Ibrutinib monotherapy shows efficacy in patients with MCL or DLBCL

Pharmacyclics, Inc. (the "Company") (Nasdaq: PCYC) today announced the results of two separate Phase 2 studies suggesting that ibrutinib, an investigational oral Bruton's tyrosine kinase (BTK) inhibitor, showed efficacy when used as a monotherapy in patients with relapsed/refractory mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL). Pharmacyclics sponsored both studies and is jointly developing ibrutinib with Janssen Research & Development, LLC. The data were presented today at the European Hematology Association (EHA) 18^th Annual Congress in Stockholm, Sweden.

The findings presented at EHA for patients with MCL or DLBCL expand on the results reported by investigators last year at the American Society of Hematology Congress in December 2012. Ibrutinib was shown to achieve the following key results among patients with relapsed/refractory MCL:

• An overall response rate (ORR) of 68%, including a complete response (CR) of 21% where all signs of cancer are gone, and a partial response (PR) of 47%.
• The estimated median duration of response (DOR) in all responding patients was 17.5 months. The median progression-free survival (PFS) was 13.9 months, and the median overall survival (OS) has not yet been reached, but is estimated to be 58% at 18 months.
• Treatment-emergent adverse events (AEs) reported in greater than 20% of patients included diarrhea (50%), fatigue (41%), nausea (31%), peripheral edema (28%), dyspnea (27%), constipation (25%), upper respiratory tract infection (23%), vomiting (23%) and decreased appetite (21%) and were consistent with previously reported data. Only 8 patients discontinued due to an AE.

Professor Simon Rule, Consultant Haematologist in the Department of Haematology at the Derriford Hospital in Plymouth, United Kingdom, presented the results of this study at the EHA Congress today. He explained, "To see these results from a single agent among MCL patients is quite significant and very promising. The fact that response rates continued to increase over time, with no new safety signals, is particularly reassuring."

In the second study among relapsed/refractory DLBCL patients, investigators examined whether ibrutinib would be more active in the Activated B-cell-like (ABC) subtype of DLBCL compared to the Germinal Center B-cell-like (GCB) subtype. The ABC subtype of DLBCL is dependent on the B-cell antigen receptor (BCR) pathway, of which BTK is a key element. Ibrutinib selectively inhibits BTK, with the aim of inhibiting malignant B-cell growth and proliferation. Results of this study show that:

• Patients with the ABC subtype showed a preferential response to ibrutinib monotherapy compared to those with the GCB subtype (ORR = 41% vs 5%, respectively,s exact test).
• Median overall survival (OS) was 9.7 months for the ABC subtype, compared to 3.35 months for the GCB subtype.
• Safety data from 70 patients identified no new safety signals. Grade 3 or higher AEs were seen in greater than 3% of patients and included fatigue (9%), hyponatremia (9%), pneumonia (7%), dehydration (4%), and pleural effusion (4%).

"These results indicated that ibrutinib monotherapy was an effective treatment for some study patients who had ABC-subtype DLBCL," noted presenting investigator Sven de Vos, M.D., Ph.D., Associate Professor in the Department of Medicine at the UCLA Medical Center, Los Angeles, U.S.A., who presented the results at the EHA Congress today. "Given that patients with the ABC-subtype of DLBCL are difficult to treat, these results are very promising."