On February 4, 2022 Sanofi reported that Q4 2021 sales growth of 4.1% and business EPS(1) growth of 9.8% at CER (Press release, Sanofi, FEB 4, 2022, View Source [SID1234607749])
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Specialty Care advanced to the largest business unit by sales (€ 3,487 million, +21.3%), driven by Dupixent (+53.1%)
Vaccines -6.5% despite strong Europe sales, reflecting low 2021 U.S. influenza vaccination rates and record shipments in Q3
General Medicines core assets up 2.1%, while GBU sales decreased (-3.8%) mainly due to prioritization and divestitures
CHC continued growth momentum (+5.6%), driven by Cough and Cold, Pain care and Digestive Wellness categories
Full-year 2021 delivered 7.1% sales growth and 15.5% business EPS at CER
Sales grew to €37,761 million driven by Dupixent (€5,249 million, +52.7%) and Vaccines (€6,323 million, +6.8%)
BOI margin reached 28.4% up 1.3 ppts reflecting improvement in gross margin and continued SG&A expense management
Sanofi generated cost savings of €2.410 billion over the period 2020 and 2021, mainly reinvested to drive growth
Business EPS(1) of €6.56, up 11.9% on a reported basis and 15.5% at CER
IFRS EPS of €4.97 (down 49.3%), reflecting capital gain from sales of Regeneron in 2020.
Free Cash Flow(2) reached €8,096 million, doubled over the last three years and exceeding guidance for 2022
Board held on February 3, proposes annual dividend of €3.33, an increase of 4.1%
Progress on Corporate Social Responsibility strategy
Sanofi Health unit and Medtronic Labs to collaborate to expand access to healthcare in low to middle income countries
Strong set of accomplishments across CSR priorities in our 4 Play to Win pillars including the creation of Sanofi Global Health and 2 pre-clinical studies started on assets for pediatric cancers
Key milestone and regulatory achievements on R&D transformation
Dupixent approved in the U.S. for the treatment of moderate-to-severe asthma for children aged 6 to 11 years
Dupixent reported positive pivotal trial results in prurigo nodularis and eosinophilic esophagitis
COVID-19 recombinant booster candidate showed consistently strong immune responses regardless of primary vaccine received
Early stage pipeline significantly strengthened with seven projects entering phase 1 and seven added to phase 2
Agreement to acquire Amunix, an immuno-oncology company, adding pipeline with conditionally activated biologics
Acquisition of Origimm, a biotechnology company specialized in research of skin diseases
2022 financial outlook
Sanofi expects 2022 business EPS(1) to grow low double-digit(3) at CER, barring unforeseen major adverse events. Applying average January 2022 exchange rates, the positive currency impact on 2022 business EPS is estimated to be between +2% to +3%.
Sanofi Chief Executive Officer, Paul Hudson, commented:
"Sanofi has closed 2021 with a strong performance in the fourth quarter driven by high double-digit sales growth of Dupixent, which continues to set impressive record sales quarter after quarter. This quarter marks the first time Specialty Care has led our GBUs by sales, highlighting a significant milestone in our transformation. At the same time, Vaccines delivered another year of record influenza sales and is on a clear growth path as demonstrated at our recent Vaccines Day. In R&D, we continue to be relentless in our commitment to expand our innovative pipeline. Last quarter, Sanofi achieved a new milestone, a first in recent years, by moving seven molecules into Phase 1 and seven pipeline programs into Phase 2 trials, showcasing our success in rapidly advancing potentially transformative medicines. We further strengthened our R&D capabilities with a series of value creating M&A transactions in 2021. Our excellent financial performance validates our ability to increase profitability through improved product mix, supported by expense management and the reinvestment of savings behind our growth drivers, all of which puts us on a trajectory to achieving our 2022 financial targets."
Changes in net sales are expressed at constant exchange rates (CER) unless otherwise indicated (definition in Appendix 9)
(1) In order to facilitate an understanding of operational performance, Sanofi comments on the business net income statement. Business net income is a non-GAAP financial measure (definition in Appendix 9). The consolidated income statement for Q4 2021 is provided in Appendix 3 and a reconciliation of reported IFRS net income to business net income is set forth in Appendix 4; (2) Free cash flow is a non-GAAP financial measure (definition in Appendix 9); (3) 2021 business EPS was €6.56; (4) 2020 IFRS net income reported reflected capital gain from sales of Regeneron shares in Q2 2020)
2021 fourth-quarter and full-year Sanofi sales
Unless otherwise indicated, all percentage changes in sales in this press release are stated at CER1
In the fourth quarter of 2021, Sanofi sales were €9,994 million, up 6.5% on a reported basis. Exchange rate movements had a positive effect of 2.4 percentage points, mainly due to the U.S. dollar. At CER, company sales were up 4.1%.
In 2021 Sanofi sales reached €37,761 million, up 4.8% on a reported basis. Exchange rate movements had a negative effect of 2.3 percentage points. At CER, company sales were up 7.1%.
Global Business Units
Fourth-quarter 2021 net sales by Global Business Unit (variation at CER; € million; % of total sales)
Fourth-quarter 2021 operating income
Fourth-quarter business operating income (BOI) increased 9.9% to €2,256 million. At CER, BOI increased 6.9%. The ratio of BOI to net sales increased 0.7 percentage points to 22.6% (22.5% at CER). In 2021, BOI increased 9.8% to €10,714 million. At CER, BOI increased 13.3%. The ratio of business operating income to net sales increased 1.3 percentage points to 28.4% (28.6% at CER).
