Deliver transformative innovation
Dedicated researchers across the globe contribute to our industry-leading pipeline of therapies for serious diseases. Nearly 23 000 scientists, physicians and business professionals design and develop new treatments, focusing on projects and technologies with the potential to have a significant impact on lives.
In 2019, we delivered new therapies for patients with a variety of illnesses, receiving key approvals for medicines ranging from a gene therapy for a rare neurodegenerative disease to a biologic drug for neovascular (wet) age-related macular degeneration, the leading cause of blindness in industrialized countries. And pivotal study readouts and filings lay the foundation for additional drug launches in 2020.
Our consistent investment in research and development – USD 9.4 billion in 2019 alone – fuels this progress. It is also a key pillar of our strategy to build a leading, focused medicines company powered by advanced therapy platforms and data science. Unsatisfied with incremental advances, we prioritize game-changing technologies, with 90% of treatments in development anticipated to be first in class or first in a specific medical indication. We have the resources and the breadth and depth of expertise to place big bets.
We’re pursuing drug targets that seem intractable and working on difficult-to-treat diseases. Novartis researchers employ emerging technologies – from inside and outside our walls – to make progress, collaborating across disciplines. We’re particularly interested in technologies that can be applied to multiple therapeutic areas, allowing us to leverage our scale.
For example, we’re exploring novel anti-inflammatory compounds that block a cellular danger sensor because they have many potential applications. We recently acquired IFM Tre, a company that is developing some of these compounds, to bolster our own broad portfolio of immunomodulatory medicines. We’re identifying and prioritizing opportunities for these assets across our therapeutic areas.
The latest data and digital technologies aid this decision-making while also helping us accelerate and improve the drug development process. Our research and development teams are at the forefront of a companywide effort to harness advances in machine learning and predictive analytics to transform the way we work. We’re scaling up programs and launching new ones to mine petabytes of data – from images of cells to patient test results from thousands of clinical trials – for insights.
An enterprise data and analytics platform built by Novartis called Nerve Live demonstrates our progress. It includes modules that help teams better manage project resources. They can plan and run more effective clinical trials based on what happened in previous studies. In 2019, we finished rolling out the latest Nerve Live modules and launched two new insights centers where we can monitor trials across the company and predict potential issues, such as delays in recruiting patients before they become a problem.
Advanced therapy platforms
We constantly challenge convention, including by questioning the very definition of a medicine. Most pills and injections contain small molecules or proteins. We’re exploring new ingredients such as genes and therapeutic viruses, fundamentally rethinking the tools in a drug hunter’s arsenal. This work centers around advanced therapy platforms – broadly applicable tools with the potential to become therapeutic staples and game-changers for patients.
Adeno-associated viruses (AAVs) are one such example. They are small, benign viruses that can be used to deliver genes to cells inside the body, and they’re powering a wave of gene therapies, including our new treatment Zolgensma. This novel medicine was approved in 2019 in the US for spinal muscular atrophy (SMA) in patients less than 2 years old who have mutations in both copies of a gene called survival motor neuron 1 (SMN1). Infants with the most severe form of the disease, SMA type 1, rapidly lose the motor neurons responsible for muscle functions such as breathing, swallowing and walking. Scientists at AveXis, a Novartis company, designed Zolgensma to address the genetic root cause of the disease in an attempt to halt disease progression.
Teams at AveXis and the Novartis Institutes for BioMedical Research (NIBR) are developing additional AAV-based gene therapies in neuroscience, including potential treatments for Rett syndrome, a genetic form of amyotrophic lateral sclerosis (ALS), and Friedreich’s ataxia. Our researchers have also applied this technology to eye diseases. An experimental gene therapy designed by NIBR researchers for a rare blinding disease began testing in patients in the spring. This complements our ex-US commercialization rights for Luxturna, a gene therapy originally developed by Spark Therapeutics for a rare blinding disease.
AAVs are particularly useful for delivering genes to cells inside the body. We’re using different tools, however, to deliver and modify genes outside the body to generate cell therapies. Take our chimeric antigen receptor T-cell (CAR-T) programs, which employ lentiviruses. A patient’s T-cells are extracted and reprogrammed to recognize and fight cancer cells before being infused back into the patient, where they become a “living drug.”
We continued to build on the success of our flagship CAR-T therapy, Kymriah, in 2019. It’s now approved in more than 20 countries for certain pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. It’s also approved in these countries for a particular type of relapsed or refractory large B-cell lymphoma in adult patients. Some of the first patients to receive Kymriah have shown no signs of relapse for more than five years.
