Pharmacyclics, Inc. has completed enrollment target of 350 patients for its phase III study using ibrutinib monotherapy versus ofatumumab in patients with relapsed or refractory chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), (RESONATE). As of today, additional 41 patients were screened and are allowed to participate in this study which has now been officially closed to enrollment.
The primary endpoint of this study is to demonstrate a clinically significant improvement in progression-free survival with ibrutinib when compared to ofatumumab. A pre-defined number of progression events will trigger an interim analysis. We would expect to have a read out from the interim analysis during the 1st quarter 2014. If the treatment effect of ibrutinib in comparison to ofatumumab is deemed statistically favorable by an independent review committee a discussion with the FDA and other health authorities for a potential early filing can take place.
"In addition to our outstanding team, we are grateful to the patients, their treating physicians, and the clinical sites for their participation in our RESONATE study and their strong support of the ibrutinib programme," said Maria Fardis, Chief of Oncology Operations and Alliances at Pharmacyclics.
Pharmacyclics also announced the completion of enrollment of the planned 110 patients in the phase II single-arm study using ibrutinib in patients with mantle cell lymphoma (MCL) who progress after bortezomib therapy and have received at least one prior rituximab-containing chemotherapy regimen, SPARK (MCL2001). This global study is conducted by Janssen Research & Development, LLC, and its primary endpoint is overall response rate, which is scheduled to be evaluated 6 months from the completion of enrollment. Further updates to this study will be provided by Janssen.
As previously announced Pharmacyclics expects to file a New Drug Application (NDA) with the FDA for the use of ibrutinib in patients with relapsed or refractory MCL prior to year-end. In the time before a potential US marketing approval Pharmacyclics will strive to provide early access to ibrutinib under an Early Access Programme (EAP). EAPs are clinical studies and allowed under certain circumstances by the FDA. They are designed to provide a mechanism for access to an investigational drug to treat patients with a serious or immediately life-threatening disease or condition until the time of an anticipated US marketing approval. A multicentre, open-label EAP, conducted by Janssen, will be initiated in the United States with ibrutinib for relapsed or refractory MCL patients.
"The completion of the enrollment of our first phase III study with ibrutinib, ahead of schedule, is an important milestone for our clinical development plan and a real achievement for our company," said Bob Duggan CEO and chairman of Pharmacyclics. "As of today we have initiated five phase III studies together with our partner Janssen and we currently have registered with the US National Institute of Health 28 clinical trials using ibrutinib. Thus far over 1200 patients have been dosed in our studies and we are making excellent progress in the development of this investigational drug, as underscored by the most recent three Breakthrough Therapy Designations we received from the FDA. It is Pharmacyclics' goal to advance science and drug development in the hopes of making a significant difference for the betterment of patients with serious unmet needs, and we are steadily progressing towards that worthy goal."
Ibrutinib was designed to specifically target and selectively inhibit an enzyme called Bruton's tyrosine kinase (BTK). BTK is a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel — regulation of apoptosis, cell adhesion, and cell migration and homing.
The effectiveness of ibrutinib alone or in combination with other treatments is being studied in several B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Waldenström's macroglobulinemia and multiple myeloma. To date 5 Phase III trials have been initiated with ibrutinib and a total of 28 trials are currently registered on www.clinicaltrials.gov. Janssen Biotech, Inc. and Pharmacyclics entered a collaboration and license agreement in December 2011 to co-develop and co-commercialize ibrutinib.
Ofatumumab is manufactured by Glaxo Group Limited and distributed by GlaxoSmithKline.
Bortezomib is marketed and distributed by Millennium Pharmaceuticals, Inc.
Pharmacyclics is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative small-molecule drugs for the treatment of cancer and immune mediated diseases.