Pharmaceuticals
Fourth-quarter 2021 Pharmaceutical sales increased 7.4% to €6,919 million, mainly driven by the Specialty Care portfolio (up 21.3%) with continued strong performance of Dupixent while sales in General Medicines decreased 3.8%. In 2021, Pharmaceuticals sales increased 7.6% to €26,970 million reflecting the strong performance of Specialty Care and General Medicines core assets.
In the fourth quarter, Dupixent (collaboration with Regeneron) sales increased 53.1% to €1,549 million. In the U.S., Dupixent sales of €1,170 million (up 45.8%) were driven by continued strong demand in atopic dermatitis (AD) in adults, adolescents, and children aged 6 to 11 years, and continued uptake in asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Dupixent total prescriptions (TRx) increased 44% (year-over-year) and new-to-brand prescriptions (NBRx) grew 32% despite fewer in-person patient visits to HCP offices, which remain slightly below the pre-COVID level. In Europe, fourth-quarter Dupixent sales grew 60.9% to €187 million reflecting continued growth in AD and additional launches in younger population in AD, asthma and CRSwNP. In Japan, part of the Rest of the world region, sales were €85 million (up 53.4%).
In 2021, Dupixent sales reached €5,249 million, (up 52.7%), of which €3.971 million were generated in the U.S. (up 46.2%). Each of the two regions Europe and the Rest of the World generated approximately 50% of the non-U.S. sales in the period.
In the fourth quarter, Neurology and Immunology sales grew 3.1% to €588 million, reflecting strong Kevzara sales which were partially offset by lower Aubagio sales. In 2021, overall Neurology and Immunology sales remained stable.
Aubagio sales decreased 1.9% in the fourth quarter to €478 million due to lower sales in the U.S. reflecting increased competition partially offset by higher sales in Europe.
Fourth-quarter Kevzara (collaboration with Regeneron) sales increased 48.3% to €91 million due to an increase in global demand for IL-6 receptor blockers and the temporary tocilizumab shortage.
In the fourth quarter, Rare Disease sales increased 9.5% to €818 million driven by Pompe, Gaucher and Fabry franchises performance. In 2021, sales of Rare Disease increased 7.0% reflecting increased patient demand across the portfolio across all three geographic regions. The Pompe franchise reached more than €1 billion of sales in 2021.
Fourth-quarter sales of the Pompe franchise (Myozyme/Lumizyme + Nexviazyme) increased 11.9% to €269 million primarily by new patient accruals across geographic regions. Myozyme/Lumizyme sales increase at 5.5% to €254 million. Sales of Nexviazyme (which was launched in the US and Japan) were €15 million in the fourth quarter (€17 million in 2021).
Sales of the Gaucher franchise (Cerezyme + Cerdelga) increased 12.8% (to €248 million) in the fourth quarter. Over the period, Cerezyme sales increased 13.1% to €181 million, reflecting strong growth in the Rest of the World region. In Europe and the U.S., Cerezyme sales were down 1.6% and 2.3%, respectively while Cerdelga sales were up 11.9% globally driven by switches and new patient accruals in Europe and the U.S.
Fourth-quarter Fabrazyme sales increased 9.0% to €223 million driven by higher demand in Europe and the Rest of the World region and higher inventory in Europe.
Fourth-quarter and full-year 2021 sales of Oncology increased 10.3% (to €240 million) and 16.9%, respectively, driven by the Sarclisa and Libtayo launches which more than offset the impact of Jevtana generic competition in Europe.
Fourth-quarter Jevtana sales decreased 16.8% to €110 million following the entry of generic competition in certain European markets (down 66.0%) at the end of March 2021. In the U.S., sales were up 13.3%, where the Jevtana composition of matter patent has expired in September 2021. However, Sanofi has filed patent infringement suits against generic filers on Jevtana under Hatch-Waxman in the U.S. District Court for the District of Delaware asserting three method of use patents, two of which (US 10,583,110 and US 10, 716,777) expire in October 2030 and the other one (US 8,927,592) expires in April 2031 including 6-month pediatric exclusivities. Sanofi has reached settlement agreements with some of the defendants and the suit against the remaining defendants is ongoing. No trial dates have been scheduled and the remaining defendants have agreed not to launch any generic cabazitaxel product until the earlier of a district court decision in favor of the defendants or four months after the completion of the post-trial briefing. Separately, Jevtana has been granted a data exclusivity on the CARD clinical study results which expires in December 2023.
Fourth-quarter Sarclisa sales were €54 million (versus €25 million in the fourth quarter of 2020) driven by continued launch execution in Europe (€20 million), sales growth in the U.S. (€21 million) and in the Rest of the World region (€13 million) where sales performance was driven by the uptake in Japan.
Libtayo (collaboration with Regeneron) sales were €35 million (up 78.9%) in the fourth quarter driven by increased demand in metastatic cutaneous squamous cell carcinoma (CSCC) as well as additional country launches. Libtayo sales in the U.S. are reported by Regeneron.
In the fourth quarter, Rare Blood Disorders franchise sales decreased 10.4% (€292 million). Excluding industrial sales to Sobi, fourth-quarter sales were up 2.7% mainly driven by Cablivi and Alprolix. Industrial sales (of Eloctate and Alprolix) to Sobi were significantly lower in 2021 than in 2020 due to a change in the supply agreement which resulted in unusually high industrial sales to Sobi in 2020. In 2021 sales of Rare Blood Disorders decreased 3.0% and were up 8.0.% when excluding industrial sales to Sobi.
