ORLANDO, Fla. – Treating previously untreated older patients with chronic lymphocytic leukemia (CLL) with Imbruvica (ibrutinib) proved superior to standard of care treatment with the chemotherapy chlorambucil, according to new phase III data presented at the American Society of Hematology meeting and simultaneously published online in The New England Journal of Medicine.

The Resonate-2 (PCYC-1115) study found that Imbruvica significantly decreased the risk of disease progression or death and significantly decreased the risk of death vs. chemotherapy in treatment-naïve patients 65 years and older with CLL. It also significantly improved hematologic function as measured by sustained improvements in hemoglobin and platelets. The trial was the first late-stage head-to-head study in the program to evaluate the safety and efficacy of ibrutinib vs. traditional chemotherapy for such patients and is a key element of Abbvie Inc.'s effort to secure approval to market the drug for the treatment of a much larger slice of the current 115,000 patients in the U.S. with the condition. As of now, it only has approval to treat patients who have a genetic aberration that occurs when part of chromosome 17, the location of the tumor suppressor gene p53, has been lost or deleted.

Imbruvica is jointly developed and commercialized in the U.S. by Pharmacyclics LLC, part of Abbvie, and Janssen Biotech Inc., part of Johnson & Johnson.

"Chemotherapy is the standard means to treat patients with CLL and follicular lymphoma, but it's not curing anyone," Danelle James, head of oncology at Pharmacyclics told BioWorld Today. With Resonate-2, she said, doctors could potentially gain a new broad front-line tool that could help many more patients.

Ibrutinib significantly prolonged progression-free survival during the study, reducing the risk of progression or death by 84 percent vs. chlorambucil (hazard ratio 0.16; p<0.001), with a median of 18.4 months of follow-up. The 18-month PFS rate was 90 percent vs. 52 percent, respectively. Additionally, ibrutinib significantly prolonged overall survival (hazard ratio, 0.16; p=0.001) with an estimated survival rate of 98 percent at 24 months, compared to 85 percent with chlorambucil. Ibrutinib was also associated with a significantly higher overall response rate of 86 percent vs. 35 percent for chlorambucil (p<0.001), with a trend toward increased complete response rates.

"We've never seen survival rates like this before," Mark Wildgust, global medical affairs head of hematology for Janssen told BioWorld Today. "The earlier ibrutinib is used in the treatment spectrum, it seems like the results get better and better. The survival curve doesn't seem like a curve anymore. It's flat."

The data build on earlier insights into the Bruton's tyrosine kinase (Btk) inhibitor gathered during RESONATE, a head-to-head comparison of Imbruvica vs. Arzerra (ofatumumab) in patients with relapsed or refractory CLL or relapsed or refractory small lymphocytic lymphoma that served as the basis for Imbruvica's original approval. In September, a supplemental new drug application was submitted to the FDA for use of the drug in treatment-naive CLL patients based on data from RESONATE-2.

The most common adverse events (AE) during Resonate-2 for ibrutinib were diarrhea, fatigue, cough and nausea; AEs for chlorambucil included nausea, fatigue, neutropenia and vomiting. Overall, adverse events leading to treatment discontinuation were less frequent with ibrutinib than with chlorambucil.

Another phase III study, RAY, pitting Imbruvica against temsirolimus in relapsed or refractory mantle cell lymphoma patients found that Imbruvica significantly prolonged progression-free survival and improved overall response rates for those patients, After a median follow-up of 20 months, Imbruvica was associated with a 57 percent reduction in the risk of progression or death and 42 percent of Imbruvica patients died vs. 45 percent of patients who received temsirolimus.