Healthcare discovers, develops, manufactures, and markets innovative pharmaceutical and biological prescription drugs to treat cancer, multiple sclerosis (MS), infertility, growth disorders, and certain cardiovascular and metabolic diseases. Healthcare operates across four therapeutic areas with a clear ambition to become a global specialty innovator: Neurology and Immunology, Oncology, Fertility, and Cardiology Metabolism & Endocrinology. Our R&D pipeline positions us with a clear focus on strengthening our leadership positions in oncology, neurology, and immunology.
Since the start of the Covid-19 pandemic, we have been continuously making every effort to proactively handle the situation and minimize the impact of the pandemic and also of any challenges from the external context on the supply of our medicines locally and globally. To this end, we are using three main levers: the thorough implementation and further development of our business continuity plans across our network, the active management of our stocks, and the assessment of alternative transportation routes to reach our customers and patients.
In 2022, Healthcare generated 35% of Group sales and 33% of EBITDA pre (excluding Corporate and Other). Europe and North America generated 54% of Healthcare’s net sales in 2022. In recent years, we have steadily expanded our presence in growth markets. In 2022, Asia-Pacific and Latin America accounted for 39% of sales.
Erbitux® (cetuximab) is the best-selling drug in terms of revenue in the portfolio of our Biopharma business, is our flagship product in oncology, reaching € 1 billion in sales in 2022. Treating more than 1 million patients since authorization, the product is a standard of care for patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type metastatic colorectal cancer (mCRC), as well as both recurrent and/or metastatic and locally advanced squamous cell carcinoma of the head and neck (SCCHN). We continue to advance our broad lifecycle management strategy, as well, with more than 200 active clinical trials involving Erbitux® including 17 Phase III studies, some of which have registrational purpose.
Together with Pfizer Inc., we have made significant progress in transforming the standard of care globally for patients with locally advanced or metastatic urothelial carcinoma (UC) as we continue to secure additional regulatory approvals and reimbursement decisions for our anti-PD-L1 antibody Bavencio® (avelumab) (for further details see “Research and Development”). As a key growth driver of our Biopharma business, Bavencio® is now approved as a first-line maintenance treatment for advanced UC in 63 countries and has become a standard of care in the treatment of this disease, based on the results of the JAVELIN Bladder 100 trial, the only Phase III study of an immunotherapy to demonstrate a significant overall survival benefit in the first-line setting. In combination with Inlyta, Bavencio® is also approved in the first-line treatment of advanced renal cell carcinoma, and it is considered a standard of care as monotherapy in metastatic Merkel cell carcinoma, a rare form of skin cancer.
We have also continued to expand the availability of Tepmetko® (tepotinib), our oral MET inhibitor designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, with additional regulatory approvals. In February 2022, the European Commission approved Tepmetko® as monotherapy for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymal-epithelial transition factor gene exon METex 14 skipping, who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
With this approval, Tepmetko® became the first and only oral MET inhibitor to be approved in the European Economic Area for treating adult patients with advanced NSCLC harboring alterations leading to METex14 skipping, who require systemic therapy following prior treatment. Tepmetko® is now available in a number of countries globally.
With xevinapant, our potentially first-in-class IAP (Inhibitor of Apoptosis Protein) inhibitor, we are building on our long-standing leadership in the treatment of squamous cell carcinoma of the head and neck (SCCHN). Five-year results from the 96-patient Phase II study presented at the European Society of Medical Oncology (ESMO) Annual Meeting in September 2022 showed that adding xevinapant to chemoradiotherapy (CRT) markedly improved long-term efficacy outcomes in patients with unresected locally advanced SCCHN. This data reinforces the transformative potential of xevinapant over standard of care in the curative setting (for further details see “Research and Development”). We have advanced our global Phase III development program this year, with TrilynX and XRay Vision now recruiting patients.
We made continued progress in our pipeline in 2022, as we advanced the first antibody-drug conjugate (ADC) developed in our labs, the anti-CEACAM5 ADC M9140, into Phase I.
Beyond our ADC platform, our broad portfolio of small-molecule DNA Damage Response (DDR) inhibitors represents multiple development paths as monotherapy or in combination with other DDR inhibitors, immunotherapy, chemotherapy, or radiotherapy.
In 2022, we advanced the development of our potentially best-in-class, potent and selective inhibitor of ataxia telangiectasia and Rad3-related (ATR), M1774. Following completion of the monotherapy dose-escalation part of the DDRiver Solid Tumors 301 study, a monotherapy dose for M1774 has been confirmed for further evaluation in Phase Ib (for further details see “Research and Development”).
On June 3, 2022, we announced that, following an interim analysis of the ongoing global Phase II DDRiver SCLC 250 trial of berzosertib in combination with topotecan in patients with relapsed, platinum-resistant small cell lung cancer (SCLC), we decided to discontinue the study due to low probability of meeting the pre-defined objective of this trial (for further details see “Research and Development”).
To further support our focused research and development efforts in the area of DDR inhibition, in September 2022 we entered a collaboration agreement with licensing option with Nerviano Medical Sciences S.r.l. for the next-generation highly selective and brain-penetrant PARP1 (poly (ADP-ribose) polymerase) inhibitor NMS-293 (for further details see “Research and Development”). The option to license this molecule provides us with the optionality to develop a next-generation PARP inhibitor in combination with our early pipeline of DDR inhibitors and DNA-damaging ADCs.