Eloctate sales were €141 million in the fourth quarter, down 12.2%. Excluding industrial sales to Sobi, Eloctate sales were down 4.4% due to lower U.S. sales (-3.9%) mainly reflecting inventory fluctuation. Sales in the Rest of the World region were down 28.3% reflecting lower industrial sales to Sobi (which are recorded in this region).
Fourth-quarter Alprolix sales were down 16.0% to €113 million. Excluding industrial sales to Sobi, Alprolix sales were up 6.3%. In the U.S. sales were up 5.1%. Sales in the Rest of the World were down 48.1% reflecting lower industrial sales to Sobi (which are recorded in this region).
Cablivi sales increased by 23.3% to €38 million in the fourth quarter driven by launches in Europe (up 50.0% to €19 million). In the U.S., sales of the product were stable at €19 million, with the COVID-19 environment impacting treatment initiations at the hospital level.
General Medicines
Fourth quarter General Medicines sales decreased 3.8% to €3,432 million and 2.3% excluding portfolio streamlining and Praluent U.S. sales. The growth of core assets2 (up 2.1% to €1,429 million and up 3.9% excluding Praluent U.S. sales) was driven by Multaq, Plavix and RezurockTM (consolidated from November 9). The non-core assets sales decreased 7.6% (to €1,783 million) mainly reflecting lower Generics sales and portfolio streamlining (-1.4 ppt impact).
In 2021, General Medicines sales were down 1.4% to €14,218 million and up 0.4% excluding portfolio streamlining and Praluent U.S. sales. In 2021, sales of the core assets were €5,768 million up 5.6% (and up 7.6% excluding Praluent U.S. sales), driven by double-digit growth of Lovenox, Mozobil and Thymoglobulin as well as Toujeo performance. Non-core assets sales were €7,642 million, down 6.2% reflecting portfolio streamlining (-1.8 ppt), as well as lower Lantus, Aprovel/Avapro and Generics sales.
In the fourth quarter, global Diabetes sales decreased 1.5% to €1,091 million, reflected lower sales in Europe (down 4.0%) and the Rest of the World (down 8.8%), partially offset by growth in the U.S. (up 10.4%). In 2021, Diabetes sales were down 0.8% mainly as a result of lower Lantus sales partially offset by growth from Toujeo and Soliqua.
Fourth-quarter Toujeo sales increased 1.8% to €230 million due to growth in the U.S. and Europe, partially offset by lower sales in the Rest of the World reflecting price and inventory adjustment in anticipation of the Volume Based Procurement (VBP) for insulins in China which will be implemented in the first half of 2022.
Sanofi has participated in the VBP tender for basal insulin analogues in China in November and was among the bidding winners in the group A with Lantus/Toujeo and then has secured a significant volumes of its long-acting insulins at the hospital level. In 2022, Sanofi expects that its glargine sales to decrease by around 30% in China, benefiting from high volumes at significantly lower prices. Toujeo/Lantus sales were €459 million in China in 2021.
Lantus sales were €583 million, down 2.9% in the fourth quarter, due to lower sales in Europe and China partially offset by growth in the U.S. In China, sales reflected price and inventory adjustment in anticipation of the insulin VBP.
Fourth-quarter Soliqua sales increased 13.0% to €54 million driven by growth in all three geographic regions. In the Rest of World region, Soliqua sales grew 30.0% supported by new launches.
In the fourth quarter, Cardiovascular and Established Rx Products sales decreased 4.5% to €2,121 million. The performance of certain core assets, including Plavix, Praluent and Multaq and the addition of Rezurock was more than offset by lower sales of Lovenox and Generics as well as the impact of the divestments of non-core products. In 2021, Cardiovascular and Established Rx Products sales were down 1.8% (down 0.7% excluding Praluent U.S. sales) impacted by lower Aprovel/Avapro and generics sales as well as the impact of the divestments which offset strong growth of several core assets.
Fourth-quarter Lovenox sales decreased 7.9% to €335 million, reflected high base of comparison in the fourth quarter of 2020 when WHO guidelines recommending the use of low molecular weight heparins in hospitalized COVID-19 patients came into effect. In addition, supply limitations and biosimilar competition in Europe (down 11.1%) affected the performance.
Plavix sales were up 7.5% in the fourth quarter to €222 million due to higher sales in the Rest of the World region (up 11.4%) driven by China (up 28.1% to €88 million) largely offsetting lower sales in Japan and Europe.
Fourth-quarter Aprovel/Avapro sales were down 6.1% to €112 million.
Fourth-quarter Praluent sales decreased 15.9% to €55 million, reflecting the restructuring of the collaboration with Regeneron effective April 1, 2020. Sanofi has sole responsibility for Praluent outside the U.S. while Regeneron has sole responsibility for Praluent in the U.S. Excluding U.S. sales in the comparable quarter last year, higher Praluent sales (up 35.9%) were driven by strong performance in Europe. In China, Praluent is listed on the NDRL (National Reimbursement Drug List) as of January 2022.
Multaq fourth quarter sales grew 20.3% to €99 million, reflecting strong U.S. sales growth.
Sales of RezurockTM, a recently FDA-approved, first-in-class treatment for chronic graft-versus-host disease (cGVHD) for adult and pediatric patients 12 years and older who have failed at least two prior lines of systemic therapy, were consolidated as of November 9 (through the Kadmon acquisition) and generated €20 million since that date.
