and 34 partial responses. At 6 months, 43% of patients were still experiencing a response; 17% maintained their response at 12 months.

Regarding safety, the most frequent all-grade toxicities experienced with duvelisib include diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.

“The benefits of [duvelisib] are that it prolongs the survival time without any progression of the disease as compared to ofatumumab in patients with CLL who have received 2 or more prior lines of treatment and induces tumor responses in patients with follicular lymphoma who have received 2 or more prior treatment,” the EMA summary stated. “The most common adverse effects are respiratory tract infections, neutropenia, anemia, thrombocytopenia, headache, dyspnea, cough, decreased appetite, diarrhea/colitis, nausea, vomiting, abdominal pain, constipation, rash, musculoskeletal pain, arthralgia, pyrexia, fatigue, and increased transaminases.”

In September 2018, the FDA approved duvelisib for the treatment of patients with relapsed/refractory CLL/SLL or relapsed/refractory follicular lymphoma based on data from DUO and DYNAMO.

References

1. COPIKTRA (duvelisib) receives positive CHMP opinion for the treatment of relapsed and refractory CLL and refractory FL. News release. Secura Bio, Inc. April 1, 2021. Accessed April 1, 2021. https://prn.to/31B1xmm
2. Verastem Oncology receives FDA approval of COPIKTRA™ (duvelisib) capsules. News release. Verastem, Inc. September 24, 2018. Accessed April 1, 2021. https://bit.ly/2NDQm80