a global biopharmaceutical company, announced today that it submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) based on the randomized, multi- center, open-label Phase III RESONATETM-2 (PCYC-1115) trial assessing the use of IMBRUVICA® (ibrutinib) versus chlorambucil in treatment-naive chronic lymphocytic leukemia (CLL) patients aged 65 years or older. AbbVie announced top-line findings from the trial in June 2015 showing that IMBRUVICA improved progression-free survival (PFS; primary endpoint) and multiple secondary endpoints including overall survival (OS) and overall response rate (ORR) in treatment-naive patients with CLL. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc.
“This submission highlights the expanded potential and strong value of IMBRUVICA as a treatment for CLL,” said Erik von Borcke, President of Pharmacyclics. “We are pleased treatment-naive patients may soon have an alternative to traditional cytotoxic chemotherapy.”
IMBRUVICA is currently approved for the treatment of patients with CLL who have received at least one prior therapy and CLL patients (including treatment-naive) who have del 17p, a genetic aberration that occurs when part of chromosome 17, the location of the tumor suppressor gene p53, has been lost or deleted.
The data have been submitted for publication in a peer-reviewed journal and presentation at an upcoming medical conference.
The RESONATE-2 trial is a Pharmacyclics-sponsored study and its protocol and specific performance goals were established in a special protocol assessment (SPA) with the FDA. A SPA is an agreement with the FDA that a Phase III clinical trial design, its clinical endpoints and statistical analyses are acceptable to the Agency to support a submission and potential approval. The trial enrolled 269 treatment-naive patients with CLL or small lymphocytic lymphoma (SLL) aged 65 years or older in the U.S., EU and other regions. Patients were randomized to receive either ibrutinib 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in Cycle 1 was 0.5 mg/kg and was increased based on tolerability in Cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg. The primary endpoint of the study was PFS as assessed by an Independent Review Committee according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis. Key secondary endpoints included ORR, OS and safety.
About Chronic Lymphocytic Leukemia (CLL)
The prevalence of CLL/SLL is approximately 115,000 patients in the United States,i with approximately 16,000 newly diagnosed patients every year.ii As this orphan disease frequently progresses following treatment with existing first-line therapies, patients are faced with fewer treatment options and often are prescribed multiple lines of therapy as they relapse or become resistant to current standard of care treatments.
In CLL/SLL, the genetic aberration del 17p occurs when part of chromosome 17, the location of the tumor suppressor gene p53, has been lost or deleted. CLL/SLL patients with del 17p have poor treatment outcomes.iv Del 17p is reported in approximately 7% of treatment-naive CLL/SLL cases,v and approximately 20% to 40% of relapsed/refractory patients harbor the mutation.