Pharmaceuticals business operating income
In the fourth quarter, business operating income (BOI) of Pharmaceuticals increased 16.4% to €2,091 million (up 12.5% at CER). The ratio of BOI to net sales increased by 1.7 percentage points to 30.2% (29.9% at CER), reflecting an improvement of the gross margin ratio. In 2021, business operating income of Pharmaceuticals increased 2.2% to €9,409 million (up 4.9% at CER). The ratio of BOI to net sales decreased by 1.0 percentage points to 34.9% (35.0% at CER) reflecting strong investments behind Dupixent partly offset by an improvement in overall gross margin ratio.
Fourth-quarter Vaccines sales decreased 6.5% to €1,964 million, mainly reflecting lower U.S influenza vaccines sales partially offset by successful Efluelda expansion in Europe and Polio/Pertussis/Hib in the Rest of the World region. In 2021, Vaccines sales increased 6.8% supported by Meningitis, Influenza and PPH vaccines.
In the fourth quarter, Polio/Pertussis/Hib (PPH) vaccines sales increased 7.7% to €543 million driven by Pentaxim in China and Hexaxim in Europe. In the U.S., Pentacel sales decreased due to inventory fluctuation and progressive Vaxelis ramp-up. Vaxelis was launched in the U.S. in June 2021, in-market sales are not consolidated and the profits are shared equally between Sanofi and Merck.
Influenza vaccines sales decreased 12.4% in the fourth quarter, reaching €1,093 million. In the U.S. fourth-quarter sales were down 48.3% reflecting lower influenza vaccination rates when compared to last year, which resulted from the prioritization of COVID-19 booster vaccinations at the pharmacy level, as well as record shipments in the third quarter of 2021. In the U.S, FluzoneHD gained 3.5 points share despite market contracted by 17% in volume (Sources: IQVIA Claims Medical (as of 1/1/22); IQVIA Claims Retail (as of 1/2/22)). In Europe, Influenza vaccines sales increased 51.1% driven by the adoption of a preferential recommendation for Efluelda for people above 60 years old in Germany. In the Rest of the World region, influenza sales increased 22.7%. On a full-year basis, 2021 marked another record year with Influenza vaccines sales up 5.9% to €2,628 million.
Fourth-quarter Meningitis sales decreased 31.2% to €91 million, reflecting a high base of comparison in the U.S. in the fourth quarter of 2020, when sales benefited from catch-up vaccinations.
Booster vaccines sales decreased 1.6% in the fourth quarter to €124 million, due to lower sales in the Rest of the World region partially offset by growth in Europe. Vaccination rates in this segment have not yet returned to pre-COVID levels.
Fourth-quarter Travel and endemic vaccines sales increased 17.1%, reflecting a low base of comparison in the fourth quarter of 2020 due to the pandemic environment.
Vaccines business operating income
In the fourth quarter, business operating income (BOI) decreased 22.3% (down 23.9% at CER) to €653 million compared to the same period of last year. This reflects lower U.S. influenza vaccines sales and higher R&D expenses related to Translate Bio and the mRNA center of excellence. In the fourth quarter, BOI to net sales ratio was 33.2% (versus 40.8% in the fourth quarter of 2020). In 2021, BOI increased 11.7% (up 12.5% at CER) to €2,609 million benefiting from sales performance and efficiency gain as well as the payment from Daiichi Sankyo in the first quarter of 2021. BOI to net sales ratio increased 2.2 percentage points to 41.3% (41.2% at CER). Excluding the payment from Daiichi Sankyo, BOI to net sales ratio was 39.4% in 2021.
In the fourth quarter, Consumer Healthcare (CHC) sales increased 5.6% to €1,111 million driven by growth in the U.S. and Europe. This performance was driven by the Cough and Cold franchise, as well as the Pain Care category which benefited from COVID-19 vaccinations. In 2021 CHC sales increased 4.6% mainly due to the growing sales in Digestive Wellness, Pain Care and Mental Wellness categories which more than offset a weak cough and cold season last winter and the divestments of non-core products (-0.8 ppt impact).
In the U.S., fourth-quarter CHC sales increased 12.6% to €280 million driven by double-digit growth of Allergy, Pain Care, Personal Care and Digestive Wellness categories.
In Europe, fourth-quarter CHC sales increased 7.5% to €345 million mainly reflecting growth of the Cough and Cold and Pain Care franchises which also benefited from COVID-19 vaccinations.
In Rest of World, fourth-quarter CHC sales increased 0.8% to €486 million, supported by Cough and Cold and Digestive Wellness categories, partially offset by lower sales of Allergy, Pain Care and Physical Wellness categories.
CHC business operating income
In the fourth quarter, business operating income (BOI) of CHC decreased 2.0.% (-5.3% at CER) to €298 million. The ratio of BOI to net sales decreased 2.7 percentage point to 26.8% versus the prior year which included a capital gain related to divestments of non-strategic assets. In 2021, BOI of CHC increased 5.9% (up 10.2% at CER) to €1,493 million due to higher sales, a strict control of operational expenses and higher capital gains related to divestments of non-strategic assets. The ratio of BOI to net sales increased 1.3 percentage points to 33.4% (33.8% at CER).
Fourth-quarter sales in the U.S. increased 1.8% to €3,820 million supported by the strong performance of Dupixent and double-digit growth of CHC, Diabetes and Oncology. In 2021, U.S. sales grew 10.3%, mainly reflecting Dupixent and double-digit growth of CHC.
