Scottish Medicines Consortium Accepts Imbruvica® (ibrutinib) for Adult Patients with Waldenström's macroglobulinaemia

Scottish Medicines Consortium Accepts Imbruvica^® (ibrutinib) for Adult Patients with Waldenström's macroglobulinaemia

Today’s advice is based on a phase II study in previously treated patients with Waldenström's macroglobulinaemia (WM) which concluded that ibrutinib was associated with an overall response rate of 87–90 percent[1]

High Wycombe, 13 December 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson welcomes the Scottish Medicines Consortium’s (SMC) decision to accept Imbruvica^® (ibrutinib) for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy.¹ Ibrutinib has already been accepted for use in NHS Scotland for the treatment of WM in combination with rituximab in patients who have received at least one prior therapy.[2]

Around 400 people in the UK are diagnosed each year with WM, a rare and incurable blood cancer which damages the B-cells (a type of white blood cell).^[3] There is a high unmet need for effective, convenient and well-tolerated treatment options for previously treated patients with WM.¹ Ibrutinib was the first treatment to be licensed specifically for WM in the UK.[4]

“Today’s advice from the SMC means that patients in Scotland with WM can now access an effective treatment option which has the potential to offer durable disease control, with minimal side effects. Additionally, as ibrutinib is an oral treatment which can be taken at home, patients can avoid the frequent hospital visits required for rituximab administration, relieving some of the burden of this disease and its treatment on patients and their families,” commented Amanda Cunnington, Director of Health Economics, Market Access, Reimbursement and Health Affairs, Janssen UK.

She continued, “We are proud that we have achieved today’s outcome for WM patients in Scotland and pleased with the pragmatic and efficient way that the SMC has assessed ibrutinib for this patient population. At Janssen, we remain committed to furthering innovation and science for the benefit of blood cancer patients across the UK.”

The SMC advice for ibrutinib was based on evidence from one open-label, single-arm, phase II study (1118E).¹ The primary study outcome was the overall response rate (ORR) and the secondary outcome was major response rate (defined as ≥50 percent reduction in serum IgM levels).¹ Other secondary outcomes included time to response, progression-free survival (PFS), overall survival and sustained (for ≥ 8 weeks) haemoglobin improvement.¹ High responses rates with an ORR were achieved by 87 percent of patients at the primary analysis and 90 percent of patients at the final analysis.¹ No patients achieved a complete response but the major response rate was 70 percent and 79 percent at the respective time-points. At the final analysis, median PFS and overall survival had not been reached. Five year, Kaplan-Meier estimates were 54 percent for PFS and 87 percent for overall survival.¹

In the 1118E study, a treatment-emergent adverse event (AE) was reported by 100 percent (63/63) of ibrutinib treated patients and these were considered treatment-related in 67 percent.¹ A grade 3 or higher AE was reported by 29 percent of patients and a serious AE by 38 percent. 11 percent of patients required a dose reduction due to treatment-emergent AEs and 9.5 percent discontinued therapy due to an AE. ¹ The most frequently reported treatment-emergent AEs on the 1118E study of any grade were diarrhoea (37 percent), neutropenia (25 percent), nausea, fatigue, and muscle spasms (21 percent each), epistaxis, sinusitis and upper respiratory tract infection (19 percent each), thrombocytopenia (18 percent) and anaemia (16 percent).¹

The advice from the SMC applies only in the context of an approved NHS Scotland Patient Access Scheme (PAS) arrangement. NICE currently recommends ibrutinib for use within the Cancer Drugs Fund for treating WM in adults who have had at least one prior therapy.[5]

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About ibrutinib

Ibrutinib is licensed in the UK as:[6]

• a single agent for the treatment of 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, and in combination with rituximab for the treatment of adult patients.
• a single agent for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
• a single agent or in combination with rituximab or obinutuzumab the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).
• 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.

Important safety information

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib, please refer to the full  Summary of Product Characteristics for full prescribing information and safety information for ibrutinib.

