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 in four franchises: Neurology and Immunology, Oncology, Fertility, and General Medicine & Endocrinology. Our R&D pipeline positions us with a clear focus on becoming a global specialty innovator in oncology, immuno-oncology, neurology, and immunology.
In 2020, Healthcare generated 38% of Group sales and 40% of EBITDA pre (excluding Corporate and Other). Europe and North America generated 55% of Healthcare’s net sales in 2020. In recent years, we have steadily expanded our presence in growth markets. In 2020, Asia-Pacific and Latin America accounted for 38% of sales.
Neurology & Immunology*
Mavenclad® (cladribine tablets) is now approved in more than 80 countries worldwide, including those of the European Union, United States, Australia, Canada, and Switzerland. We view Mavenclad® as a complementary oral treatment option in our MS product portfolio. Rebif® (interferon beta-1a), a disease-modifying drug used to treat relapsing forms of MS (RMS), is and remains a well-established therapy. Rebif® has been a standard treatment in RMS for more than 20 years, and has more than 1.6 million patient-years of therapy since approval. Following the European Union approval of the Rebif® label update last year, making it a treatment option for RMS that may be continued into pregnancy if clinically needed and while breastfeeding, the U.S. Food and Drug Administration (FDA) followed in May of this year by approving the inclusion of new safety data on pregnancy and breastfeeding in the prescribing information for Rebif® in the United States. This is an important update for women living with MS who wish to start or expand their family, not having to choose between treating their disease or becoming pregnant.
Rebif® has also played an important role in our company support to fight the Covid-19 pandemic, which includes in-kind contributions, product donations, resources, and expertise in consortia and partnerships aimed at fighting the pandemic. As part of the global effort to investigate potential Covid-19 therapeutics and our support of independent research, we worked with the World Health Organization (WHO) and INSERM (the French National Institute of Health) on a donation of up to 300,000 units Rebif® (interferon beta-1a) for their important global Covid-19 clinical trials known as SOLIDARITY and DISCOVERY, respectively. This donation was followed by a collaboration with the US National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH) with a contribution of 3,000 units of Rebif® for the Adaptive Covid-19 Treatment Trial 3 (ACTT 3), which is currently enrolling hospitalized adults with Covid-19 in the United States and in other countries. The NIAID-led study is evaluating treatment with Rebif® in combination with remdesivir, compared with remdesivir alone, in over 1,000 hospitalized adults diagnosed with Covid-19 and will evaluate time to recovery in the combination therapy group relative to the remdesivir-only group.
Generating data around our MS treatments and the risk of respiratory viral infections has been important to help support clinicians as they make treatment decisions for their patients living with MS. At MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting, which took place virtually from September 11 – 13, we presented a total of 54 abstracts across our MS portfolio, including data providing insights on how Mavenclad® and Rebif® do not affect the risk of respiratory viral infections and Covid-19 outcomes in MS patients. We also presented data demonstrating investigational treatment evobrutinib is the first and only Bruton’s tyrosine kinase inhibitor (BTKi) to demonstrate high and sustained efficacy through 108 weeks in clinical studies (for further details see “Research & Development”).
Oncology & Immuno-Oncology*
Erbitux® (cetuximab) is the third best-selling drug in terms of revenue in the portfolio of our Biopharma business and is our flagship product in oncology. 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 wildtype metastatic colorectal cancer (mCRC), as well as both recurrent and/or metastatic and locally advanced squamous cell carcinoma of the head and neck (SCCHN). During the last year, encorafenib in combination with cetuximab has received regulatory approval in several markets worldwide for mCRC BRAF mutant patients. In December, Erbitux® was once again officially included in the China National Drug Reimbursement List (NDRL) for the treatment of RAS wild-type mCRC. This achievement will enable more patients with mCRC in need of innovative targeted therapies to benefit from the use of Erbitux®.
Together with Pfizer Inc., we have made progress in sharing new data, securing additional regulatory approvals and reimbursement decisions with our anti-PD-L1 antibody Bavencio® (avelumab) (for further details see “Research & Development”).
