EMA recommends full marketing approval for IMBRUVICA in the European Union

Pharmacyclics, Inc. (NASDAQ: PCYC) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending the granting of full marketing approval for IMBRUVICA^® (ibrutinib) in the European Union.

IMBRUVICA is being jointly developed and commercialized in the United States by Pharmacyclics and Janssen Biotech, Inc. In Europe, once approved, Janssen-Cilag International NV (Janssen) will be the marketing authorization holder. Janssen will market IMBRUVICA in EMEA (Europe, Middle East, Africa), as well as the rest of the world, outside of the United States.

The CHMP recommendation for IMBRUVICA is for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL), or adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, or in first line in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo‑immunotherapy. The positive opinion was based on data from the Phase II study (PCYC-1104) in MCL, and a Phase III RESONATE™ study (PCYC-1112-CA) and a Phase II study (PCYC-1102) in CLL.

The European Medicines Agency is a decentralized agency of the European Union responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the 28 countries of the European Union. The positive opinion of the EMA's CHMP will be reviewed by the European Commission, and a final decision on IMBRUVICA is anticipated later this year. In addition to European markets, a worldwide regulatory filing program for ibrutinib currently is underway.

"We are pleased with the CHMP's positive opinion for a full approval and with their recognition of the statistically significant overall survival and progression-free survival benefits of ibrutinib in CLL, as well as the strength of our MCL data," said Bob Duggan, Chairman & CEO, Pharmacyclics. "Today, we are one big step closer to offering an important, potentially paradigm-changing, new treatment option to patients around the world with these complex and challenging blood cancers."

IMBRUVICA received accelerated approval from the U.S. Food and Drug Administration (FDA) for two indications based on overall response rate: for the treatment of patients with MCL and CLL who have received at least one prior therapy.

The following results are from the CHMP analysis as part of its review of ibrutinib.

MCL Study Efficacy Results
In a multi-center, single-arm, open-label Phase II study (PCYC 1104), the efficacy of ibrutinib in 111 patients with relapsed or refractory MCL were evaluated. A response rate of 68% was observed, with a complete response rate of 21%, and a partial response rate of 47%, with an estimated median follow up of 15.3 months, the estimated median response duration was 17.5 months; the estimated median progression-free survival was 13.9 months.

CLL Study Efficacy Results
RESONATE™ (PCYC-1112) is a Phase III, randomized, multi-center, open-label, international, head-to-head study of single-agent, orally-administered ibrutinib versus the intravenous monoclonal antibody ofatumumab targeting the CD 20 antigen. The study enrolled 391 relapsed or refractory patients with CLL/SLL.

In this study, single-agent ibrutinib demonstrated a statistically significant improvement in progression-free survival (PFS), overall survival (OS), and overall response rate (ORR), regardless of baseline characteristics, as compared with patients treated with ofatumumab.

The median PFS in the ofatumumab arm was 8.1 months and was not reached in the ibrutinib arm because progression events occurred more slowly. The PFS results represent a 78% reduction in the risk of progression or death in patients treated with ibrutinib compared to ofatumumab. The OS median was not reached in either arm, but the results represent a 57% reduction in the risk of death in patients receiving ibrutinib versus those in the ofatumumab arm. Results were consistent across all baseline sub-groups, including those with del 17p.

MCL and CLL Study Safety Results
The most commonly occurring adverse reactions (>20%) were diarrhea, musculoskeletal pain, upper respiratory tract infection, bruising, rash, nausea, pyrexia, neutropenia, and constipation. The most common grade 3/4 reactions (>5%) were anemia, neutropenia, pneumonia, and thrombocytopenia.