In Europe sales increased 9.8% in the fourth quarter to €2,804 million mainly driven by Dupixent performance as well as strong Vaccines growth. In 2021, European sales increased 6.6% due to the growth of Specialty Care products driven by Dupixent as well as the strong performance of Vaccines.
In Rest of World sales increased 2.3% to €3,370 million in the fourth quarter, reflecting the performance of Dupixent and Vaccines which more than offset lower sales of General medicines. Sales in China increased 5.7% to €558 million mainly as a result of the growth of Dupixent, Plavix and Vaccines. In Japan, fourth-quarter sales increased 0.5% to €404 million driven by Dupixent and Sarclisa which more than offset lower sales of Established products. In Rest of World 2021 sales increased 4.4% mainly supported by growth of Specialty Care products driven by Dupixent as well as Vaccines and CHC.
R&D update at the end of the fourth quarter 2021
Regulatory update
The U.S. Food and Drug Administration (FDA) approved Dupixent as an add-on maintenance treatment of children aged 6 to 11 years with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid-dependent asthma.
The FDA accepted for Priority Review the Biologics License Application (BLA) for olipudase alfa for the proposed indication as an enzyme replacement therapy for long-term treatment of non–central nervous system (CNS) manifestations of acid sphingomyelinase deficiency (ASMD) in pediatric and adult patients. The target action date (PDUFA) for the FDA decision is July 3, 2022. Historically known as Niemann-Pick disease (NPD) type A and type B, ASMD is an ultra-rare disorder that affects both children and adults. The estimated prevalence of ASMD is approximately 2,000 patients in the U.S., Europe (EU5 countries) and Japan. Due to the rarity of the disease, many patients go undiagnosed or experience delays before receiving an accurate diagnosis, often while the health complications of ASMD continue to progress. Olipudase alfa has received special designations from regulatory agencies worldwide, recognizing the innovation potential of this investigational therapy. Regulatory submissions for olipudase alfa are currently under review in Japan and the European Union. If approved, it will become the first and only therapy available for the treatment of ASMD.
The FDA accepted for review the supplemental Biologics License Application (sBLA) for Libtayo in combination with chemotherapy, for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC). The target action date (PDUFA) for the FDA decision is September 19, 2022.
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) reaffirmed its opinion that avalglucosidase alfa does not qualify as a new active substance (NAS). Sanofi does not agree with the CHMP’s conclusion on NAS status and is evaluating potential options for avalglucosidase alfa in the European Union.
Portfolio update
Phase 3:
A pivotal trial evaluating Dupixent for the treatment of adults with uncontrolled prurigo nodularis, met its primary and all key secondary endpoints showing that Dupixent significantly reduced itch and skin lesions compared to placebo in this investigational setting. The impact of uncontrolled prurigo nodularis on quality of life is one of the highest among inflammatory skin diseases with intense and chronic itch.
Results from a second phase 3 trial assessing the investigational use of Dupixent in patients 12 years and older with eosinophilic esophagitis (EoE) demonstrated that the trial met its co-primary endpoints in patients taking Dupixent 300 mg weekly, showing significant improvements in clinical and histologic disease measures compared to placebo.
The study conducted by the German-Speaking Myeloma Multicenter Group (GMMG) in patients with newly diagnosed multiple myeloma (MM) and treated with Sarclisa in combination with lenalidomide, bortezomib and dexamethasone (RVd), met the primary endpoint, the rate of minimal residual disease (MRD) negativity after induction therapy and before transplant. This trial is the first Phase 3 study to meet primary endpoint of minimal residual disease negativity in transplant-eligible patients with newly diagnosed multiple myeloma. The trial is ongoing, following the second randomization to evaluate progression free survival (PFS) for Sarclisa and lenalidomide combination as maintenance therapy.
Positive data from two Phase 3 studies (ATLAS-A/B and ATLAS-INH) evaluating the efficacy and safety of fitusiran, an investigational small interference RNA (siRNA) therapy for the prophylactic treatment of adults and adolescents with hemophilia A or B, with or without inhibitors, were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Across both clinical studies, prophylactic treatment with fitusiran reduced annualized bleeding rates by >89% compared to the control arms, showing a statistically significant and clinically meaningful improvement in bleeds when compared to on-demand treatments, and also showing significant improvement in quality of life. The Phase 3 clinical program is ongoing evaluating the efficacy and safety of fitusiran under an amended protocol which includes lower doses and an extended dosing regimen in all ongoing adult and adolescent studies.
Tolebrutinib, the investigational brain-penetrant oral Bruton’s tyrosine kinase (BTK) inhibitor, demonstrated favorable one-year tolerability, after 48 weeks of treatment, in a phase 2b long-term extension study in patients with relapsing forms of multiple sclerosis (RMS). Data were presented at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
A new pivotal study evaluating the efficacy and safety of tolebrutinib, for the treatment of Myasthenia Gravis (MG), enrolled its first patient. The multicenter, randomized, double blind, placebo-controlled, Phase 3 study evaluates tolebrutinib compared with placebo in 154 adult participants aged 18 to 85 years old with moderate-to-severe MG. The primary endpoint is change in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) score, an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities.
Preliminary results from a clinical trial investigating the safety and immunogenicity of a single booster dose of Sanofi and GSK recombinant adjuvanted COVID-19 vaccine candidate showed consistently strong immune responses regardless of the primary vaccine received. Phase 3 trial continues to accrue number of events needed for analysis: results are expected in Q1, 2022.