Neurology & Immunology*
We have a long-standing legacy in neurology and immunology, including more than two decades of experience in multiple sclerosis (MS). We are committed to people living with neuroinflammatory and immune-mediated diseases by focusing on finding solutions addressing unmet medical needs. Our current MS portfolio includes two approved products for the treatment of relapsing MS (RMS) – Rebif® (interferon beta-1a) and Mavenclad® (cladribine tablets). In addition, we are pioneering the therapeutic usage of Bruton’s tyrosine kinase inhibition for MS through the discovery and development of evobrutinib, which targets both inflammatory activity in the central nervous system and immune cells in the periphery to address the underlying causes of ongoing disease progression. Evobrutinib is an investigational highly-selective, oral, CNS-penetrant BTK inhibitor with the potential to become a best-in-class treatment option for people living with RMS. Evobrutinib is in Phase III development for RMS.
Mavenclad® is approved in 88 countries worldwide, including those of the European Union, Switzerland, Australia, Canada, and the United States, for various forms of highly active RMS.
It is a short-course oral therapy for the treatment of adults with various forms of highly active RMS. Rebif®, a disease-modifying drug used to treat RMS, is and remains a well-established therapy. It has been a standard treatment in RMS for more than 20 years and has more than 1.8 million patient-years of therapy since approval.
In addition to our commitment to MS, we also have a pipeline focusing on discovering new therapies that have potential in other neuroinflammatory and immune-mediated diseases, including systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).
Enpatoran, a highly specific potential first-in-class immune modulator blocking the activation of Toll-like receptor (TLR)7 and TLR8, is being developed as a potential new oral therapy for systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). It aims to overcome limitations of available lupus therapies by providing selective inhibition of lupus-relevant disease drivers, which may increase efficacy while preserving immunity against infections. In March 2022, we announced that our first randomized patient was enrolled in our Phase II (WILLOW) study. We remain on track with recruitment of additional patients.
In January 2022, we entered into an out-licensing agreement for sprifermin with TrialSpark/High Line Bio, New York, USA. Sprifermin, a recombinant form of human fibroblast growth factor 18, is currently being investigated in patients with osteoarthritis.
As the global market leader in fertility drugs and treatments, our fertility franchise is an important contributor to our Healthcare business. According to updated data, more than five million babies have been born worldwide with the help of GONAL-f®, a leading therapeutic within our fertility portfolio.
Infertility continues to represent an increasing challenge globally due to demographic changes and ongoing lifestyle adjustments like delayed childbearing. In 2022, our fertility business grew and recorded significant progress across our fertility portfolio from launches to congress presentations and data studies.
Our GONAL-f® 150 IU pen contains the active substance follitropin alfa, a copy of the natural hormone FSH. Treatment with GONAL-f® results in more follicles, oocytes, and embryos than urinary gonadotropins, increasing the chance of pregnancy and live birth. In 2022, GONAL-f® 150 IU pen was further launched in several European and APAC (Asia Pacific) countries, including France, the Baltic countries, Indonesia, Malaysia, and Singapore. Further launches are expected in Europe, APAC, and MEAR (Middle East, Africa, Turkey, Russia, and the Commonwealth of Independent States) regions in 2023, and in Japan in 2024.
Our Pergoveris® pen is the first product with a combination of recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) in a ready-to-use liquid version, eliminating the need for mixing. This makes it a suitable treatment option for women with severe FSH and LH deficiency. In 2022, the Pergoveris® pen was successfully launched in Saudi Arabia and Argentina, among others. It is now available in 51 countries. Launches around the globe will continue in order to provide patients with access to this therapeutic.
Cardiology Metabolism & Endocrinology*
Every day, more than 90 million patients around the world use our trusted Cardiology Metabolism & Endocrinology (CM&E) medications. Concor®, Euthyrox®, Glucophage®, and Saizen® are CM&E brands and contribute to making CM&E the largest business franchise of the Healthcare business sector in terms of sales, with strong growth in all major therapeutic areas of focus, contributing significantly to our overall profitability.
Concor®/Concor Cor®, containing bisoprolol, is a beta-blocker for treating hypertension and cardiovascular diseases such as coronary heart diseases and chronic heart failure. In addition to Concor®/Concor Cor®, the Concor® family offers fixed-dose combinations such as Concor Plus®/Lodoz® (bisoprolol with hydrochlorothiazide).
Euthyrox®, with the active ingredient levothyroxine, is the worldwide market leader for the treatment of hypothyroidism, a disease with high prevalence but still low diagnosis rates in most emerging markets.
Glucophage®, containing the active ingredient metformin, is the drug of choice for first-line treatment of type 2 diabetes available in more than 100 countries. During 2021, multiple health authorities worldwide continued to approve Glucophage® in prediabetes when intensive lifestyle changes have failed. This indication for Glucophage® is now registered in 89 countries. Overall, considering the high prevalence of prediabetes and diabetes, we continue seeing great potential for Glucophage®.
Saizen®, with its active ingredient somatropin, is our main endocrinology product and is indicated for the treatment of growth hormone deficiency in children and adults. Saizen® can be delivered with the Easypod® electromechanical injection device, the only growth hormone injection device able to wirelessly transfer data such as injection times, dates, and doses to the web-based software system Easypod® Connect, making it easier for healthcare practitioners and patients to manage adherence and helping to reach their treatment goals. Aluetta® (the new Saizen® pen) is now available in 28 countries with the objective of expanding the reach of Saizen®, offering additional options for healthcare practitioners and patients and expanding our devices portfolio.
In endocrinology, we differentiate ourselves from competitors through leadership in the eHealth space, both by building evidence and by leveraging the meaningful use of technology to provide new solutions for patient engagement, partnership with healthcare practitioners and better payer value proposition.
* The contents of this chapter or section are voluntary and therefore not audited. However, our auditor has read the text critically.