WASHINGTON -- The FDA approved the dual PI3K inhibitor duvelisib (Copiktra) on Monday for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma, drugmaker .
"Copiktra is an important addition to the evolving treatment paradigm for patients with CLL/SLL and follicular lymphoma," Ian Flinn, MD, PhD, of the Sarah Cannon Research Institute in Nashville, Tennessee, said in Verastem's .
Flinn, who was lead investigator of the trials that led to the approvals, called duvelisib a "significant addition to physicians' treatment armamentarium" for patients who have progressed after two prior therapies.
The indication for CLL/SLL came from the multicenter open-label DUO trial that compared duvelisib to ofatumumab. The study randomized patients to oral 25-mg duvelisib twice daily or ofatumumab, which is administered intravenously in a 6-week course.
Among patients that had received two prior therapies (n=196), median progression-free survival favored duvelisib (16.4 versus 9.1 months with ofatumumab), as did the rate of overall response (78% versus 39%, respectively).
Susan O'Brien, MD, of the University of California Irvine, said that duvelisib -- the first approved PI3K-delta and PI3K-gamma inhibitor -- might be "stigmatized" by clinicians' experience with the PI3K-delta inhibitor idelalisib (Zydelig).
"If you look at the toxicity profile for [duvelisib] from a qualitative point of view it doesn't look very different than idelalisib in terms of transaminitis, pneumonitis, colitis," O'Brien said in an interview with 51˶ prior to Monday's approval. "However, if you look from a quantitative point of view it appears to be less -- with the caveat that there are a lot less patients exposed to [duvelisib] and so smaller numbers and wider confidence intervals -- but it appears to be less."
Idelalisib, a first-in-class PI3K delta inhibitor, burst on the scene with a trio of blood cancer approvals in 2014 -- also CLL/SLL and follicular lymphoma -- but its use has been hampered by dose-limiting toxicities.
"There is a rationale for why inhibiting gamma in addition to delta might reduce the toxicity," O'Brien added.
The approval for follicular lymphoma was based on 83 patients from the single-arm DYNAMO study, which yielded an overall response rate of 42% (95% CI 31%-54%) in duvelisib-treated patients who were refractory to rituximab and either radioimmunotherapy or chemotherapy.
There was one complete response, and 34 partial responses. Of these, 43% had a duration of response of 6 months or more and 17% had responses of a year or longer.
Common adverse events (20% or more) seen in DYNAMO and DUO included anemia, cough, colitis or diarrhea, rash, neutropenia, fatigue, pyrexia, nausea, upper respiratory infection, musculoskeletal pain, and pneumonia. Dose reductions were required in 24% of patients and 35% of patients discontinued the drug due to adverse events.
Serious adverse events occurred in 65% of patients with various blood cancers treated with the drug at the approved dose. The drug will carry a boxed warning due to the risk of fatal and/or serious infections, diarrhea or colitis, skin reactions, and pneumonitis, as well as warnings of neutropenia and hepatotoxicity.