New nirsevimab MEDLEY Phase 2/3 data and an encore MELODY Phase 3 presentation were presented at ReSViNET 2021, reinforcing the potential of an investigational single-dose preventative immunization to help protect all infants entering their first respiratory syncytial virus (RSV) season.
Phase 2:
The study assessing tusamitamab ravtansine, an anti-CEACAM5 antibody drug conjugate (ADC), in combination with ramucirumab in patients previously treated for gastric cancer, recruited its first patient.
Three phase 2 non-randomized, open-label, multi-cohort, multi-center studies evaluating SAR444245, a non-alpha IL-2 (formerly known as THOR707) enrolled their first patients. In these studies, SAR444245 is evaluated in combination with other anti-cancer therapies for the treatment of patients with NSCLC or mesothelioma, or with head and neck squamous cell carcinoma and is evaluated with or without other anti-cancer therapies in patients with relapsed or refractory B cell lymphoma. Sanofi plans to recruit more than 500 patients across those three trials.
The study evaluating SAR442720, a SHP2 inhibitor also known as RMC-4630, in combination with sotorasib, a KRAS inhibitor, for the second line or later treatment of patients with KRASG12C mutant NSCLC, enrolled its first patient. The primary endpoint of this open-label study with 46 participants is overall response rate (ORR). It is conducted in collaboration with Revolution Medicines and Amgen.
The double-blind, 2-arm Phase 2 study monitoring rilzabrutinib, a BTK inhibitor, for the treatment of adults with moderate-to-severe atopic dermatitis, enrolled its first patient. The primary endpoint of this study is percent change in Eczema Area and Severity Index (EASI) score. Seventy participants with moderate-to-severe atopic dermatitis who are inadequate responders or intolerant to topical corticosteroids are planned to be included.
The study evaluating SAR441344, an anti-CD40L monoclonal antibody developed in collaboration with Immunext, for the treatment of patients with active systematic lupus erythematosus, enrolled its first patient.
Development of Sarclisa in patients awaiting kidney transplantation has been discontinued
Development of SAR445088, a complement C1s inhibitor, in immune thrombocytopenia (ITP) has been discontinued. A Phase 2 study in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) and a safety and tolerability study in adults with cold agglutinin disease (CAD) continue.
Phase 1:
An anti PD-L1 / IL-15 fusion protein, SAR445710, (formerly known as KD033), entered in the Sanofi Phase 1 pipeline for the treatment of solid tumors, following the closing of the acquisition of Kadmon.
A first in human study to evaluate the safety, pharmacokinetics, pharmacodynamics and anti-leukemic activity in various hematological malignancies of SAR443579, an anti-NKp46/CD123 bispecific monoclonal antibody developed in collaboration with Innate Pharma, enrolled its first patient.
Studies for the following new molecular entities in development for the treatment of immuno-inflammatory indications enrolled their first patients: SAR442970, an anti-TNF/OX40L Nanobody VHH, SAR444336, a pegylated IL-2, SAR443765, an anti-IL-13/TSLP Nanobody VHH and SAR442999 an anti-TNFa/IL-23A Nanobody VHH.
The study with SAR443809, an anti-Factor Bb monoclonal antibody for the treatment of rare renal diseases, recruited its first patient.
Sanofi will be transitioning its rights and obligations related to SAR445136, a zinc finger nuclease gene-edited cell therapy candidate in development by Sangamo and Sanofi for the treatment of sickle cell disease (SCD), back to Sangamo over the first half of 2022.
Development of SAR439459, an anti-TGFb monoclonal antibody for the treatment of advanced solid tumors, has been discontinued.
Development of SAR442085, an anti-CD38 monoclonal antibody Fc engineered, for the treatment of multiple myeloma, has been discontinued.
Acquisitions and major collaborations
On November 9, Sanofi announced the completion of its acquisition of Kadmon Holdings, Inc., further strengthening growth and expansion of the General Medicines portfolio.
On November 18, Sanofi announced an equity investment of $180 million and a new strategic collaboration with Owkin, an artificial intelligence and precision medicine company, willing to optimize clinical trial design and detect predictive biomarkers for diseases and treatment outcomes in core areas such as lung cancer, breast cancer and multiple myeloma.
On December 1, Sanofi announced the acquisition of Origimm Biotechnology GmbH, a biotechnology company specialized in the discovery of virulent skin microbiome components and antigens from bacteria causing skin disease.
On December 21st, Sanofi announced that it has entered into an agreement to acquire Amunix Pharmaceuticals, Inc., an immuno-oncology company, leveraging its proprietary, clinically validated XTEN and innovative universal protease-releasable masking technology platform, Pro-XTENTM, to discover and develop transformative T-cell engagers (TCE) and cytokine therapies for patients with cancer. Amunix’s pipeline, which includes lead candidate AMX-818, a masked HER2-directed TCE, offers a strong strategic fit with Sanofi’s focus on developing potentially transformative cancer therapies in immuno-oncology.
An update of the R&D pipeline at as of December 31, 2021, is available on our website:
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Progress on implementation of the Corporate Social Responsibility strategy that is fully integrated in our Play to Win strategy
Sanofi Global Health and Medtronic Labs to collaborate to expand access to healthcare in Low to Middle Income Countries
Globally, Non-Communicable Diseases (NCDs) are responsible for 41 million yearly deaths, equivalent to 71% of all deaths. Of these, 37% are premature deaths affecting those between the ages of 30 and 69. NCDs disproportionately affect people in low- and middle-income countries, where more than 75% of global NCD deaths, and 85% of premature deaths, occur.
