Sanofi to appeal after disappointment with NICE’s Final Draft Guidance not recommending isatuximab (SARCLISA ) suggesting this standard-of-care treatment in multiple myeloma is not cost-effective even if it had been offered at no cost

MAT-XU-2401812 v1.0 Date of preparation June 2024 Press Release For medical and trade media only England and Wales Sanofi to appeal after disappointment with NICE’s Final Draft Guidance not recommending isatuximab (SARCLISA ) suggesting this standard-of-care treatment in multiple myeloma is not cost-effective even if it had been offered at no cost • We believe the National Institute for Health and Care Excellence (NICE) would not have considered isatuximab plus pomalidomide and dexamethasone (Isa-Pd) cost-effective even if isatuximab is offered at zero price • This appraisal implies NICE lacks a suitable pricing and reimbursement framework that is appropriate for assessing combination therapies • NICE’s decision means relapsed and refractory multiple myeloma (RRMM) patients requiring fourth line treatment in England and Wales could be facing a geographic health disparity due to where they live in the UK, with eligible patients in Scotland and Northern Ireland being able to access Isa-Pd due to reimbursement1,2 • Cancer patients in England and Wales have fallen behind those in other comparable European countries when it comes to accessing licensed and effective combination therapies3 Reading, UK – 20 June 2024. Sanofi announced today that NICE has issued final draft guidance (FDG) not recommending Isa-Pd, within its marketing authorisation, for treating RRMM in adults who have had lenalidomide and a proteasome inhibitor, and whose disease has progressed on their last treatment. 4 Isa-Pd has become a standard-of-care for eligible patients in England and Wales through its availability on the Cancer Drugs Fund (CDF), with over 1,700 patients registered to have started Isa-Pd treatment in England.5 However, we believe under NICE’s preferred assumptions, Isa-Pd is not cost-effective within the current NICE framework, even if isatuximab is offered at zero price (£0). This is due to inflexibility in the current system which does not enable a fair process for appraising combination medicines. We are extremely disappointed as, should this recommendation become NICE’s final guidance, it will be devastating for future myeloma patients in England and Wales diagnosed following the publication of the final guidance. These patients will not be able to access this important combination therapy at a time in their treatment pathway when innovation and alternative treatment options are most needed. Discussions with NICE failed to result in a positive outcome for Isa-Pd, highlighting the potential issues with the current NICE framework for assessing and funding innovative combination MAT-XU-2401812 v1.0 Date of preparation June 2024 therapies, which is failing to keep up with the pace of innovation. The consequence is recommendations that fail to recognise the full value and benefits of combination therapies to patients. Anju Bhalla Head of Oncology and Haematology, Sanofi "We are facing significant issues with the current NICE framework for assessing and funding innovations including combination therapies. In our view, cancer patients in the UK are being let down by the current reimbursement system which fails to recognise the benefits and full value of combination therapies for patients, carers and families affected. In such a rapidly evolving and complex treatment landscape, we are open to working with NICE, as we believe it is time for urgent change.” Sanofi is committed to maintaining access to Isa-Pd as an important fourth line treatment for RRMM patients in England and Wales who have limited alternatives at this later stage of cancer. We intend to appeal the recommendation and urge all stakeholders (including NICE and NHSE) to come together to identify a solution for this complex appraisal. Isa-Pd will continue to be available to new and existing patients currently on this therapy in England and Wales through the CDF, as appropriate, whilst the appraisal process – including any appeals – is ongoing and until NICE publishes its final guidance. Shelagh McKinlay Director of Research and Advocacy, Myeloma UK “This decision is a huge blow and many patients will rightly feel like the rug has been pulled from under their feet. It sets a precedent, not only for people with myeloma but also for other conditions. Every day counts when you’re living with myeloma because only one thing is certain: myeloma will always come back. This means patients need effective treatment options now.  