Pharmacyclics announces positive results from IMBRUVICA Phase II study in WM patients

Pharmacyclics, Inc. (NASDAQ: PCYC) today announced longer-term data from a Phase II investigator-initiated study showing Waldenstrom's macroglobulinemia (WM) patients treated with IMBRUVICA^® (ibrutinib) experienced sustained disease control with an overall response rate (ORR) of 91% after a median of 19.1 months of treatment and a 2-year overall survival (OS) rate of 95%. These updated results were published last night online in The New England Journal of Medicine (NEJM). An earlier analysis of the data served as the basis for the January 2015 U.S. Food and Drug Administration approval of IMBRUVICA for the treatment of all patients with WM. IMBRUVICA is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

"The results are remarkable when you consider that patients had received an average of two prior therapies, and 40% showed no response to the previous treatments," said lead investigator Steven P. Treon, M.D., Ph.D., Director of the Bing Center for Waldenstrom's Macroglobulinemia at the Dana-Farber Cancer Institute and Associate Professor at Harvard Medical School, Boston, Mass. "The findings herald a new era for the treatment of Waldenstrom's macroglobulinemia."

The Phase II, prospective, open-label, multi-center study evaluated the safety and tolerability of IMBRUVICA 420 mg orally, once daily until disease progression or unacceptable toxicity in 63 previously treated patients who had received a median of two prior therapies (range 1-9). The primary endpoint was ORR, which was defined as a sum of minor (MR), partial (PR), very good partial (VGPR) and complete responses (CR), as well as major (PR+VGPR+CR) response rates as assessed by investigators and an independent review committee (IRC) using criteria adopted from the International Workshop of Waldenstrom's Macroglobulinemia. Secondary endpoints included progression-free survival (PFS) and safety. Fifty-six of the 63 patients (89%) were found to express the MYD88^L265P mutation and 21 patients (34%) had the CXCR4^WHIM mutation. These mutations promote the growth and survival of WM cells and have emerged as new targets for the treatment of patients with WM.

After a median treatment duration of 19.1 months (range 0.5-29.7), IMBRUVICA was associated with a 91% ORR. Estimated PFS and OS rates at 24 months (secondary endpoints) were 69% (95% CI, 53.2-80.5%) and 95.2% (95% CI, 86.0-98.4), respectively. Notably, IMBRUVICA was also associated with a rapid onset of response, with a median time to response of four weeks. Investigator-determined responses were impacted by the MYD88 and CXCR4 mutations; patients carrying MYD88^L265P and CXCR4^WT achieved the highest responses, with a 100% ORR and 91% major response rate. Overall, IMBRUVICA was well tolerated and there were no unexpected toxicities. At the time of analysis, 43 patients (68%) remained on therapy.

"The strength of these results are compelling, as they reinforce earlier data on which IMBRUVICA was approved for Waldenstrom's macroglobulinemia and show even greater efficacy in difficult-to-treat patients," said Thorsten Graef, M.D., Ph.D., Head of Hematology and Global Medical Safety at Pharmacyclics.

The most common Grade 2-4 adverse events (AEs; occurring in >10% of all patients) associated with IMBRUVICA were neutropenia (22.2%) and thrombocytopenia (14.3%). Grade >3 neutropenia and thrombocytopenia occurred in nine (14.3%) and eight (12.7%) patients, respectively. Of note, IMBRUVICA-related neutropenia and thrombocytopenia were reversible, but required a reduction in dose and/or discontinuation of treatment with IMBRVUICA in three of the four patients who developed these conditions. Grade >2 bleeding events occurred in four patients and there were few infections potentially attributed to IMBRUVICA. Atrial fibrillation (AFib) related to IMBRUVICA occurred in three patients, all of whom had a prior history of paroxysmal AFib. AFib resolved when IMBRUVICA was withheld and all three patients were able to continue on therapy per protocol without further event.

Treatment discontinuation remained low (31%) and was consistent with the rates observed in the earlier analysis.