Imagine a medicine so targeted it pinpoints the genetic cause of a disease—at the DNA or RNA sequence level—and treats it right at the root. Only a short time ago, that concept seemed impossible, but as we’ve increased our understanding of biology and genetics, and had significant advancements in biotechnology, scientists are on the cusp of treatments—and cures—for some of our most devastating diseases.
When we talk about progress in DNA and RNA-based therapies—referred to as genetic medicine—the conversation often leads to the impact this innovation could have on rare diseases or areas where we haven’t made significant progress with traditional, non-genetic-based therapies. While the impact in diseases like Huntington’s disease or Gaucher’s disease would be significant, advancements in genetic medicine could also move us leaps and bounds in more common, chronic disease areas.
Genetic medicines make up 25% of our therapeutic pipeline at Lilly. Our emerging therapies in this category have the promise to significantly change the lives of 415 million people living with diabetes, obesity and cardiovascular disease.
These are diseases that require constant, life-long management, and often people living with these conditions are unable to maintain treatment. The innovation on the horizon means these chronic diseases could be managed in an entirely new way—genetic medicines have the potential to be far more targeted and dosed infrequently.
How could genetic medicines target cardiovascular disease?
Cardiovascular disease refers to a group of disorders of the heart and blood vessels. In the field, scientists have made the most progress studying genetic medicines related to this disease area. Ruth Gimeno, group vice president of Diabetes and Metabolic Research at Lilly, is spearheading our genetic medicine application to cardiovascular disease.
“In cardiovascular disease, we know that an individual’s genetic profile contributes significantly to their overall disease risk,” Gimeno said. “Scientists have made great strides in identifying specific genes that predispose or protect people from cardiovascular disease, and we see significant promise in how we can leverage this information to more precisely target the causes of cardiovascular disease.”
There are proteins (Lpa(a), ANGPTL3 and ApoC3) derived from the liver that regulate how the body metabolizes lipids (including cholesterol). People who inherited beneficial variants of these proteins can better reduce lipid levels, helping protect them from cardiovascular disease. Individuals with detrimental variants, that increase the levels of harmful lipids, may experience early onset disease.
Our siRNA-based therapies are designed to block production of certain proteins, mimicking beneficial variants. Remarkably, the effects of a single siRNA dose can last for months or potentially even a year, making these therapies very durable.
By addressing cardiovascular risk factors that cannot be managed with conventional approaches, these siRNA-based therapies address a significant unmet medical need in cardiovascular disease, while at the same time making treatment easy and more convenient for patients.
In the future, we envision that genetic medicine can go beyond treating diseases to providing cures. Using a technology called gene editing, it is possible to insert beneficial genetic variants directly into an individual’s genome. This would permanently convert a detrimental gene to a beneficial one. With this, we may be able to create a one-and-done treatment for people at high risk of cardiovascular disease based on their genetic make-up.
Advancements in gene therapies for diabetes, obesity
While cardiovascular disease leads the way in genetic medicines, these therapies also have great potential to transform the way we treat diabetes and obesity. These are common diseases that affect millions of people. In diabetes, pancreatic beta cells—the cells that make insulin—are destroyed by an autoimmune assault or become non-functional under conditions of stress.
“The targets we'd like to modulate in beta cells often can't be addressed with traditional modalities,” explained Gimeno. “If we can figure out how to deliver genetic medicines to the beta cell, we could modulate causative genes and potentially restore beta cell function.
For both diabetes and obesity, hundreds of genetic variants that contribute to disease severity and progression have been identified. If we can understand which constellation of genes most predisposes to certain diseases and identify genetic levers that most effectively decrease disease risk, we may be able to use genetic medicines to pursue entirely new classes of treatments for these diseases, possibly allowing more precise tailoring of therapies and maybe even cures.
“In obesity, we are at the cusp of having truly effective therapies for chronic weight management, but these will need to be dosed on an ongoing basis. Genetic medicine has the potential to bring infrequently dosed medicines to the obesity space, making this a much more easily managed condition,” Gimeno added.
Our hope for the future
We have several early-phase clinical trials studying genetic medicines across diabetes, cardiovascular disease, neurodegenerative diseases and immunological disorders. Our increased focus and commitment to advance RNA and DNA-based medicines is fueled by the $700 million investment in the Lilly Institute for Genetic Medicine, moving to a new headquarters in 2024.
The possibilities to come from genetic medicine are potentially limitless. That means new-found hope for millions of people—those living with currently untreatable diseases and those living with chronic, hard-to-manage diseases.
Ruth was recently named one of the top 20 women leading biopharma research and development in Endpoints’ Women in Biopharma 2022 awards. Learn more about her trailblazing work in diabetes, obesity and cardiovascular diseases at Lilly here.
