Secura Bio withdraws its indication for relapsed / refractory follicular lymphoma from Duvelisib in the United States


Secura Bio, Inc. has decided to voluntarily withdraw the indication for duvelisib (Copiktra) for use in patients with relapsed or refractory follicular lymphoma following at least 2 previous systemic treatments.1

The FDA granted expedited approval to the agent for use in patients with relapsed / refractory chronic lymphocytic leukemia / small lymphocyte leukemia (CLL / SLL) or relapsed / refractory follicular lymphoma in September 2018 on the basis of data from the DUO phase 3 trial (NCT02004522) and the DYNAMO phase 2 trial (NCT01882803).2

DUO results showed that duvelisib resulted in a 60% reduction in the risk of disease progression or death compared to ofatumumab (Arzerra) in patients with relapsed / refractory CLL / SLL who had previously received at least 2 treatment lines. The median progression-free survival (PFS) was 16.4 months in the investigation arm versus 9.1 months in the control arm (RR: 0.40). Duvelisib elicited a 78% ORR versus 39% with ofatumumab.

DYNAMO data indicated that the agent elicited an overall response rate (ORR) of 42% (95% CI, 31% to 54%) in patients with follicular lymphoma. The duration of response ranged from 0 months to 41.9 months; 43% of patients maintained their response at 6 months and 17% continued to respond at 12 months.2

The indication for follicular lymphoma was accompanied by a requirement that additional confirmatory testing would be required for the product to receive full approval.

Secura Bio conducted a strategic assessment of duvelisib and then consulted with the regulatory agency to discuss the indication. The company decided that the current paradigm for treating follicular lymphoma in the United States, as well as the logistics, cost, and timing of postmarketing requirements for duvelisib in this disease are no longer warranted.

“Secura Bio has determined that a more careful application of future efforts and resources is in a new application for T cell lymphoma where the initial data looks encouraging,” the company said in a press release. “The company looks forward to working with the FDA and seeking advice on an appropriate regulatory and clinical plan.”

The open-label, multicenter, phase 3 DUO trial enrolled 319 patients with CLL (n = 312) or SLL (n = 7) who had received at least one treatment.2 To be eligible for enrollment, patients had to have liver failure. transaminases ≤ 3 times the upper limit of normal (ULN), total bilirubin ≤ 1.5 times the ULN and serum creatinine ≤ 2 times the ULN. Those who had already undergone an autologous transplant within 6 months or an allogeneic transplant, or who had previously been exposed to a PI3K inhibitor or a BTK inhibitor, were excluded.

Study participants were randomized 1: 1 to receive either duvelisib at a dose of 25 mg twice daily until disease progression or intolerable toxicity, or ofatumumab for 7 cycles. People in the control group received ofatumumab at an initial dose of 300 mg, followed 1 week later by 2000 mg once a week for 7 doses, then 2000 mg once a week for 4 additional doses.

In a subset of patients, 95 who received duvelisib and 101 who received ofatumumab, the median age was 69 years (range: 40-90), 59% were males and 88% had an index of ECOG performance of 0 or 1. In addition, 46% of patients have already received 2 prior lines of treatment and 54% have received 3 prior lines of treatment. Fifty-two percent of patients had at least one tumor measuring 5 cm or more at baseline, and 22% of patients had tumors with a 17p deletion.

The main criteria for evaluating effectiveness focused on the PFS by independent review committee and on the ORR.

Patients in the investigation arm had a median exposure to duvelisib of 13 months (range, 0.2-37). Eighty percent of patients received at least 6 months of treatment with the agent and 52% received the agent for at least 1 year. Patients in the control group had a median drug exposure of 5 months (range,

The safety analysis of the trial included the total study population, which consisted of 313 patients who received treatment; of these patients, 158 received duvelisib and 155 received ofatumumab. The most commonly reported side effects with duvelisib, which were reported in 20% or more of patients, included diarrhea or colitis, neutropenia, fever, upper respiratory tract infections, pneumonia, rash, fatigue, nausea, anemia and cough.

Twelve percent of patients who received duvelisib experienced fatal side effects compared to 12% of those who received ofatumumab. Seventy-three percent of patients who received duvelisib experienced serious side effects; 38% of these patients developed infection and 23% reported diarrhea or colitis.

Twenty-nine percent of patients in the investigational arm required dose reductions due to toxicities. In addition, 36% of patients discontinued treatment with duvelisib, mainly due to diarrhea or colitis, infection and rash.

The single-arm, multicenter DYNAMO trial included patients previously treated with follicular lymphoma who were refractory to rituximab (Rituxan) and chemotherapy or radioimmunotherapy. Patients with grade 3b follicular lymphoma, large cell transformation, or previously allogeneic transplant or previously exposed to a PI3K or BTK inhibitor were excluded.

Study participants received duvelisib at a dose of 25 mg twice daily (n = 83). The median age of these patients was 64 years (range: 30-82), 68% were males, and 37% had bulky disease at baseline. Additionally, the median number of prior lines of treatment received was 3 (range, 1-10), and 94% were refractory to their last treatment. Eighty-one percent of patients were refractory to 2 or more previous lines of treatment. In addition, 93% of patients had an ECOG performance index of 0 or 1.

Participants who received duvelisib had a median exposure of 5 months (range, 0.4-24); 41% of patients received the agent for at least 6 months and 10% received it for at least 1 year.

Safety was evaluated in 96 patients with relapsed or refractory follicular lymphoma who received duvelisib; these patients were included in a safety analysis of 442 patients. Serious toxicities were reported in 58% of patients and included diarrhea or colitis, pneumonia, renal failure, rash, and sepsis.

The most common toxicities were diarrhea or colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, fever, headache, mucositis, abdominal pain, vomiting, elevation of transaminases and thrombocytopenia.

Twenty-nine percent of patients discontinued duvelisib treatment due to toxicities, and this occurred most often due to diarrhea or colitis and rash. Twenty-three percent of patients required dose reductions due to side effects.

The decision to withdraw the application was not associated with changes in the safety and effectiveness of the agent, according to Secura Bio, Inc. The decision only affects the U.S. indication of the agent in relapsed / refractory follicular lymphoma and does not affect other approved indications for the agent in the United States and other countries, including use in adult patients with SLL or relapsed or refractory SLL following at least 2 previous treatments.

The references

  1. Secura Bio announces the strategic focus of Copiktra (duvelisib) on T cell lymphoma and the voluntary withdrawal in the United States of the indication for relapsed or refractory follicular lymphoma. Press release. Secura Bio, Inc .; December 3, 2021. Accessed December 6, 2021. https://prn.to/31zvqH8
  2. Copiktra. Prescribing information. Secura Bio, Inc .; 2021. Accessed December 6, 2021. https://copiktra.com/pdf/COPIKTRA-PI-USCPR2007402.pdf

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