Deliver transformative innovation

The Novartis purpose is to reimagine medicine to improve and extend people’s lives. In our pursuit of transformative treatments, we explore possibilities to cure disease, intervene earlier in chronic illnesses, and find ways to improve quality of life. Our researchers harness emerging tools and technologies – or invent new ones – to make progress in medical science for patients.

Novartis continued to deliver transformative innovation for patients in 2020, including treatments for high cholesterol and multiple sclerosis, while advancing a strong and diverse pipeline of experimental therapies and exploring ways to battle COVID-19.

We received 26 approvals for new treatments as well as new indications for existing treatments in the US, the EU, Japan and China. These included the approval of Kesimpta in the US, the approval of Leqvio and Zolgensma in the EU, and the approval of new indications for Cosentyx in the US and the EU. In June, we received five approvals in one day in Japan. We also continued to add new molecules to our pipeline and advance key projects, with readouts from clinical studies setting the stage for further launches in 2021 and beyond.

Our approach to research and development

Novartis has an industry-leading pipeline that includes more than 40 assets in full development, including molecules that are being tested in more than one disease. Our consistent investment in research and development (R&D) – USD 9.0 billion in 2020 – helps us identify and advance promising treatments with the potential to help millions of patients. More than 20 000 associates work in research and development at Novartis.

We’re not afraid to take risks. In fact, researchers working to discover new treatments at the Novartis Institutes for BioMedical Research concentrate on drug targets and conditions that have been perceived as intractable for many years. And our Global Drug Development teams – responsible for designing and running large clinical trials – pursue projects where there is high unmet need for patients. Approximately 90% of our treatments in development have the potential to be first in class or first in a specific medical indication.

Our investment in research and development helps us identify and advance promising treatments with the potential to help millions of patients

Our leadership teams use a variety of lenses to evaluate our pipeline. We prioritize projects with the potential to transform the standard of care for patients. We assess the innovativeness of the biotechnology involved, with an eye toward applying it to other diseases. And we take access and global health into account: We aim to bring cutting-edge technology to populations around the world.

Pandemic response

The scale and scope of our R&D operations provided the foundation for a robust response to the COVID-19 pandemic. As the crisis unfolded, we convened a task force to examine every molecule in our portfolio for potential treatment of patients with COVID-19 as well as to determine how to protect the integrity of ongoing clinical trials.

We quickly designed and launched three Phase III, placebo-controlled trials to test promising hypotheses. One study was stopped early due to enrollment challenges. Although the other two studies showed negative results, they helped to improve the scientific understanding of the disease. We are also collaborating with Molecular Partners to develop two potential antiviral treatments for COVID-19 based on a new class of protein therapeutics known as DARPin^®.

We joined open science efforts to identify immediate solutions for COVID-19 patients and anticipate pandemics of the future

In addition, we initiated smaller place-bo-controlled studies and quickly provided our compounds to the external research and medical community upon request, supporting more than 30 clinical trials as well as nearly 7 000 patients with COVID-19 via compassionate-use requests from physicians, institutions and governments.

We joined open science efforts to identify immediate solutions for COVID-19 patients and anticipate pandemics of the future. For example, we’re working with researchers from the University of California, Berkeley, and other pharmaceutical companies to target a protein that’s essential for coronavirus survival. The goal is to find a molecule that blocks all coronaviruses, including the virus that causes COVID-19.

Data science and digital technologies

For the last few years, teams have been working to integrate and leverage massive amounts of data that once existed in silos at Novartis. We have hired data scientists, formed collaborations, and designed platforms and tools to aid the effort. We’ve also deployed cutting-edge digital technology across the organization. These are no longer pilot projects: We are taking advantage of our size and working to make the drug discovery and development process more efficient and effective.

These investments helped mitigate disruptions to our clinical trials when the pandemic struck. We were able to quickly scale up remote site monitoring and management activities to keep studies on track. More than 35 000 remote monitoring visits took place from March to the end of the year.

