What lies beneath: the unsung story of biopharmaceutical innovation
By Corey Salsberg, Vice President and Global Head of IP Affairs, Novartis
Ingenuity is often portrayed as an archipelago of “Aha!” moments in an otherwise empty sea. Newton and the apple. Archimedes in his bath. Einstein in a daydream that revealed his theory of general relativity. Farnsworth in a cornfield whose neatly plowed rows became the basis for his invention of television. The list goes on.
Without doubt, invention and discovery are unpredictable endeavors: nonlinear and unexpected; one step forward, three steps back. But that does not mean that innovation is random. Quite the contrary, while “Eureka” moments surely have their place, true innovation –that which really touches and transforms human lives – is almost always more a product of the focus and persistence that comes with the pursuit of a mission than of a chance encounter with a wandering muse. As Thomas Edison famously put it, “genius is one percent inspiration and 99 percent perspiration,” or thereabouts. This makes perfect sense; for it is precisely the hard work and perseverance that is done towards a mission or a goal that provides the necessary context for those “Aha!” moments to arise, not to mention the uncelebrated before and after steps that enable the conversion of those bold ideas into the breakthrough innovations that they eventually become.
Nowhere is this more true than in the biopharmaceutical field. With an average research and development (R&D) timeline of 10-15 years, biopharmaceutical innovation – the kind that stops a child from contracting a disease, purges a virus from deep within the body, sends a tumor into complete remission, or transforms a death sentence into a manageable condition – neither starts nor stops with a single “Aha!” moment. It is an ongoing, complex, laborious process that begins with disheartening odds (sometimes ten-thousand-to-one), where failures and their many teachings are as important as successes, and where “success” cannot fairly be measured in a single dimension. That is why, at Novartis, we direct our work not merely toward the invention of medicines, but toward a far broader mission: “to discover new ways to improve and extend people’s lives”.
This broad mission provides the context and focus for our science-based approach to R&D, and for just about everything else we do, including our approach to patenting. As most WIPO Magazine readers will know, the patent system is a powerful tool that in our industry helps to offset the high costs and risks inherent in the type of R&D that we do. But, importantly, it is only that –a tool, a means to achieve an end, not an end in itself. In practice, this means that we focus on our mission, follow it wherever it takes us, and patent those inventions we create along the way that help us to realize and implement it. Anyone who takes the opposite approach –chasing patents for patents’ sake – is destined to end up with a file full of pricey paper, and is unlikely to achieve much else. That, in essence, is the core difference between mere invention and true innovation, the end goal that permeates our mission. It is also why, ironically, on World Intellectual Property Day, the best thing we can do to recognize the critical importance of the system is not to focus on intellectual property (IP) as such, but on the mosaic of results that it enables.
There are, of course, innovations that everybody sees – the pills in the bottle, the tablets in the blister pack, the ointment in the tube, the liquid in the ampoule – the stuff that saves millions of lives and shapes human history. Think of a medicine, look inside your own cabinets and pill boxes, reflect on any therapy that has given you or a loved one a new lease on life, and you can be sure that the patent system played a central role in its creation: antibiotics, vaccines, pain relievers, antiretrovirals, immunotherapies, nucleotide analog polymerase inhibitors, to name but a few.
Thanks to historic medicines like these, millions of potentially deadly infections are thwarted each year; life’s bumps, scrapes and headaches are easier to bear; cancer death rates are plummeting, cure rates for Hepatitis C are now above 90 percent (https://tinyurl.com/mgnscjn), and HIV/AIDS mortality has dropped 87 percent.
Let me cite a few examples from our own portfolio. Science-based innovation and the patents that enabled it gave us Glivec®/Gleevec®, a tyrosine-kinase inhibitor now on the World Health Organization’s essential medicines list. It has been called a “miracle drug” for its role in converting a once fatal cancer, chronic myelogenous leukemia, into a manageable chronic condition, and in 2016 was named “Discovery of the Decade” by the prestigious Prix Galien Foundation.
Our in-house discovery of Cosentyx®, a psoriasis treatment won Prix Galien’s “Best Biotechnology Product” award in 2016, and Entresto®, the first breakthrough in decades for heart failure with reduced ejection fraction, is now considered the new standard of care by the American College of Cardiology, the American Heart Association, the European Society of Cardiology among others.
A deeper innovation story
But while medicines as end products may win praise and make the history books, they are only the visible crest of a much deeper innovation story. Sadly, that story is not readily apparent to a casual observer and often goes untold. Look inside a modern car, and it is easy to see the incredible array of innovation that went into its creation. Medicines, by contrast, have no doors or hoods to open. But that does not mean that there is less innovation inside. A lot more goes into creating a medicine than just finding new substances and placing them in pills. Just as a car needs to be roadworthy – effective as a vehicle, safe to drive, consistently producible and compliant with regulatory standards – so a pharmaceutical substance must meet rigorous safety, efficacy and quality standards before it can be given to patients. This is far from an easy task, as evidenced by the fact that less than 12 percent of drug candidates entering clinical trials result in an approved medicine.
