Three-Year Follow-Up Data Showed Patients Achieved Four-Fold Progression-Free Survival Benefit with Single Agent Imbruvica®▼ (ibrutinib) vs Temsirolimus at First Relapse in Mantle Cell Lymphoma

Data presented as an oral presentation at the 14^th International Conference on Malignant Lymphoma (ICML)

BEERSE, Belgium--(BUSINESS WIRE)--Janssen-Cilag International NV (“Janssen”) today announced three-year follow-up data from the Phase 3 RAY study in patients with relapsed or refractory mantle cell lymphoma (MCL). These results demonstrated that the subset of patients treated with IMBRUVICA^®▼ (ibrutinib) at first relapse after one prior line of therapy achieved a median progression-free survival (PFS) of more than two years (25.4 months).¹ This was four-fold longer than treatment with temsirolimus (6.2 months [HR, 0.40; 95% CI, 0.25–0.64]).¹ Data showed median overall survival (OS) with ibrutinib after one prior line of therapy of 3.5 years (42.1 months vs 27.0 months with temsirolimus [HR, 0.74; 95% CI, 0.43–1.30]).¹

Results from the Phase 3, international, randomised, open-label RAY study were presented on June 17, 2017 during an oral session at the 14^th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland. Ibrutinib, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.

In the overall study patient population, which included patients who had received more than one prior line of therapy (median two prior therapies), median PFS was also significantly increased in patients treated with ibrutinib vs temsirolimus (15.6 months vs 6.2 months [HR, 0.45; 95% CI, 0.35-0.60; p< 0.0001]).¹ In addition, ibrutinib tended to increase OS, with a median OS with ibrutinib of 30.3 vs 23.5 months with temsirolimus (HR, 0.74; 95% CI, 0.54-1.02; p=0.0621).¹

“The data from this long-term follow-up further highlight the potential of ibrutinib for patients with mantle cell lymphoma, especially if used at first relapse,” said Simon Rule, M.D., Professor of Clinical Haematology at Plymouth University, Peninsula Schools of Medicine & Dentistry.*

Complete response (CR) was achieved in nearly a quarter (23.0%) of all patients who received ibrutinib.¹ The CR rate in patients who had received one line of therapy prior to ibrutinib (33.3%) was more than double that achieved in patients who had received more than one line of therapy prior to ibrutinib (15.9%).¹ The duration of response in all patients who achieved a CR with ibrutinib was almost three years (35.6 months).¹

The safety profile was consistent with primary analysis and known safety data on ibrutinib. No new safety signals for ibrutinib were observed in the trial. Overall frequencies of adverse events (AEs) were similar or lower in the ibrutinib arm, even with longer treatment exposure.¹ Nearly twice as many patients discontinued temsirolimus due to AEs vs ibrutinib (31.7% vs 17.3%).¹ In addition, exposure adjusted rates of atrial fibrillation were similar between the two groups (0.392 vs 0.331 with ibrutinib and temsirolimus, respectively) and exposure adjusted bleeding rates were lower with ibrutinib vs temsirolimus (2.880 vs 6.683).¹ In the ibrutinib arm, Grade ≥3 AEs included thrombocytopenia, anaemia and neutropenia in 9.4%, 8.6% and 12.9% of patients respectively.¹

MCL is an incurable, aggressive B-cell malignancy with a median OS of three to four years.² Most patients relapse after first-line therapy and have a poor prognosis.^2,3 Despite recent advances and with the exception of a small patient population eligible for allogeneic stem cell transplant, there is no globally recognised standard of care in relapsed MCL.^4,5,6

“We are encouraged by these long-term data which demonstrated the efficacy and safety of ibrutinib after one prior line of therapy in patients with previously treated mantle cell lymphoma. These data add to the growing body of evidence which shows that using ibrutinib earlier in the treatment pathway may have significant benefits for patients,” said Dr Catherine Taylor, Haematology Therapeutic Area Lead, Janssen Europe, Middle East and Africa. “We are committed to addressing critical unmet need in B-cell malignancies such as mantle cell lymphoma which has traditionally had poor outcomes and are aiming to make this a more manageable disease for patients in the future.”