In parallel, we took steps to safeguard employees in critical roles who needed to be on site. Space booking tools – developed in a matter of weeks – helped associates maintain physical distancing while carrying out essential functions.

Our data scientists collaborated with experts in clinical operations to build a new tool that employs artificial intelligence and predictive analytics to anticipate COVID-19-related disruptions. It enabled teams to modify trial recruitment plans before issues arose.

A new digital recruiting platform for studies also proved useful. It leverages social media channels to inform patients or healthcare providers about trials that may be of interest to them. Potential participants can choose to visit a website, complete a brief screening questionnaire, and be contacted by a call center for more information. By the end of the year, the full platform had generated more than 140 pre-qualified leads to sites for three clinical trials, including a pivotal Phase III study.

Our data scientists collaborated with experts in clinical operations to build a new tool that employs artificial intelligence and predictive analytics to anticipate COVID-19-related disruptions

We continued to advance other digital priorities despite the pandemic. For example, we convene a team of experts to evaluate and prioritize data and digital opportunities for key assets.

Take CFZ533 (iscalimab), for example, an experimental immunomodulatory therapy with the potential to make kidney and liver transplants, which are often rejected by the immune system, durable. The Novartis team proposed using an algorithm to get an early indication of the compound’s effectiveness by determining the health of the transplanted organ with the goal of predicting its survival. We are collaborating with external academics to develop the algorithm using lab test and biopsy results from patients.

Advanced therapy platforms

A key part of our R&D strategy is to pursue new approaches to treating disease, such as by using genes and therapeutic viruses. If we prove that a new approach works for one condition, then we look for opportunities to apply it to others.

One of our leading gene therapy platforms, which employs adeno-associated viruses (AAVs), is a case in point. We use these benign viruses to deliver genes to cells inside the body. The goal is to repair them with a one-time treatment. In 2019, our AAV-based therapy Zolgensma was approved in the US for certain patients with a devastating neurodevelopmental disease called spinal muscular atrophy (SMA). We maintained momentum in 2020 by launching the drug in additional markets and continuing our efforts to develop an intrathecal formulation for use in older SMA patients.

We also expanded our AAV manufacturing capacity while advancing experimental AAV-based therapies for additional neurodegenerative diseases toward clinical testing. We made deals with biotechnology companies Dyno Therapeutics and Sangamo Therapeutics to explore new ways to engineer and use AAVs.

Another gene therapy platform involves a set of programmable molecular “scissors” called CRISPR. The idea is to permanently change cells by precisely snipping the DNA that’s found deep inside them. We’re developing a potential treatment for sickle cell disease with CRISPR technology licensed from Intellia Therapeutics. In 2020, patients began enrolling in a small clinical trial designed to test the treatment. It’s a gene therapy, but it’s also a cell therapy because cells are removed from the body and modified in a lab to generate the drug.

All of this work builds on our early successes with chimeric antigen receptor T-cell (CAR-T) therapy. Our flagship CAR-T therapy, Kymriah, was the first gene therapy approved in the US. It’s also a cell therapy: A patient’s T-cells are extracted and reprogrammed to recognize and fight cancer cells before being infused back into the body.

We’re designing new CAR-T therapies and exploring how to overcome resistance and relapse in a variety of difficult-to-treat cancers. We’re also piloting a new manufacturing platform that has the potential for higher efficiencies, shorter turnaround times and better outcomes. Our experimental treatments YTB323 and PHE885, manufactured using our innovative platform technology, recently entered clinical testing. In parallel, we’re optimizing the manufacturing process for Kymriah.

Another important platform is radioligand therapy, a targeted approach that has the potential to become a pillar of cancer treatment

Another important platform is radioligand therapy, a targeted approach that has the potential to become a pillar of cancer treatment. Each therapy consists of radioactive atoms that emit energy combined with molecules that can recognize and bind to specific types of cancer cells, no matter where they are in the body.

