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: Neurology and Immunology, Oncology, Fertility, and Cardiology Metabolism & Endocrinology with a clear ambition to become a global specialty innovator. 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 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.
In 2021, Healthcare generated 36% of Group sales and 33% of EBITDA pre (excluding Corporate and Other). Europe and North America generated 55% of Healthcare’s net sales in 2021. In recent years, we have steadily expanded our presence in growth markets. In 2021, Asia-Pacific and Latin America accounted for 38% of sales.
Neurology & Immunology*
We have a long-standing legacy in neurology and immunology including more than two decades of experience in Multiple Sclerosis (MS), and 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 have our investigational MS treatment evobrutinib, which is the first Bruton´s tyrosine kinase (BTK) inhibitor to complete Phase III trial enrollment.
In March of this year, French Health Authorities approved Mavenclad® and made it available and reimbursed for people living with MS in France. With this, Mavenclad® is now approved in more than 80 countries worldwide, including those of the European Union, Switzerland, Australia, Canada and the United States. We view Mavenclad® as a complementary oral treatment option in our MS product portfolio. Rebif®, a disease-modifying drug used to treat 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.
Generating data around our MS treatments and the risk of respiratory viral infections has remained important also this year, helping to support clinicians as they make treatment decisions for their patients living with MS. In February, we presented new data from the MAGNIFY-MS study at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021 (for further details see “Research & Development”).
Further data relevant for treatment during Covid-19 were presented at the 2021 American Academy of Neurology (AAN) Annual Meeting in April (for further details see “Research & Development”).
In May, we announced the completion of an out-licensing agreement with MoonLake Immunotherapeutics AG for sonelokimab (M1095) (for further details see “Research & Development”).
We presented a total of 39 abstracts at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in October (for further details see “Research & Development”).
New evobrutinib data were also presented at ECTRIMS, showing that evobrutinib was effective reducing the volume of slowly expanding lesions (SEL), an imaging biomarker of chronic active inflammation and axonal loss within the central nervous system (CNS), making it the first BTK inhibitor to show a significant effect on this biomarker (for further details see “Research & Development”).
In December we announced a strategically focused expansion of our neuroinflammatory pipeline with the acquisition of the rights to develop cladribine for the treatment of generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD).
Erbitux® (cetuximab) is the 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).
Together with Pfizer Inc., we have made progress in sharing new data, obtaining additional regulatory approvals and reimbursement decisions with our anti-PD-L1 antibody Bavencio® (avelumab) (for further details see “Research & Development”).
On January 25, the European Commission approved Bavencio® monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy. This follows the approval of Bavencio® for this indication by the US Food and Drug Administration (FDA) in June 2020. Bavencio® is now approved as a first-line maintenance treatment for advanced UC in 39 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.
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 achieve several milestones in 2021. Discovered in-house at our company, tepotinib underscores our strategic focus on delivering innovative precision medicines to patients with cancer.
On February 3, tepotinib was approved by the US Food and Drug Administration (FDA) with the brand name Tepmetko® (tepotinib) following Priority Review for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. Tepmetko® is the first and only FDA approved MET inhibitor that offers once-daily oral dosing and is administered as two 225 mg tablets (450 mg). This indication was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. In December 2021, Tepmetko became the first and only oral MET inhibitor to receive the Committee for Medicinal Products for Human Use (CHMP) positive opinion in Europe for adult patients with advanced NSCLC harboring alterations leading to METex14 skipping. Tepotinib is available in a number of other countries, and under review by various other regulatory authorities globally.
On September 30, we announced a mutual decision to end the global strategic alliance with GSK to develop bintrafusp alfa, the investigational bifunctional fusion protein designed to simultaneously block TGF-β and PD-L1. This decision was based on the clinical trial data generated to date, including three randomized clinical trials that did not demonstrate a benefit to patients. Based on these findings, several remaining studies in the program were also discontinued, including those in non-small cell lung cancer, triple negative breast cancer, biliary tract cancer, and bladder cancer. Based on the data generated during the agreement, no milestone payments were made by GSK and no future milestone obligations remain (for further details see “Research & Development”).
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 On April 12, we announced initiation of a Phase II trial with registrational intent for berzosertib, the leading asset in our DNA damage response (DDR) inhibitor development program, to further assess berzosertib in combination with topotecan for the treatment of relapsed, platinum-resistant small cell lung cancer (SCLC) (DDRiver SCLC 250). The berzosertib clinical development program is one of the most advanced Ataxia telangiectasia and rad3-related (ATR) inhibitor development programs industry-wide (for further details see “Research & Development”). Berzosertib, formerly known as VX-970, was licensed from Vertex Pharmaceuticals in 2017.
To augment the in-house innovations in our oncology portfolio with potential new solutions for patients with cancer, we entered a worldwide in-licensing agreement with Debiopharm, Lausanne, Switzerland, for the worldwide development and commercialization of xevinapant (Debio 1143), announced in March 2021. Xevinapant, a potent oral antagonist of Inhibitor of Apoptosis Proteins (IAP), is the only medicine in its class in late-stage clinical development and has the potential to be first in class. Xevinapant is currently being investigated in the Phase III TrilynX study for previously untreated high-risk locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), in combination with platinum-based chemotherapy and standard fractionation intensity-modulated radiotherapy. A second global Phase III study will be initiated in the first half of 2022 to evaluate xevinapant in patients with cisplatin-ineligible LA SCCHN.
As the global market leader in fertility drugs and treatments, our fertility franchise is an important growth driver for our Biopharma business. To date, over 4 million babies have been born 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. Despite the challenges we and our customers faced as a result of the Covid-19 pandemic, there was positive progress across our fertility portfolio in 2021 from launches to congress presentations and data studies. Overall, our fertility business has bounced back, making an exceptional contribution to the overall performance of our Healthcare business in 2021.
During the Covid-19 pandemic, we further supported patients with advancing their treatment at home with the release of our Gonal-f® (follitropin alfa) 150 IU pen. In 2021, it was launched in Portugal, Finland and Poland, and we expect the first regulatory approvals in the APAC (Asia Pacific) region soon. A series of studies conducted with fertility patients and nurses highlighted both the ease of use and the patient-friendliness of our Gonal-f® pen.
Our Pergoveris® pen is the first product with a combination of recombinant follicle-stimulating hormone (r-hFSH) and recombinant 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 Q3 2021, the Pergoveris® Pen was successfully launched in India, Mexico and Ecuador and is now available in 44 countries. Launches around the globe will continue in order to provide patients with access to this therapeutic.
Cardiology Metabolism & Endocrinology (CM&E)*
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 highly valued brands and market leaders in many key markets worldwide. As a result, CM&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 our overall profitability. 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 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.