But not all patients have such a positive outcome. We’re designing new CAR-T therapies and exploring how to combine them to overcome resistance and relapse in a variety of difficult-to-treat cancers. Novartis has a deep CAR-T pipeline. Our focus is to broaden the impact of this advanced therapy platform by going deeper in B-cell malignancies and reaching patients with other hematological cancers and solid tumors.
We’re designing new CAR-T therapies and exploring how to combine them to overcome resistance and relapse in a variety of difficult-to-treat cancers. Novartis has a deep CAR-T pipeline
Teams are also examining ways to improve the manufacturing of these personalized treatments to better serve patients. We’re using a new, innovative manufacturing process, for example, to generate YTB323, an investigational CAR-T therapy that’s being studied in certain blood cancers.
CRISPR is another tool that we’re exploring for cell and gene therapies. It’s a popular method of genome editing that’s used in countless labs around the world. We aim to make medicines with it. For example, we’re working on a potential treatment for sickle cell anemia with CRISPR technology licensed from Intellia Therapeutics.
Our pioneering work with novel technology extends beyond cell and gene therapies. For example, researchers at Advanced Accelerator Applications (AAA) and Endocyte, both Novartis companies, are developing radioligand therapies, targeted drugs that are designed to deliver radiation to tumors. Lutathera – a treatment for gastroenteropancreatic neuroendocrine tumors – received new approvals from health regulators in Canada, Switzerland and Israel in 2019. And an experimental radioligand therapy for metastatic castration-resistant prostate cancer is advancing through late-stage clinical trials.
Our researchers are also exploring a new class of therapeutics called molecular glues. The cellular world is full of compounds that either lock proteins in an inhibited format or bind two protein molecules together. Such “glues” can help cells function and thrive. Inspired by Mother Nature, Novartis scientists are now creating new, synthetic glues to short-circuit disease cells and treat serious illnesses. Four of our experimental glues have already entered clinical testing for the treatment of certain cancers and immunologic and neurodegenerative diseases.
Data science and digital technologies
We’re working to transform the way that we find and test medicines by harnessing the latest data science and digital technologies. There are parallels between this effort and our investment in advanced therapy platforms. In both cases, we’re leveraging our size and expansive disease area research to focus on innovations with relevance beyond a single research project. Our aim is to apply emerging tools at scale to bring treatments to patients faster while reducing costs.
Novartis is a data powerhouse. We’ve collected approximately 2 million patient-years of data through our clinical trials alone. And we’re taking steps to make the most of this strategic asset. In 2019, we expanded and launched major data and digital initiatives while forming new collaborations to augment our growing internal capabilities.
Data42 is a program that’s laying the technical and cultural foundation for a revolution in our organization. The ambition is to change the way that we conduct drug discovery and development in this era of big data. We’re integrating massive amounts of data that previously existed in silos inside and outside the company and taking a holistic look at it. The data ranges from images of cells that have been treated with different chemicals, to blood samples from patients analyzed within clinical trials. We’re using machine learning and artificial intelligence to mine the integrated, anonymized data for connections and patterns that are indiscernible to the human brain. Our data scientists are building models and applications that will empower Novartis teams to ask new questions, make better predictions and save time. We can use the platform to prioritize drug targets, identify development opportunities for compounds, and more.
We’re combining our own data with external data to make progress. Take a collaboration with the University of Oxford’s Big Data Institute, which will draw on data from multiple sources, including Novartis clinical trials as well as UK Biobank, Genomics England and China Kadoorie Biobank. The team will develop new machine learning algorithms to identify patterns across massive datasets in an effort to better understand disease and predict how patients will respond to existing and new medicines, beginning with programs in multiple sclerosis, dermatology and rheumatology.
Novartis researchers aspire to help patients through their work on medicines. Yet interactions with patients haven’t been a major focus of most drug discovery and development programs. That’s changing. We’re systematically employing data and digital tools to make clinical trial participation easier and more worthwhile for patients. We’re also using sensors and cutting-edge technology to measure new clinical endpoints and determine if experimental treatments help patients with symptoms that matter in their daily lives.
Collaborations promise to accelerate this effort. This includes an alliance with Verily, an Alphabet company, and other pharmaceutical companies. Verily has built a platform that fosters the testing of patient-centric, technology-enabled research approaches. Initially, we’re using it to test digital recruitment for clinical trials. Pharmaceutical companies have historically relied on doctors at a limited number of sites to identify participants for clinical trials. We might be able to improve patient participation in research by connecting with them in new ways, including through online health registries.