IsaPd works and has significantly improved people’s quality of life since 2020. We simply should not be here; where a vital and effective treatment option which has been a standard of care for years cannot be approved. The system is not delivering for patients and we need to challenge it. Myeloma UK has been involved in every committee meeting about IsaPd and we believe this decision is disappointing. We will be submitting an appeal, and we won’t rest until IsaPd is available to everyone who needs it, no matter where they live.”  Sanofi is grateful for the strong support from the clinical and patient community so far in this process and remains hopeful a way forward can be found. About isatuximab Isatuximab is a monoclonal antibody that targets a specific epitope on the CD38 receptor on multiple myeloma cells.6 It is designed to work through multiple mechanisms of action including programmed tumour cell death (apoptosis) and immunomodulatory activity.6 CD38 is highly and uniformly expressed on the surface of multiple myeloma cells, making it a target for antibodybased therapeutics such as isatuximab.6 About ICARIA-MM The efficacy and safety of Isa-Pd was evaluated in ICARIA-MM, a multicentre, multinational, randomised, open-label, 2-arm, phase 3 study in patients with relapsed and/or refractory MAT-XU-2401812 v1.0 Date of preparation June 2024 multiple myeloma.6 In this NICE appraisal, we provided data from the final analysis of ICARIAMM for a subgroup of people who had received 3 previous lines of treatment: • Median progression-free survival (PFS) [primary efficacy endpoint] in patients receiving Isa-Pd nearly doubled compared to Pd alone (12.4 months versus 6.5 months).4 The fivemonth improvement in PFS represented a 47.6% reduction in the risk of disease progression or death in patients treated with Isa-Pd, versus Pd alone (HR: 0.536).4 • Median overall survival (OS) was 33.3 months for Isa-Pd compared to 17.7 months in the Pd arm.4 The most common adverse events for Isa-Pd were neutropenia (46.7%), infusion reactions (38.2%), pneumonia (30.9%), upper respiratory tract infection (28.3%), diarrhoea (25.7%) and bronchitis (23.7%).6 Serious adverse reactions occurred in 61.8% of patients receiving Isa-Pd. The most frequent serious adverse reactions were pneumonia (25.7%) and febrile neutropenia (6.6%).6 Permanent discontinuation of treatment because of adverse reactions was reported in 7.2% of patients treated with Isa-Pd.6 About multiple myeloma Multiple myeloma is a progressive, incurable cancer of the blood plasma cells.7 It affects around 24,000 individuals in the UK at any one time. 7 There are an estimated 5,900 new cases of multiple myeloma in the UK every year, equivalent to 16 people being diagnosed each day.7 Treatment options become limited as patients make their way through them, as such ensuring as many options are available at each line of therapy is vitally important.7 Combinations are standard-of-care in multiple myeloma and have driven recent progress. 8 About Sanofi We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and potentially life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the centre of our ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY Contacts Quiterie Mertian, Communications Manager, Specialty Care, Sanofi UK & Ireland +44 (0) 7740 935 217| quiterie.mertian@sanofi.com Simon Butler, Corporate Affairs Lead, Specialty Care, Sanofi UK & Ireland +44 (0)7921 054 943| Simon.Butler@sanofi.com References 1 Scottish Medicines Consortium (SMC). Advice: isatuximab (Sarclisa®) is accepted for restricted use within NHS Scotland. 12 April 2021. Available at: https://www.scottishmedicines.org.uk/medicinesadvice/isatuximab-sarclisa-full-smc2303/ Last accessed: June 2024 2 Northern Ireland Formulary. (2020) Managed Entry Decisions. Available at: https://niformulary.hscni.net/managed-entry/managed-entry-decisions/. Last accessed: June 2024 3 EFPIA. Patients W.A.I.T. Indicator 2020 Survey. April 2021. Available at: https://www.efpia.eu/media/602652/efpia-patient-wait-indicator-final-250521.pdf Last accessed: June 2024 4 National Institute for Health and Care Excellence (NICE). Available at: https://www.nice.org.uk/guidance/gid-ta10979/documents/html-content-4. Last accessed: June 2024 MAT-XU-2401812 v1.0 Date of preparation June 2024 5 Jim Shannon and Andrew Stephenson (2024) Multiple Myeloma: Drugs. UK Parliament: (UIN 15638). Available at: https://questions-statements.parliament.uk/written-questions/detail/2024-02-26/15638 Last accessed: June 2024 6 Electronic Medicines Compendium, SARCLISA 20mg/mL concentrate for solution for infusion. Available at: https://www.medicines.org.uk/emc/product/14817/smpc/print#PHARMACOLOGICAL_PROPS. Last accessed: June 2024 7 Myeloma UK. What is myeloma? Available at: https://www.myeloma.org.uk/understandingmyeloma/what-is-myeloma/. Last accessed: June 2024 8 Myeloma UK. Treatment for relapsed myeloma. Available at: https://www.myeloma.org.uk/understanding-myeloma/treating-myeloma/treatment-for-relapsedmyeloma/. Last accessed: June 2024