About Waldenström's macroglobulinemia

Waldenström's macroglobulinemia (WM) is a rare form of non-Hodgkin’s lymphoma (NHL).[7] It causes overproduction of a protein called monoclonal immunoglobulin M (IgM) antibody, which causes a thickening of the blood.³ Around 400 people in the UK are diagnosed each year with WM.³ The causes of WM are unknown, with it typically affecting older adults and being more common in men than women.³

About the 1118E study[8]

The 1118E study is open-label, single-arm, phase II study of 63 symptomatic patients with median prior therapies of two (range, one to nine therapies), of whom 40 percent were refractory to their previous therapy, received ibrutinib at 420 mg/d. Dose reduction was permitted for toxicity.

In the final analysis from the study published in the Journal of Clinical Oncology, the median follow-up was 59 months, and overall and major response rates were 90.5 percent and 79.4 percent, respectively. At best response, median serum immunoglobulin M declined from 3,520 to 821 mg/dL, bone marrow disease involvement declined from 60 percent to 20 percent, and haemoglobin rose from 10.3 to 14.2 g/dL (P<.001 for all comparisons). The median 5-year progression-free survival (PFS) rate for all patients was not reached and was 70 percent and 38 percent for those with MYD88MutCXCR4WT and MYD88MutCXCR4Mut WM, respectively (P=.02). In patients with MYD88WT, the median PFS was 0.4 years (P<.01 for three-way comparisons). The 5-year overall survival rate for all patients was 87 percent.

Grade ≥ 3 adverse events in more than one patient at least possibly related included neutropenia (15.9 percent), thrombocytopenia (11.1 percent), and pneumonia (3.2 percent). Eight patients (12.7 percent) experienced atrial arrhythmia, and seven of the eight continued therapy with medical management.

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Janssen-Cilag Limited is a Janssen Pharmaceutical Company of Johnson & Johnson. Learn more at www.janssen.com/uk. Follow us at www.twitter.com/JanssenUK.

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding 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 materialise, actual results could vary materially from the

expectations and projections of Janssen Pharmaceutica NV and/or 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 behaviour 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 3, 2021, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, 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 nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

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References:

[1] Scottish Medicines Consortium. Advice on new medicines: ibrutinib 140mg, 280mg and 420mg film-coated tablets (Imbruvica®). SMC2387.

[2] Scottish Medicines Consortium. Ibrutinib (Imbruvica) in combination with rituximab for the treatment of adult patients with Waldenström's macroglobulinaemia (SMC2259). Available at https://www.scottishmedicines.org.uk/medicines-advice/ibrutinib-imbruvica-full-smc2259/. Last accessed December 2021.

[3] Lymphoma Action. Lymphoplasmacytic lymphoma and Waldenström’s macroglobulinaemia. Available at https://lymphoma-action.org.uk/types-lymphoma-non-hodgkin-lymphoma/lymphoplasmacytic-lymphoma-and-waldenstroms-macroglobulinaemia. Last accessed December 2021.

[4] WMUK. Ibrutinib now available in Scotland for Waldenstrom’s macroglobulinaemia (WM) patients (with certain restrictions). Available at https://wmuk.org.uk/news/ibrutinib-now-available-scotland-waldenstroms-macroglobulinaemia-wm-patients/. Last accessed December 2021.

[5] NICE. Final Appraisal Determination. Ibrutinib for treating Waldenstrom’s macroglobulinaemia. Available at https://www.nice.org.uk/guidance/ta491/documents/final-appraisal-determination-document. Last accessed December 2021.

[6] Imbruvica 140mg film coated tablets. Summary of Product Characteristics. Available at https://www.medicines.org.uk/emc/product/10025/smpc. Last accessed December 2021.

[7] Macmillan Cancer Support UK. Waldenström’s macroglobulinemia. Available at https://www.macmillan.org.uk/information-and-support/lymphoma/lymphoma-non-hodgkin/understanding-cancer/types-of-non-hodgkin-lymphoma/waldenstroms-macroglobulinaemia.html. Last accessed December 2021.

[8] Treon SP, Meid K, Gustine J, Yang G, Xu L, Liu X, et al. Long-Term Follow-Up of Ibrutinib Monotherapy in Symptomatic, Previously Treated Patients With Waldenström Macroglobulinemia. Journal of Clinical Oncology. 2021;39(6):565-75.

Date of preparation: December 2021

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