Deliver transformative innovation

Our research and development activities span multiple therapeutic areas and are fueled by creativity and commitment. Novartis employs more than 23 000 scientists, physicians and business professionals focused on finding innovative treatments and bringing them to patients.

In 2018, our dedicated researchers made progress on a number of fronts, especially in neuroscience, oncology and ophthalmology. They also embraced new technology as we expanded data science and digital initiatives while acquiring key assets, such as gene therapies, to bolster our pipeline of unconventional medicines.

Our teams harness new inventions and knowledge to discover and develop transformative therapies. Each treatment begins as an idea, which is incubated, refined and tested – first in the laboratory and later in the clinic – over many years. Our researchers advance promising ideas from a variety of internal and external sources, focusing on projects with the potential to significantly improve or extend lives.

It takes courage and collaboration to produce breakthrough therapies. Our teams seize a challenge, working on intractable diseases and difficult drug targets, or molecules that play a central role in human illness. We place big bets, prioritize our resources, and find or build new tools to make progress where others have failed. We’re deploying genome engineering tools, for example, to design and develop therapies for certain types of cancer as well as several rare genetic diseases. And we’re changing the definition of a medicine in the process.

Conventional pills and injections continue to bring tremendous benefit to patients and society, but new technology platforms such as chimeric antigen receptor T-cell (CAR-T) therapy may offer advantages for certain difficult-to-treat diseases. Our researchers have adopted an open, multidisciplinary mindset to explore the possibilities. We are working on novel types of medicines, such as radioligand therapies and and molecular glues, while collaborating to overcome obstacles and following the science wherever it leads. Project teams tap experts and inventions from across the company and beyond, forging alliances with external innovators at major biomedical research institutions.

Rising prevalence of liver disease

We are pursuing new therapies for nonalcoholic steatohepatitis (NASH), a growing unmet health need. For instance, prevalence in the US is expected to increase by 65% from 2015 to 2030

Our strategy for tackling an increasingly common disease called nonalcoholic steatohepatitis (NASH) also illustrates this collaborative approach. NASH is a bit like multiple diseases in one, typically starting with the buildup of fat in the liver, but also involving inflammation and liver cell death leading to scarring. Given the biological complexity, we’re working to develop combination therapies for NASH straight out of the gate, before there is a single drug approved for the disease. And we’re using molecules born inside and outside of Novartis for this effort.

Teams are also leveraging the latest innovations in data science and digital technologies to streamline the drug discovery and development process. Each step of the complex, lengthy process presents an opportunity for tech-savvy researchers to innovate.

Teams are leveraging the latest innovations in data science and digital technologies to streamline the drug discovery and development process

We are using machine learning, predictive analytics and related tools to improve the way that we find potential medicines at every stage of research. We’re also using these new methods to transform large clinical trials that are designed to determine if therapies are safe and effective.

Data science and digital technologies

Novartis expanded key data science and digital programs in 2018 to accelerate the metamorphosis of research and development. One challenge that we face is finding the time to dream up applications for emerging technologies. To address this hurdle, we encourage employees to pitch projects with transformative potential through programs such as Genesis Labs, an internal incubator for multidisciplinary ideas. Teams – which can include external researchers – are given the time, space, mentors and resources to develop and rapidly test their proposals.

A number of Genesis Labs projects focus on the integration of data science and digital technologies in research and development. One team, for example, is using machine learning – a method in which computers teach themselves from data – to improve how we analyze tissue samples that have been placed on slides, particularly for preclinical safety studies. Our researchers process hundreds of thousands of slides each year. This project could streamline and enhance their work.

In 2018, we expanded Genesis Labs beyond our early research labs, inviting employees in our drug development and manufacturing groups to participate. The program organizers received nearly 250 initial proposals from 22 different Novartis sites and ultimately selected six projects to move forward.

While Genesis Labs emphasizes prototyping, other initiatives aim to increase the use of data science and digital technologies in our daily work. Take Nerve Live, a platform designed to help us run development operations, including clinical trials, faster and more efficiently. Two years ago, we began to consolidate our huge pool of past and present data about our clinical trial operations into one centralized system, working with computational experts to create custom apps that can bring actionable insights at key decision-making points. Nerve Live is the result.