Against this backdrop, Sanofi Global Health is launching a multi-country, multi-year partnership with Medtronic Labs to expand access to healthcare for underserved patients living with diabetes and hypertension. This partnership will leverage digital health and a community-based approach to improve disease awareness, diagnosis, and management of diabetes and hypertension. The first phase will focus on Tanzania and Sierra Leone where it aims to reach more than 75,000 beneficiaries in strong collaboration with health system partners. This partnership aims to build a replicable and sustainable approach to community-focused chronic disease management while contributing to strengthening health systems as they build towards Universal Health Coverage (UHC) and the Sustainable Development Goals (SDGs). Sanofi Global Health has teamed up with Medtronic Labs to address the pressing challenge of non-communicable diseases in LMICs3.
Status on our renewed CSR ambition
In 2020, in the context of defining our renewed CSR ambitions we reviewed and updated our portfolio of initiatives. Numbers shown for 2021 below serve as the baseline to highlight our ongoing progress in the implementation of Sanofi’s CSR strategy.
Affordable access
Sanofi Global Health, a nonprofit unit formed within the company in April 2021, aims to provide 30 of Sanofi’s medicines across a wide range of therapeutic areas to patients in 40 of the lowest income countries. Beyond the products provided, Sanofi Global Health will also focus on integrated programs that ensure optimal care management over time for patients.
Sanofi is also committed to helping 1,000 patients living with rare diseases who have no access to treatments and will donate 100,000 vials of medicine for their treatments each year. This continues Sanofi’s 30-year commitment to patients suffering from rare diseases, such as Fabry, Gaucher or Pompe diseases, for which access to treatment is often limited.
Our third initiative on access is to develop a global access plan for all new products, making them available in selected relevant markets within two years of launch.
Sanofi continues its efforts to fight polio and sleeping sickness, two of its legacy programs that address global health issues.
Sanofi has been involved in the fight against polio from the beginning and continues to play a critical role in the delivery of polio vaccines. It has also committed itself alongside the WHO to eliminate sleeping sickness in humans by 2030.
Part of Sanofi’s R&D ambition is to develop innovative medicines to eliminate cancer deaths in children.
To contribute to better resource conservation, Sanofi plans to remove all pre-formed plastic packaging (blister packs) for its vaccines by 2027. In addition, the company is committed to eco-designing all its new products by 2025. To reduce its greenhouse gas emissions by 55% by 2030, all Sanofi sites will use 100% electricity from renewable sources and the company has set a target of a carbon-neutral car fleet, both by 2030.
ESG ratings
In recognition of Sanofi’ continued CSR strategy implementation, a few of Sanofi’s ESG rankings have been positively updated:
MSCI: A (previously BBB)
Sustainalytics: 22,9 (previously 24,7) as of 10/01/2022
DJSI: 86/100 (previously 84/100)
Covid Update
Sanofi also keeps its commitment to making a strong contribution to current global public health priorities, with the supply of up to half a billion doses of authorized vaccines. Sanofi is the only company leveraging its worldwide manufacturing capacity and expertise for the supply of three different authorized COVID-19 vaccines from BioNTech / Pfizer, Moderna, and Johnson & Johnson. Manufacturing teams on three industrial sites of the company in France, Germany and the U.S. are mobilized, with 100 million doses released by end December 2021.
At the same time, Sanofi continues its efforts in the fight against the COVID-19 pandemic with its adjuvanted recombinant protein candidate vaccine, developed in partnership with GSK. Positive preliminary booster data have shown that neutralizing antibodies increased across all primary vaccines received (mRNA or adenovirus) for all age groups tested, with a good safety and tolerability profile. Phase 3 trial continues to accrue number of events needed for analysis as populations around the world are increasingly exposed to COVID-19 variants; results are expected in Q1 2022. Sanofi intends to file booster data with regulatory authorities following the Phase 3 results.
Fourth-quarter and full-year 2021 financial results
Business Net Income4
In the fourth quarter of 2021, Sanofi generated net sales of €9,994 million, an increase of 6.5% (up 4.1% at CER). In 2021, net sales were €37,761 million up 4.8% (up 7.1% at CER).
Fourth-quarter other revenues increased 18.9% (up 15.5% at CER) to €421 million, including decreased VaxServe sales of non-Sanofi products of €288 million (down -10.4 % at CER). In 2021, other revenues increased 6.5% (up 10.1% at CER) to €1,414 million, including VaxServe sales of non-Sanofi products of €1,078 million (down -2.2 % at CER).
Fourth-quarter Gross Profit increased 10.3% (up 7.5% at CER) to €6,944 million. The gross margin ratio increased 2.4 percentage points to 69.5% versus the fourth quarter of 2020, reflecting strong improvement of the Pharmaceuticals gross margin ratio (which increased from 70.9% to 75.4%) driven by favorable impact of growing weight of Specialty Care and efficiency gains in Industrial Affairs. The Vaccines gross margin ratio decreased to 56.0% from 60.7%, reflecting lower sales of U.S. influenza vaccines and inventory destruction associated to this lower demand. CHC gross margin ratio was 62.5%, down 1.5 percentage points. In 2021, the gross margin ratio increased 1.2 percentage point to 71.3% (71.4% at CER) driven by Specialty Care and efficiency gains in industrial affairs.