Our radioligand therapy, Lutathera, which is marketed by a Novartis company called Advanced Accelerator Applications, is approved for certain gastroenteropancreatic neuroendocrine tumors, which are rare. Teams are now testing the approach in more common cancers. For example, our experimental treatment¹⁷⁷Lu-PSMA-617 is currently in a pivotal clinical trial for an advanced form of prostate cancer. We expect to report results in 2021.

We’re also exploring ways to use RNA-targeting therapeutics to treat disease. These molecules recognize and initiate the degradation of mRNA, which carries instructions for protein synthesis from DNA, thereby blocking the production of specific proteins thought to be involved in causing disease. We received approval in the EU in December to market a small-interfering RNA molecule called Leqvio (inclisiran) for the treatment of primary hypercholesterolemia (high cholesterol) and mixed dyslipidemia. We are pursuing approval of inclisiran in the US and other markets. Three large clinical trials demonstrated that it significantly reduces LDL cholesterol in patients with the condition. Inclisiran was licensed from Alnylam Pharmaceuticals, Inc. and developed in collaboration with The Medicines Company, which Novartis acquired in early 2020.

Another example of research in this space is TQJ230 (pelacarsen), a novel experimental treatment licensed from Akcea Therapeutics. TQJ230 is an antisense oligonucleotide that targets the mRNA of apolipoprotein(a), a key component of lipoprotein(a), which is a genetically predetermined, causal and independent risk factor for atherosclerotic cardiovascular disease. It has the potential to be the first medicine approved to treat patients with elevated levels of lipoprotein(a) and established cardiovascular disease.

Finally, our researchers are 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. Novartis scientists are creating new, synthetic glues to short-circuit disease and treat serious illnesses. Four of our experimental glues have entered clinical testing for the treatment of certain cancers and immunologic and neurodegenerative diseases.

Advancing our strong and diverse pipeline

Our focus on cutting-edge treatments for serious diseases extends to our assets in full clinical development. We are advancing more than 160 projects, including more than 25 potential blockbuster medicines.

Our mid-stage portfolio deserves particular attention, with a number of compounds that have the potential to change the course of intractable illnesses. Take osteoarthritis, which affects more than 300 million people worldwide and is the leading cause of disability in adults due to degeneration of cartilage in the joints. Existing treatments focus on relieving symptoms rather than altering the progression of the disease. LNA043, discovered in our own labs, has the potential to protect and repair cartilage in the joints of patients with osteoarthritis. We are currently testing the experimental treatment in patients with knee osteoarthritis.

Our mid-stage portfolio deserves particular attention, with a number of compounds that have the potential to change the course of intractable illnesses

Other molecules born in our labs have the potential to transform the treatment of rare diseases. For example, we’re studying LMI070 (branaplam) in Huntington’s disease and SMA. And LNP023 (iptacopan) is being studied in several rare complement-driven diseases, including renal diseases with limited or no treatment options that often affect young patients. We reported promising interim results from Phase II clinical trials in C3 glomerulopathy and paroxysmal nocturnal hemoglobinuria.

Our teams continually challenge treatment paradigms and build on the success of established franchises. For example, our neuroscience researchers are working to develop targeted treatments that can significantly improve outcomes for patients with multiple sclerosis, a disease that we have worked on for decades. In August, the US Food and Drug Administration approved Kesimpta, the first and only self-administered, targeted B-cell therapy for patients with relapsing forms of multiple sclerosis.

As compounds are approved, researchers continue to generate and vet new assets for the pipeline. For example, our scientists are studying novel anti-inflammatory compounds that block a cellular danger sensor called the inflammasome. The inflammasome is implicated in a range of common diseases, including certain cancers, heart disease, fatty liver diseases and Alzheimer’s. We’re harnessing and contributing to a wave of scientific innovation that is opening new avenues to creating medicines of the future.