Getting into that “12 percent club” requires science, hard work and many different types of innovation. It may involve developing the safest, most effective or efficient form of a substance; formulating it with the right ingredients; figuring out the disease or conditions for which it is best suited; and determining the right dose and dosage form. It may also involve inventing new ways to manufacture the substance to scale and quality standards, which is particularly critical for complex biologics (large molecules) and biosimilars.
Then, of course, there are the other 88 percent – the projects that fail at the clinical stage. These are also part of the innovation story. Why? Because the road to failure is often lined with a host of interim successes, many of which will have application elsewhere. And because every “failure” is also a success if it sends us down a different path that ultimately yields a medicine. Though they may not make the headlines, these interim discoveries and developments (wherever they may arise) are the critical backstory to the precious few medicines that do make the grade. This is a narrative which deserves more prominence in the innovation story.
So, for that matter, does the chapter that comes after a successful medicine is marketed. In some respects, a marketed medicine is just another milestone on a longer road to improving and extending people’s lives (albeit an incredibly important one). While sometimes the next stop is a completely new medicine, often progress comes through incremental improvements to therapies that already exist.
Some argue that such improvements are trivial and do not merit patent protection. But patent laws have expressly sought to incentivize “improvements” for centuries. The first US Patent Act (1790), for example, awarded patents for “any useful art, manufacture, engine, machine, or device, or any improvement therein not before known or used.” Its author, Thomas Jefferson, later wrote in a letter to Marc Pictet: “many ingenious improvements are made in consequence of the patent-right.”
Indeed, ingenuity should not be assessed merely by reference to what came before. If the goal of the patent system is to encourage innovation, and innovations are inventions with meaningful impact, the appropriate question to ask of an otherwise patentable invention is not how much it builds on the past, but what it brings to our future. In the case of medicines, a new formulation can hardly be “trivial” if, for the first time, it allows a child to take a medicine previously reserved for adults (i.e. a pediatric formulation), or makes it possible to distribute an existing medicine to remote areas (e.g. heat resistant formulations).
Nor is there anything remotely trivial about the novel and inventive use of an existing medicine to effectively treat a different disease. These and many other types of improvements, which can translate into everything from reduced side effects, to broader patient use, to better compliance and health outcomes, form another crucial narrative in the innovation story that is too important to ignore.
There are others, too, like the critical role that IP plays in enabling generic medicines that are so important to today’s budget-conscious healthcare systems. Today’s generics are but copies of yesterday’s innovative medicines, made at lower cost by foregoing independent R&D and copying successful outcomes once patents expire. Tomorrow’s generics will likewise follow the lead of today’s innovative medicines, relying again on the IP-driven R&D undertaken by innovators to create new medicines.
There are also more complex narratives, like the central role that IP plays not just in enabling the invention of tomorrow’s cures, but in facilitating access to today’s medicines by creating the conditions that help ensure that medicines actually reach patients. Evidence shows that strong IP results in faster launch and more rapid access to new medicines; the introduction of medicines that would not otherwise be available in a given market (in brand or generic form); and investment in activities like building distribution chains and doctor and patient education which have been shown to lead to improved access and better health outcomes.
Then there are the myriad alternative ways in which we are able to apply our innovation expertise and global reach to advance public health and improve people’s lives. This includes our work in developing Coartem®, a cutting-edge anti-malarial which we have provided without profit to more than 60 malaria-endemic countries (over 800 million treatments to date). And social ventures, like our pioneering Novartis Access program which offers affordable access to a portfolio of our non-communicable disease medicines. It even includes innovative partnerships like our work with WIPO and the World Economic Forum to build an international platform (the Inventors Assistance Program) that brings developing country inventors into the global innovation ecosystem.
Last, there is perhaps the oldest narrative of all: “The only constant is change.” Science is changing as our understanding of disease rapidly evolves. Medicines are changing as we continue to transition from chemistry-based small molecules to biology-based large molecules, and from one-size-fits-all to personalized care. Technology is changing as once-disparate fields converge, bringing apps, software, data and wearables, even “smart lenses” and “chips-on-a-pill”, into medicine. With all these changes the innovation that defines our future will only grow more intricate, interconnected and complex.
Now, more than ever, the full picture of the role that IP and innovation play in extending and improving people’s lives needs to be brought to the surface. There is too much at stake to let it lie beneath.