Research and Development (R&D) expenses increased 4.6% (up 2.8% at CER) to €1,585 million in the fourth quarter, reflecting increase in priority assets development as well as recent acquisitions partly offset by efficiencies. In 2021, R&D expenses increased 2.9% to €5,692 million and were up 4.3% at CER driven by increased investment behind key assets and additional R&D expenses from recent acquisitions which were partly offset by efficiency and the benefits of terminating diabetes and cardiovascular related projects recorded in 2020.
Fourth-quarter selling general and administrative expenses (SG&A) increased 6.0% to €2,758 million. At CER, SG&A expenses were up 3.9%, reflecting increased commercial investments in Specialty Care growth drivers which were partially offset by continued streamlining of General and Administrative expenses (G&A). In the fourth quarter, the ratio of SG&A to sales decreased 0.1 percentage point to 27.6% compared to the prior year. In 2021, SG&A expenses increased 1.7% to €9,555 million (up 3.7% at CER). In 2021, ratio of SG&A to sales was 0.8 percentage point lower at 25.3% compared to 2020.
Fourth-quarter operating expenses were €4,343 million, an increase of 5.5% and 3.5% at CER. In 2021 operating expenses were €15,247 million, an increase of 2.2% and an increase of 3.9% at CER.
Fourth-quarter other current operating income net of expenses was -€356 million versus -€123 million in the fourth quarter of 2020. Other current operating income net of expenses included an expense of €444 million (versus an expense of €290 million in the fourth quarter of 2020) corresponding to the share of profit to Regeneron of the monoclonal antibodies Alliance, reimbursement of development costs by Regeneron and the reimbursement of commercialization-related expenses incurred by Regeneron. In the fourth quarter, this line also included €61 million of net capital gains related to General medicines and CHC portfolio streamlining compared to €72 million in the same period of 2020. In 2021, other current operating income net of expenses was -€946 million versus -€561 million in 2020 and included €318 million of net capital gains related to portfolio streamlining compared to €211 million in 2020. The full-year 2021 expense associated with the monoclonal antibodies Alliance with Regeneron was €1,429 million, which compared with an expense of €1,001 million in 2020 (see appendix 7 for further details).
The share of profit from associates was €18 million versus €4 million in Q4 2020 and included the share of U.S profit related to VaxelisTM.
Fourth-quarter business operating income4 (BOI) increased 9.9% to €2,256 million. At CER, BOI increased 6.9%. The ratio of BOI to net sales increased 0.7 percentage points to 22.6% mainly reflecting gross margin ratio improvement. In 2021, business operating income was €10,714 million, up 9.8% (up 13.3% at CER). In 2021, €730 million of savings were generated and fully reinvested in growth drivers and key programs in R&D. In 2021 the ratio of business operating income to net sales increased 1.3 percentage points to 28.4% (28.6% at CER).
Net financial expenses were €83 million and €328 million in the fourth quarter and full-year 2021 (versus €93 million and 335 million in the same periods of 2020).
Fourth-quarter and full-year 2021 effective tax rate was 20.5% and 20.9% versus 22% in the prior year. Sanofi expects its effective tax rate to be around 19% in 2022.
Fourth-quarter business net income4 increased 13.3% to €1,730 million and increased 10.2% at CER. The ratio of business net income to net sales increased 1.0 percentage points to 17.3% versus the fourth quarter of 2020. In 2021, business net income increased 11.8% to €8,213 million and increased 15.5% at CER. The ratio of business net income to net sales increased 1.3 percentage points to 21.7% versus 2020.
In the fourth quarter of 2021, business earnings per share4 (EPS) was €1.38, up 13.1% on a reported basis (up 9.8% at CER). The average number of shares outstanding was 1,254.9 million versus 1,255.1 million in fourth quarter 2020. In 2021, business earnings per share8 was €6.56, up 11.9% on a reported basis and up 15.5% at CER. The average number of shares outstanding was 1,252.5 million in 2021 versus 1,253.6 million in 2020.
Reconciliation of IFRS net income reported to business net income (see Appendix 4)
In 2021, the IFRS net income was €6,223 million. The main items excluded from the business net income were:
An amortization charge of €1,580 million related to fair value remeasurement on intangible assets of acquired companies (primarily Genzyme: €509 million, Bioverativ: €320 million, Boehringer Ingelheim CHC business: €195 million and Ablynx: €168 million) and to acquired intangible assets (licenses/products: €96 million). These items have no cash impact on the Company.
An impairment of intangible assets of €192 million mainly related to sutimlimab (termination of ITP) and discontinuation of some vaccines R&D projects.
Restructuring costs and similar items of €820 million related to streamlining initiatives.
A €614 million tax effect arising from the items listed above, mainly comprising €415 million of deferred taxes generated by amortization and impairments of intangible assets and €200 million associated with restructuring costs and similar items (see Appendix 4).
Capital Allocation
In 2021, free cash flow before restructuring, acquisitions and disposals increased by 32.6% to €9,977 million, after net changes in working capital (+€1,475 million) and capital expenditures (-€1,400 million). After acquisitions5 (-€1,488 million of which Kiadis -€326 million, Tidal Therapeutics -€135 million, Owkin -€160 million), proceeds from disposals5 (+€667 million) and payments related to restructuring and similar items (-€1,060 million), free cash flow6 increased 16.0% to €8,096 million. After the acquisition of Translate Bio (-€ 2,397 million), Kymab (-€932 million) and Kadmon (-€1,904 million), the dividend paid by Sanofi (-€4,008 million), net debt increased from €8,790 million at December 31, 2020 to €9,983 million at December 31, 2021 (amount net of €10,098 million cash and cash equivalents