The platform employs predictive analytics to help us select the best trial sites, predict participant enrollment, optimize drug supply, anticipate delays before they occur, and more. It includes a control room that opened in 2018 and receives real-time updates on all ongoing trials to direct actions in support of our global teams. Data is one of our greatest assets, and tools such as Nerve Live will help us unlock its potential.

In addition to helping us behind the scenes, digital technologies are increasingly visible to patients in our clinical trials. We’re leveraging smartphones, electronic health diaries and wearable devices to improve our research as well as the patient experience. In some cases, it’s possible to collect comprehensive data from patients without requiring them to visit clinical trial sites at regular intervals. To this end, we are collaborating with startup companies, such as Science 37, that design decentralized clinical trials, which are more convenient for patients. We have already initiated decentralized clinical trials for cluster headache, acne and NASH.

In some cases, digital technologies are even changing what the word “medicine” means. We are collaborating with Pear Therapeutics, a pioneer in prescription software applications. Such “digital therapeutics” undergo rigorous testing in clinical trials before they’re considered for approval by health authorities. We’re working with Pear Therapeutics to develop mobile apps for patients with schizophrenia and multiple sclerosis and to commercialize an app for substance use disorder. The apps are designed to deliver cognitive behavioral therapy anywhere at any time.

New technology platforms

The rise of digital therapeutics illustrates that medicines increasingly take different forms from conventional pills and injections. In 2018, we made significant investments in several new technology platforms – broadly applicable tools with the potential to become therapeutic staples and game changers for patients.

For example, we acquired Advanced Accelerator Applications (AAA) and its radioligands, targeted drugs that are designed to deliver radiation to tumors. AAA’s treatment for gastroenteropancreatic neuroendocrine tumors, a peptide receptor radionuclide therapy called Lutathera, was the first of its type to receive approval in the US and Europe. Additional radioligand therapies targeting other tumor types are under development. We also acquired Endocyte, a company developing similar technology to treat prostate cancer.

We also advanced our portfolio of cell and gene therapies in 2018. These involve genetically reprogramming cells either outside or inside the body. Our flagship cell therapy, Kymriah, is a CAR-T therapy that is generated by removing a patient’s own white blood cells, reprogramming them to recognize cancer, and then reinserting them into the body. In August 2017, this “living drug” became the first CAR-T therapy approved in the US, providing a much-needed treatment option for pediatric and young adult patients with a particular type of acute lymphoblastic leukemia. In 2018, we received approval in the US, EU and other markets for a second indication: a particular type of relapsed or refractory large B-cell lymphoma in adult patients.

Our teams are designing and developing next-generation CAR-T therapies with the potential to target more than one protein on cells. Researchers are also working to apply CAR-T technology to other tumor types, streamline our manufacturing processes, and further increase manufacturing capacity in an effort to help more patients.

Car-T cell

Within the patient’s body, CAR-T cells have the potential to recognize cancer cells and other cells expressing a specific antigen, and attach to them, which may initiate direct cell death

In addition to growing our CAR-T pipeline, we’re investing in a platform that facilitates the genetic reprogramming of cells inside the body. In 2018, we closed deals with biotech companies that have deep experience with adeno-associated viruses (AAVs), the tool behind a new wave of gene therapies. AAVs resemble hollow balls. They can be filled with cargo, including human genes, and directed toward particular cell types. AAVs differ from other viruses in one key respect: They don’t cause illness. This built-in safety feature makes them attractive for therapeutic applications.

In May, we acquired AveXis, including its lead product candidate, AVXS-101, an AAV-based gene replacement therapy designed to treat a neurodegenerative disease called spinal muscular atrophy (SMA), the leading genetic cause of death in infants. AveXis has valuable AAV manufacturing capabilities to bolster our expertise.

Earlier in the year, we entered into a licensing agreement with Spark Therapeutics to register and commercialize its product Luxturna(voretigene neparvovec) – the first AAV-based therapy approved by the US Food and Drug Administration – in markets outside the US. Luxturna is designed to restore vision in patients with mutations in both copies of the RPE65 gene, a rare genetic condition that leads to total blindness by the time patients are in their mid-30s.

