– IMBRUVICA ASSOCIATED WITH SIGNIFICANT IMPROVEMENTS IN KEY ENDPOINTS INCLUDING REDUCTION OF THE RISK OF DISEASE PROGRESSION OR DEATH VERSUS TEMSIROLIMUS CHEMOTHERAPY
– PHASE 3 HEAD-TO-HEAD DATA PUBLISHED ONLINE IN THE LANCET AND PRESENTED AT THE AMERICAN SOCIETY OF HEMATOLOGY (ASH) MEETING
– THIS RELEASE CORRESPONDS TO ABSTRACT #469
Today AbbVie (NYSE: ABBV), a global biopharmaceutical company, announced results from the Phase 3 RAY (MCL3001) trial, which showed IMBRUVICA® (ibrutinib) significantly prolonged progression-free survival (PFS; the primary endpoint) and improved overall response rates (ORR; a key secondary endpoint) in patients with relapsed or refractory mantle cell lymphoma (MCL), compared with temsirolimus. Notably, IMBRUVICA was associated with a 57% reduction in the risk of progression or death with a median follow-up of 20 months.
These data were published online in The Lancet today and presented in an oral session at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition in Orlando, FL. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie Company, and Janssen Biotech, Inc.
Mantle cell lymphoma is an aggressive form of blood cancer which arises from B cells, a type of white blood cell (lymphocyte) that originates in the bone marrow.1,2 MCL is more prevalent in men than women.1 The majority of patients are in their mid-60s at diagnosis and the median overall survival rate is three to four years.1,3 “MCL patients typically achieve only short-term remissions with conventional therapies, so the positive results seen with IMBRUVICA in this Phase 3 trial are particularly striking,” said Simon Rule, M.D., Consultant Haematologist, Department of Haematology, and Head of the Lymphoma Service, Derriford Hospital, Plymouth, UK, and RAY study investigator. “As clinicians, we strive to ensure our patients receive safe and effective treatment options. The RAY data show IMBRUVICA was associated with an improved risk-benefit profile compared to temsirolimus.”
IMBRUVICA significantly improved PFS as determined by an Independent Review Committee (IRC) compared to treatment with temsirolimus, resulting in a reduction in the risk of disease progression or death by 57% after a median follow-up of 20 months (HR 0.43 [95% CI, 0.32-0.58; P<0.0001]). The median PFS for IMBRUVICA-treated patients was 14.6 months compared to 6.2 months for patients treated with temsirolimus. IMBRUVICA was associated with a significantly higher ORR versus temsirolimus as assessed by an IRC (72% vs. 40%, respectively; difference 31.5% [95% CI, 20.5–42.5]; p<00001).
Twenty-six patients who received IMBRUVICA (19%) achieved a complete response (CR), while only two patients who received temsirolimus experienced a CR (1%). Of note, the median treatment duration was four times longer in patients taking IMBRUVICA than those receiving temsirolimus (14.4 months vs. 3.0 months, respectively). Median overall survival was not reached with IMBRUVICA, as compared to 21.3 months with temsirolimus (HR, 0.76; [95% CI, 0.53-1.09).
These findings are consistent with results from previous single-arm Phase 2 studies evaluating the safety and efficacy of IMBRUVICA in patients with MCL.
“These data confirm results from an earlier Phase 2 study, which formed the basis of an accelerated approval of IMBRUVICA for MCL patients who have received at least one prior therapy in the U.S.,” said Darrin Beaupre, M.D., Ph.D., Head of Early Development and Immunotherapy at Pharmacyclics. “We are pleased to see these results confirm the benefit of IMBRUVICA for patients with this aggressive form of blood cancer.”
The most common treatment-emergent adverse events (AEs >20%) observed in IMBRUVICA, included diarrhea (29%), cough (22%) and fatigue (22%); AEs observed in temsirolimus, included thrombocytopenia (56%), anemia (43%), diarrhea (31%), fatigue (29%), neutropenia (26%), epistaxis (24%), cough (22%), peripheral edema (22%) nausea (22%), pyrexia (21%) and stomatitis (21%). The most common hematological AEs (>10%) were thrombocytopenia (18% vs. 56%), anemia (18% vs. 43%) and neutropenia (16% vs. 26%).
Overall, 7% of IMBRUVICA patients and 26% of temsirolimus patients discontinued treatment due to AEs. After a median follow-up of 20 months, 42% of IMBRUVICA patients died and 45% of patients who received temsirolimus died.
About the RAY Study
RAY is a Janssen-sponsored Phase 3, open-label trial which enrolled 280 patients with relapsed or refractory MCL who were randomized to receive either IMBRUVICA (N=139) or temsirolimus (N=141).
Patients were given either oral IMBRUVICA 560 mg in accordance with the approved product label or intravenous temsirolimus (175 mg on days 1, 8 and 15 of cycle 1; 75 mg on days 1, 8 and 15 of all subsequent 21-day cycles) until disease progression or unacceptable toxicity. The primary endpoint of the study was IRC-assessed PFS; secondary endpoints included ORR, OS and safety, among others.
IMBRUVICA is currently approved for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients who have del 17p and patients with Waldenstrom’s macroglobulinemia.4 IMBRUVICA is also approved for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.4 Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.4
IMBRUVICA is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK).4 IMBRUVICA was one of the first medicines to receive a U.S. FDA approval after being granted a Breakthrough Therapy Designation, and IMBRUVICA is one of the few therapies to receive three separate designations.
BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.4,5 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.4
IMBRUVICA is being studied alone and in combination with other treatments in several blood cancers. More than 6,100 patients have been treated in clinical trials of IMBRUVICA conducted in 35 countries by more than 800 investigators. Currently, 16 Phase 3 trials have been initiated with IMBRUVICA and 67 trials are registered on www.clinicaltrials.gov.
IMBRUVICA is indicated to treat people with:
- Mantle cell lymphoma (MCL) who have received at least one prior therapy – accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.
- Chronic lymphocytic leukemia (CLL) who have received at least one prior therapy
- Chronic lymphocytic leukemia (CLL) with 17p deletion
- Patients taking IMBRUVICA for CLL or WM should take 420 mg taken orally once daily (or three 140 mg capsules once daily).
- Patients taking IMBRUVICA for MCL should take 560 mg taken orally once daily (or four 140 mg capsules once daily).
- Capsules should be taken orally with a glass of water. Capsules should be taken whole. Do not open, break, split or chew the capsules.