Ibrutinib on a Fast Tract for FDA Approval for 17p Deleted Patients

EXTRA! EXTRA!

April 8, 2013 it was announced that the FDA granted breakthrough therapy designation for ibrutinib (Janssen and Pharmacyclics) as a monotherapy for patients with CLL/SLL (chronic lymphocytic leukemia or small lymphocytic lymphoma) with deletion of the short arm of chromosome 17. This genetic mutation is associated with poor prognosis and is one of the worst prognostic factors in patients with CLL. This is what I have.

This is the third breakthrough designation the FDA granted for ibrutinib an investigational Bruton’s tyrosine kinase inhibitor. One was as a monotherapy for previously treated patients with relapsed or refractory mantle cell lymphoma, and the other was as a monotherapy for patients with Waldenström’s macroglobulinemia.

The breakthrough therapy designation was created in 2012. It enables the development and review of drugs shown in preclinical studies to offer potentially substantial improvements over existing therapies for patients with serious or life-threatening diseases to be expedited.

Patients like me with 17p deletion generally do not respond well to chemoimmunotherapy, and are limited on their treatment options. In my case, because I am bi-racial, I have less than a 1% chance of finding a bone marrow donor match. Ibrutinib has the potential to improve the outcome in this serious and life-threatening disease, and is much less risky than a bone marrow transplant.

A Phase II global study of ibrutinib in patients with CLL deletion 17p, will be available this year and Pharmacyclics plans to enroll 111 patients worldwide. The study called “RESONATE™ -17” is a single-arm, open-label, multi-center trial using ibrutinib as a monotherapy in previously-treated patients who have deletion 17p, who did not respond or who relapsed (a high unmet need population). The purpose of the study will be to determine overall response rate.

Those of you following my blog know that I have just completed my 9-month milestone as “a little white laboratory mouse” in the clinical trial with ibrutinib. Dr. Adrian Wiestner, M.D., PhD, of the National Institutes of Health is the lead investigator in the clinical study. Dr. Wiestner just presented the findings from this clinical trial at the American Association for Cancer Research (AACR) in Washington, D.C. Here is an excerpt from Pharmacyclics’ press release from April 8, 2013. Please note that this is a fast track to FDA approval, and applies to 17p deleted CLL/SLL patients like me. :-)

Phase II Ibrutinib Monotherapy Study Shows CLL Patients Achieved Rapid and Sustainable Disease Control Irrespective of Age or High Risk Prognostic Factor

SUNNYVALE, Calif., April 8, 2013 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq: PCYC) today announced results from a Phase II trial of the investigational oral agent ibrutinib which demonstrated rapid and sustained disease control as a monotherapy in untreated, relapsed and refractory chronic lymphocytic leukemia (CLL) patients, irrespective of characteristics that predict poor outcomes to chemoimmunotherapy.

This study was discussed at today's American Association for Cancer Research (AACR) annual meeting in Washington, DC together in addition to 8 other presentations covering advances in clinical and pre-clinical research with ibrutinib. The Phase II study, which was sponsored by the National Heart, Lung and Blood Institute, included an analysis of two CLL patient cohorts: the elderly, above 65 years of age, (n=24, of which 8 were treatment naive) and the high risk genetic group with a deletion of chromosome 17p (del 17p) (n=29, of which 15 were treatment naive). Many elderly patients with CLL are unable to tolerate aggressive therapies. Patients with deletion of chromosome 17p typically are poor responders to chemoimmunotherapy and have limited treatment options with no standard of care defined. Of all CLL patients enrolled in this trial, 72% had been characterized as Rai stage 3-4, indicating an advance stage, high-risk patient population.

The results of the study were presented by lead investigator Adrian Wiestner, M.D., PhD, Hematology Branch, NHLBI, National Institutes of Health. "Ibrutinib was highly efficacious as a single agent in patients with untreated, relapsed and unresponsive CLL, irrespective of their del 17p status," Dr. Wiestner said. "Responses in this study appear to be durable, and results indicate the drug is effective against the disease in lymph nodes, spleen and bone marrow. This is important because existing therapies often fail to effectively eliminate cancer cells in these tissue sites. Targeted therapy for CLL is becoming a reality, and this new approach may greatly improve the lives of patients with this disease."

The study also evaluated in vivo effects of ibrutinib using blood and tissue samples collected before and during treatment. Ibrutinib demonstrated rapid and sustained disease control in blood, lymph nodes, spleen and bone marrow. After 6 months, 95 percent of patients experienced a reduction in lymph node size and all showed reduction in spleen enlargement, with a median reduction of 55 percent. In 26 patients, for whom a bone marrow biopsy was done, tumor infiltration decreased by 82 percent.

The Progression Free Survival probability for these patients at 12 months was estimated to be 94 percent. Most adverse events were mild and manageable and included diarrhea, fatigue and rash, severe events occurred in less than 13 percent of patients. 

"We are very pleased with the continued research that is being demonstrated at AACR across 9 different presentations. These advances show the potential breadth of the ibrutinib program and provide further opportunities for us to pursue. We are grateful for the continued support of our collaborators, investigators, patients and shareholders," said Bob Duggan, CEO and chairman of the board.

Ibrutinib has been designated as a FDA Breakthrough Therapy in CLL patients with deletion 17p, based on data from completed Phase I/II clinical studies, where ibrutinib as a monotherapy was used to treat patients with this disease. Ibrutinib has the potential to improve the outcome in this serious and life-threatening disease, and may provide a substantial improvement over existing therapies for this indication.