Pharmacyclics' Reply

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We acknowledge the letters submitted to The ASCO Post from a patient advocate and a chronic lymphocytic leukemia (CLL) patient enrolled on the RESONATE study (PCYC-1112-CA).

At Pharmacyclics, we are committed to adhering to high scientific and ethical standards as we strive to develop novel therapies that help patients with unmet medical needs. RESONATE was the first randomized study in the ibrutinib clinical program. Prior to any patient receiving treatment on this clinical trial, the PCYC-1112 protocol was reviewed and approved by health-care authorities, ethics committees, institutional review boards, and signed off by the principal investigator at each clinical site.

RESONATE was designed with guidance from health authorities and advisors to evaluate the potential benefit of ibrutinib in comparison with an appropriate control, ofatumumab (Arzerra), in relapsed or refractory CLL patients for global registration. Although crossover was not a procedure in the original PCYC-1112 protocol, in December 2012, Pharmacyclics (as the sponsor of the study) released an amendment that would provide access to ibrutinib for patients randomized to ofatumumab once (and if) the favorable benefit-to-risk ratio of ibrutinib over the control group has been demonstrated and following discussion and agreement with the health authority around the critical issues of patient safety and efficacy.

Protocol Update

Since that time, additional phase I/II data have emerged and the durability of response to ibrutinib for CLL patients is now better understood. Based on these mature data and with the recommendation of our Steering Committee, we have since approached global health-care authorities and the independent Data Monitoring Committee (DMC) with a plan to allow for earlier access to ibrutinib for patients who were randomly assigned to the control arm than was previously planned.

Discussions with the Food and Drug Administration confirmed that the agency supports crossing ofatumumab treated patients on PCYC-1112 to ibrutinib treatment once disease progression has been confirmed by the Independent Review Committee (IRC), a process that will preserve the primary endpoint of IRC-assessed progression-free survival. It is our fervent hope and goal that the results of the trial demonstrate sufficient patient benefit such that global regulatory authorities consider ibrutinib worthy of a defined label.

On August 8, 2013, we released an amendment to the RESONATE study that allows crossover to ibrutinib treatment for patients who have shown disease progression on ofatumumab. Pharmacyclics maintains its relentless focus on bringing worldwide access to ibrutinib for patients who may receive benefit from this drug. For CLL patients on the control arm of PCYC-1112, we have worked continuously and tirelessly to implement this important study design change.

We know full well that patients are waiting. We at Pharmacyclics feel it is both an honor and obligation to reach patients in need as soon as possible. ■

—Danelle James, MD, MS
Senior Medical Director, Pharmacyclics
—Jesse McGreivy, MD
Chief Medical Officer, Pharmacyclics