Mental health is another area of exploration for us. We are finding new ways to measure and address it. Many patients with serious diseases suffer from anxiety and depression, which can exacerbate their underlying conditions. Imagine being able to deliver proven but difficult-to-access interventions such as cognitive behavioral therapy via smartphone. That’s the goal of a collaboration with Pear Therapeutics, which develops software applications to treat disease. We’re working together to design and test a prescription digital therapeutic to treat depressive symptoms in patients with multiple sclerosis, a project with potential applications in other diseases.
As we continue to develop platforms and processes with the potential to scale, we’re changing the way that we approach the development of medicines to take advantage of them. We’ve started to convene agile teams of digital experts to identify and prioritize risks and opportunities for each molecule during development and for clinical care. In 2019, we examined the possibilities for our most promising assets, including CFZ533 (iscalimab), an experimental immunomodulatory therapy with the potential to make kidney and liver transplants durable. And we plan to routinely take this approach in the future.
Advancing transformative therapies
Our investment in CFZ533 illustrates our ability to explore areas that are difficult for other companies to pursue, yet where there is high unmet need for patients. We have the scale and breadth and depth of scientific expertise to explore new frontiers, take smart risks, and attack problems from multiple angles.
Another big bet is TQJ230, a novel molecule designed to alter mRNA, which carries instructions for protein synthesis from DNA. We recently licensed the investigational therapy from Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals. It has the potential to be the first medicine approved to treat patients with elevated levels of lipoprotein(a) and established cardiovascular disease.
In early 2020, we also acquired The Medicines Company, which has developed an investigational cholesterol-lowering therapy called KJX839 (inclisiran). It’s a small-interfering RNA molecule that reimagines the treatment of atherosclerotic heart disease and familial hypercholesterolemia. The Medicines Company submitted a New Drug Application for KJX839 with the US Food and Drug Administration (FDA) in late 2019.
As we pursue such innovative projects, we remain focused on delivering new treatments for patients. In 2019, we launched several medicines in addition to Zolgensma, the novel gene therapy. These treatments have the potential to change the standard of care for devastating diseases. We also shared promising clinical trial results throughout the year.
We received approval in the US for Beovu, a biologic drug designed to treat neovascular (wet) age-related macular degeneration, which affects up to 20 million people worldwide. The standard of care for this common cause of vision loss – which occurs due to abnormal, leaky blood vessels in the retina – involves injections into the eye. Beovu is a VEGF pathway inhibitor.
In March, we launched Mayzent, the first oral drug approved to treat secondary progressive multiple sclerosis (SPMS), an advanced form of the autoimmune disease. It’s a selective sphingosine-1-phosphate receptor modulator. The FDA approved our therapy based on trial results that showed it significantly reduced the risk of disease progression, including impact on physical disability and cognitive processing speed. It represents a breakthrough for patients. We are authorized to market the drug broadly to treat adults with relapsing forms of multiple sclerosis, including SPMS with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.
We continue to search for new solutions for multiple sclerosis and reported strong results for OMB157 (ofatumumab) in patients with relapsing forms of the disease. In two Phase III studies, our experimental therapy – a biologic drug that targets CD20 – significantly reduced the relapse rate in patients compared to a standard treatment, teriflunomide. OMB157, if approved, will potentially become a treatment for a broad relapsing multiple sclerosis population and the first B-cell therapy that is easy to manage in a monthly self-administered injection at home.
Oncology and Hematology
We received approval in the US and other markets for Piqray in a particular form of advanced breast cancer. Piqray offers a more personalized approach to treatment. It is a targeted, small-molecule drug designed to inhibit the effects of a mutation in the gene PIK3CA, the most commonly mutated gene in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. The treatment is approved in combination with fulvestrant for postmenopausal women, and men, with HR+/HER2- advanced or metastatic breast cancer with a PIK3CA mutation. A Phase III trial showed that Piqray plus fulvestrant nearly doubled patients’ median progression-free survival compared to fulvestrant alone.
Our work in hematology covers blood cancers and other blood disorders. In 2019, we advanced a treatment for sickle cell disease, a debilitating inherited genetic blood disorder. We received approval for Adakveo in the US for sickle cell pain crises, which are unpredictable, severe events associated with life-threatening complications. The approval was based on data showing a reduction in the annual rate of pain crises in patients. Adakveo is a biologic agent designed to block P-selectin-mediated multicellular adhesion.