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About the RAY study
The Phase 3, randomised, open-label RAY study compared ibrutinib with temsirolimus in patients with relapsed or refractory mantle cell lymphoma and ≥1 prior rituximab-containing therapy.⁷ Two hundred and eighty patients were randomised 1:1 to oral ibrutinib (560 mg once-daily; n = 139) or intravenous temsirolimus (175 mg: days 1, 8, 15 of cycle 1; 75 mg: days 1, 8, 15 of subsequent cycles; n = 141) until disease progression/unacceptable toxicity. Long-term efficacy was investigator-assessed.⁷

About ibrutinib
Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells.⁸ By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells, thereby delaying progression of the cancer.⁹

Ibrutinib is currently approved in Europe for the following uses:¹⁰

• As a single agent for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL), adult patients with relapsed or refractory mantle cell lymphoma (MCL), or adult patients with Waldenström’s Macroglobulinaemia (WM) who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy.
• As a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy.

Please see the ibrutinib Summary of Product Characteristics for further information.¹⁰

About MCL
Mantle Cell Lymphoma (MCL) is considered a rare disease, characterised by high unmet need and small patient populations impacting fewer than one in 200,000 people in Europe and with a median age at diagnosis of 65.^11,12 MCL predominantly affects more men than women and accounts for five to 10 percent of all non-Hodgkin’s lymphomas.^6,13 MCL typically involves the lymph nodes, but can spread to other tissues, such as the bone marrow, liver, spleen and gastrointestinal tract.¹²

About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com/emea. Follow us on www.twitter.com/janssenEMEA for our latest news.

Cilag GmbH International; Janssen Biotech, Inc.; and Janssen-Cilag International NV are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

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*Disclaimer: Dr. Rule served as an investigator of this clinical study. Dr. Rule does not have a financial interest in the company.

Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding the potential benefits of ibrutinib. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen-Cilag International NV, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2017, including under “Item 1A. Risk Factors,” its most recently filed Quarterly Report on Form 10-Q, including under the caption “Cautionary Note Regarding Forward-Looking Statements,” and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

References
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¹. Rule S, Jurczak W, Jerkeman M, et al. Ibrutinib vs. temsirolimus: three-year follow-up of patients with previously treated mantle cell lymphoma from the phase 3, international, randomized, open-label RAY stidy. Presentation at 14th International Conference on Malignant Lymphoma, Lugano (Switzerland), 14-17 June 2017.
². Herrmann A, Hoster E, Zwingers T, et al. Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol. 2009;27:511-518.
³. Smith A, Crouch S, Lax S, et al. Lymphoma incidence, survival and prevalence 2004-2014: sub-type analyses from the UK's Haematological Malignancy Research Network. Br J Cancer. 2015;112:1575-1584.
⁴. Dreyling M, Geisler C, Hermine O, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl. 3):iii83-iii92.
⁵. Ferrero S, Dreyling M.The current therapeutic scenario for relapsed mantle cell lymphoma. Curr Opin Oncol. 2013;25:452-462.
⁶. McKay P, Leach M, Jackson R, et al. Guidelines for the investigation and management of mantle cell lymphoma. Br J Haematol. 2012;159:405-426
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⁸. O’Brien S, Furman RR, Coutre SE, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15:48-58.
⁹. European Medicines Agency. EPAR summary for the public: Imbruvica (ibrutinib). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/003791/WC500177778.pdf Last accessed June 2017.
¹⁰. Imbruvica Summary of Product Characteristics, March 2017. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003791/WC500177775.pdf Last accessed June 2017.
¹¹. Smedby KE, Hjalgrim H. Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma subtypes. Semin Cancer Biol 2011;21:293-8.
¹². Leukemia and Lymphoma Society. Mantle cell lymphoma facts. Available at: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/lymphoma/pdf/mantlecelllymphoma.pdf Last accessed June 2017.
¹³. Cancer Research UK. Mantle cell lymphoma. Available at: http://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/types/mantle-cell Last accessed June 2017

PHEM/IBR/0617/0002
June 2017