These agreements complement our existing programs, including an AAV collaboration with Homology Medicines. We began working with the company in 2017 to discover therapies for genetic blood disorders and eye diseases.

Other technology platforms are just beginning to emerge. Our scientists are exploring a new class of therapeutics called molecular glues. The cellular world is full of compounds that 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 medical conditions. Some of the proteins that glues target have for years been known to contribute to disease, yet conventional approaches to drug discovery have failed to yield medicines. Now some proteins that cannot easily be targeted by drugs may be glued to other proteins, enabling us to degrade them.

Advancing transformative therapies

We continue to use the effective, conventional tools of drug hunters to find new ways to successfully fight disease. Our teams focus on advancing small molecules and biologics with the potential to make a big difference for patients. In 2018, we made significant progress in several therapeutic areas, including neuroscience, oncology and ophthalmology. We launched new products for diseases with limited treatment options and laid the foundation for additional drug approvals.

Neuroscience

Our neuroscience pipeline has delivered innovative therapies to address unmet medical needs in migraine and multiple sclerosis. In partnership with Amgen, we received approval for Aimovig (erenumab) in the US, the EU and other markets for migraine prevention. Novartis co-commercializes Aimovig with Amgen in the US, and Novartis has the exclusive rights to Aimovig outside the US, except for in Japan. Migraine affects one in 10 people and is the third leading cause of disability in people under 50. Patients frequently suffer from recurrent, debilitating attacks, and until now, there have been no treatments specifically designed to prevent migraine. Aimovig blocks a protein signal that is believed to trigger the excruciating pain and other symptoms of migraine. In clinical trials, many patients on Aimovig reported more than a 50% decline in their monthly number of migraine days.

Multiple sclerosis (MS) is a debilitating disease in which the body’s immune system attacks the protective myelin coating that surrounds the brain and spinal cord. In total, MS affects 2.5 million people worldwide, with the disease occurring in different forms. Gilenya (fingolimod), our oral treatment for relapsing-remitting MS, received additional approval in the US and EU in 2018 as the first disease-modifying therapy for young patients with the disease. Young MS patients frequently suffer double or triple the relapse rates of adults, and clinical studies have shown that Gilenya reduces these rates by approximately 82% compared to interferon beta-1a, a standard MS treatment. We’re also advancing a different compound for the treatment of secondary progressive MS. Phase III clinical studies have shown that BAF312 (siponimod), our investigational oral treatment, delays disability progression in this form of MS, a first. We have filed in the US and EU for this indication.

Oncology

Our oncology pipeline delivered treatments for advanced breast cancer and melanoma in 2018. In July, we received a new approval for Kisqali in the US for women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. Kisqali is now the only CDK4/6 inhibitor approved for use with an aromatase inhibitor for the treatment of pre-, peri- or postmenopausal women in the US. It is also approved for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women.

We initiated global submissions for approval to market BYL719 (alpelisib) in combination with fulvestrant for postmenopausal women and men with HR+/HER2- advanced breast cancer who have progressed on or after an endocrine-based regimen. This combination nearly doubled the time to disease progression in patients with this mutation compared to fulvestrant alone in a Phase III clinical trial. If approved, BYL719 would be the first and only PI3K inhibitor for HR+ breast cancer.

Our combination treatment for melanoma, Tafinlar + Mekinist, received several approvals – including in the US and EU – for an additional indication as an adjuvant therapy for melanoma patients with a BRAF V600 mutation. Of the roughly 200 000 melanoma diagnoses made each year, nearly half of these are driven by a specific genetic mutation called BRAF. Tafinlar + Mekinist is one of the only combination treatments available as an adjuvant treatment for these patients, and clinical trials have shown that this option can be used to reduce the risk of death or cancer reappearance after tumors are removed via surgery.

Ophthalmology

We have also been working toward innovative therapies for eye diseases such as neovascular age-related macular degeneration (nAMD). nAMD is a leading cause of severe vision loss, affecting up to 25 million people worldwide, and current treatments require injections into the eye every four or eight weeks. In October, we announced additional positive results from Phase III studies of RTH258 (brolucizumab) in nAMD. RTH258 is a novel antibody fragment with the potential to significantly reduce the burden associated with the number of treatment injections needed for nAMD.