On June 30, the FDA approved Bavencio® for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy, based on the results of JAVELIN Bladder 100. On December 11, 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of Bavencio® as monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic UC who are progression-free following platinum-based chemotherapy. The CHMP’s positive opinion will now be reviewed by the European Commission (EC), with a decision expected in early 2021.
Other highlights from our development pipeline included the advancement of several potential first-in-class/best-in-class compounds. The development program for tepotinib, our oral MET inhibitor designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, has continued to see pivotal clinical, regulatory, and commercial milestones in 2020. Discovered in-house, tepotinib underscores our strategic focus on delivering innovative precision medicines to patients with cancer.
On March 25, tepotinib was approved in Japan for the treatment of patients with unresectable, advanced or recurrent non-small cell lung cancer (NSCLC) with METex14 skipping alterations. The treatment, known as Tepmetko® in Japan, was the first oral MET inhibitor to have received a regulatory approval for NSCLC with MET gene alterations.
On August 25, 2020, the U.S. FDA accepted and granted Priority Review to our New Drug Application for once-daily, orally dosed tepotinib for the treatment of patients with metastatic NSCLC whose tumors have a mutation that leads to mesenchymal-epithelial transition exon 14 (METex14) skipping. Tepotinib was granted Breakthrough Therapy Designation by the FDA in September 2019. On November 26, 2020, the EMA validated our tepotinib application for the treatment of advanced NSCLC with METex14 skipping alterations. On February 3, 2021, we announced that the FDA has approved Tepmetko® (tepotinib) following Priority Review for the treatment of adult patients with metastatic NSCLC harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.
In February 2019, we entered a global strategic alliance with GlaxoSmithKline (GSK) to jointly develop and commercialize the investigational bifunctional fusion protein, bintrafusp alfa (M7824), discovered as a result of our own research. Bintrafusp alfa is a potential first-in-class investigational bifunctional fusion protein designed to simultaneously block two immunosuppressive pathways, TGF-β and PD-L1, within the tumor microenvironment. This bifunctional approach is thought to control tumor growth by potentially restoring and enhancing anti-tumor responses. In preclinical studies, bintrafusp alfa has demonstrated antitumor activity both as monotherapy and in combination with chemotherapy. Based on its mechanism of action, bintrafusp alfa offers a potential targeted approach to addressing the underlying pathophysiology of difficult-to-treat cancers (for further details see “Research & Development”).
In June 2020, the Japanese Ministry of Health, Labour and Welfare (MHLW) granted SAKIGAKE ‘fast-track’ designation for the investigational bifunctional fusion protein bintrafusp alfa, as a potential treatment for patients with BTC. Bintrafusp alfa was previously granted orphan drug designation by both the FDA as well as the EMA in BTC in December 2018. Bintrafusp alfa is being studied in more than 15 different cancers and 11 alliance-led clinical studies, each exploring distinct mechanistic hypotheses related to the action of TGF-β in supporting cancer growth. To date, more than 1,300 patients have been dosed globally in the bintrafusp alfa INTR@PID clinical development program.
Our broad portfolio of small-molecule DNA Damage Response (DDR) inhibitors represents multiple development paths as monotherapies or in combination with immunotherapy, chemotherapy, or radiotherapy (for further details see “Research & Development”).
To date, an estimated 4 million babies have been born with the help of our fertility portfolio. Being the global market leader in fertility drugs and treatments, with a unique and broad portfolio from therapeutics to lab technologies, our Fertility franchise is an important growth driver for our Biopharma business. Infertility represents an increasing challenge globally due to demographic changes and growing lifestyle adjustments like delayed childbearing. In this highly specialized market, we enable treatment individualization including digital health solutions and technologies in assisted reproductive technologies (ART) for patient convenience. With our current portfolio, we are well equipped to be the Fertility partner of choice for our customers and to further improve ART through innovative solutions across therapeutics, lab technologies, services, and digital health solutions.