Advancing genetic medicine R&D in Lilly labs
00:01-00:16
[The video begins with a few snapshots depicting the history of Eli Lilly and how the company’s relationship with Cambridge has evolved over the years while Andrew C. Adams narrates in the background. The scene then transitions to a shot of the narrator speaking, followed by a depiction of genetic medicine work.]
Caption:
Andrew C. Adams, PhD
Co-Director, Lilly Institute for Genetic Medicine
Vice President, Neurodegeneration Research
Andrew C. Adams (Narrator):
Cambridge has had a really interesting history with Lilly. This was originally a delivery and device-focused site, where we worked a lot on solutions for patients with diabetes. But more recently, Cambridge has become a place where we’ve started doing genetic medicine work.
00:17-00:33
[The scene transitions to a man working in a laboratory followed by quick shots of Sarah Clark, Zeshan Ahmed, and Michelle Lynn Hall speaking.]
Caption:
Sarah Clark, PhD
Senior Director
Delivery & Device Innovation
Zeshan Ahmed, PhD
Associate Vice President
Neuroscience Next Generation Therapeutics
Michelle Lynn Hall, PhD
Associate Vice President
Genetic Medicine
Narrators:
Sarah Clark: Genetic medicines gives us an opportunity to address disease states in a completely new way.
Zeshan Ahmed: There’s a lot more that needs to be discovered and understood, but the potential for them is just amazing.
Michelle Lynn Hall: Its potential utility is, in theory, limitless.
00:34-00:46
[Close-up shots of people working on laboratory slides followed by a zoomed-in shot of a laboratory machine appear on the screen as Andrew narrates.]
Andrew C. Adams:
To make the kind of impact that the scale of Lilly demands, we really have to take these therapies to bigger diseases, to things like Alzheimer’s, to things like heart disease and cardiovascular disease. And that’s what we’re working on.
00:47-01:04
[A woman wearing gloves and a mask works in a laboratory as Michelle narrates. This scene is then followed by a frontal shot of Michelle speaking which then transitions to different women working in laboratories. The scene ends with a close-up shot of a person operating a device and some images being generated on a monitor.]
Michelle Lynn Hall:
We’re very invested in treating the central nervous system, the peripheral nervous system with genetic medicines or genetic nanomedicines and at the same time, building out platforms for other tissues and applications which we think might be opportunistic.
01:05-01:27
[The scene transitions to James MacKrell speaking, which is followed by shots of people working with slides and machines in laboratories while wearing masks and gloves. The scene then cuts to Michelle speaking.]
Caption:
James MacKrell, PhD
Associate Vice President
Venture Sciences
Narrators:
James MacKrell: What we’re here to do as Lilly employees, it’s really to bring medicines to patients. Internally, we have a strong team within genetic medicine working with the therapeutic areas to do that. We know that some of this innovation will come from the external environment.
Michelle Lynn Hall: If you want to invest in genetic medicine, literally everyone is right here in, I would say, one square mile, the biotech mecca of at least North America.
01:28-01:46
[The scene cuts to a man and woman working on their laptops and talking to each other in a room as Fariha Chaudry begins the narration. A frontal shot of Fariha appears on the screen as she continues to speak. This is followed by a shot of a woman working on a laptop.]
Caption:
Fariha Chaudry
Head of Global Brand Development
Connected Care
Fariha Chaudry:
The Boston area, while we have other pharma colleagues nearby, affords us the opportunity to be near other industries so we can pull in new and innovative ideas. And beyond that, we’re a stone’s throw away from some of the most well-respected universities in the world.
01:47-02:07
[James MacKrell starts speaking as the scene transitions to two women working and discussing something, and then to James speaking. This is followed by a quick shot of a man working in a laboratory. The scene then cuts to Michelle speaking, which is accompanied by a shot of people discussing something in a room.]
Narrators:
James MacKrell: The individuals who are coming into the site are coming in with very fresh ideas and coming in with new ways to do work.
Michelle Lynn Hall: We have all of the benefits of big pharma: infrastructure, resources, an infinite pool of people with seemingly infinite knowledge, but at the same time, we’re small, and so we can be agile and nimble.
02:08-02:29
[Zeshan starts narrating as the scene shows a person operating a monitor. The scene then cuts to Zeshan speaking while sitting on a sofa followed by a shot of a man working in a laboratory as Sarah and Andrew continue the narration.]
Narrators:
Zeshan Ahmed: The data, the science is constantly changing. The quicker we can respond to the data, to those changes, the better the science is.
Sarah Clark: What’s exciting about the future of genetic medicines is that Lilly is diving in with both feet.
Andrew C. Adams: I think we’re at the start of a revolution in genetic medicine, and we wanted Lilly as a company, to be part of that revolution.
02:30-02:37
[Lilly logo appears on the screen in red text on a white background.]