The Pergoveris® Pen is the first product with a combination of recombinant follicle-stimulating hormone (FSH) and recombinant luteinizing hormone (LH) in a ready-to-use liquid version, eliminating the need for mixing. It thus provides an improved and convenient treatment option for women with severe deficiency of both FSH and LH. Launches around the globe will continue in order to provide patients with access to this therapeutic.
On the occasion of the annual meeting of the European Society of Human Reproduction and Embryology (ESHRE), we launched the Digital Congress Center (DCC). Our DCC provides opportunities to leverage the interaction in a digital way and to reach the customers, especially during pandemic times. Our DCC allows digital means for collaboration, bringing together internal and external expertise.
General Medicine & Endocrinology*
Every day, more than 80 million patients around the world use our trusted general medicine and endocrinology (GM&E) medications. Concor®, Euthyrox®, Glucophage®, and Saizen® are highly valued brands and market leaders in many key markets worldwide. As a result, GM&E is 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 the overall profitability of Healthcare and our company. Although no longer patent-protected, the brand equity of our products, built up over decades, makes them cornerstones for the treatment of chronic cardiovascular, metabolic, and endocrine diseases.
Concor®/Concor Cor®, containing bisoprolol, is the leading beta-blocker worldwide in volume shares for treating hypertension and cardiovascular diseases such as coronary heart diseases and chronic heart failure. In addition to the plain preparations, the Concor® family offers fixed-dose combinations such as Concor Plus®/Lodoz® (bisoprolol with hydrochlorothiazide) and Concor AM® (bisoprolol with amlodipine). Euthyrox®, with the active ingredient levothyroxine, is the worldwide market leader with a market share of 39% in volume 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. During 2020, multiple health authorities worldwide continued to approve Glucophage® in prediabetes when intensive lifestyle changes have failed. This indication for Glucophage® is now registered in 64 countries. Overall, considering the high prevalence of prediabetes and diabetes, we continue seeing great potential for Glucophage®.
We help to raise awareness and education in the areas we operate in, such as thyroid diseases and diabetes. This is well demonstrated by our active role in International Thyroid Awareness Week and our partnership with the International Diabetes Federation (IDF), which serves as a basis for implementation of education and communication activities that emphasize the importance of type 2 diabetes prevention.
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 reach their treatment goals. Since 2019, Aluetta® (the new Saizen® pen) has been rolled out to select markets 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 e-health space, both by building evidence and by leveraging the meaningful use of technology to provide breakthrough solutions for patient engagement, partnership with healthcare practitioners and better payer value proposition.
Further contributions against Covid-19*
Right from the start of the Covid-19 pandemic and all throughout 2020, we have been continuously making every effort to proactively handle the situation and minimize the impact of the pandemic on the supply of our medicines locally and globally through three main levers: the thorough implementation 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. As we continue to navigate the Covid-19 pandemic, we are thinking about the most vulnerable people with chronic diseases such as diabetes and cardiovascular diseases. Through our collaboration with the nonprofit organization Direct Relief, we provided over 8.3 million tablets of Glucophage® (metformin) and Glucovance® (glibenclamide/metformin), 5.5 million tablets of Concor® (bisoprolol) and Concor Plus® (bisoprolol/hydrochlorothiazide), and over 2.7 million tablets to people affected by poverty or emergency situations. Direct Relief has estimated that our donation has helped more than 32,000 patients in crisis areas.
Divestment of the allergy business Allergopharma*
On February 19, 2020, we signed an agreement to sell its allergy business Allergopharma to Dermapharm Beteiligungs GmbH, Grünwald, Germany. The transaction was completed effective March 31, 2020, following regulatory approval and satisfaction of other customary closing conditions. Only the transfer of the business in China, which is to be considered immaterial, was completed on August 31, 2020. Allergopharma is a leading provider of specific immunotherapies for type 1 allergies. In addition to the Allergopharma business in Europe and Asia with its broad portfolio of therapeutic and diagnostic products, the transaction includes the production site in Reinbek near Hamburg. An existing adrenaline autoinjector development project for the treatment of anaphylactic reactions was not part of the transaction and remained with our company.
* The contents of this chapter or section are voluntary and therefore not audited. However, our auditor has read the text critically.