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Kevin Foust, Senior Director of Research & Early Development at Novartis Gene Therapies, talks to Pharm Exec about his involvement in the development of Zolgensma, the first and only gene therapy approved to treat spinal muscular atrophy (SMA).
Novartis Gene Therapies’ Zolgensma is the first and only gene therapy approved to treat spinal muscular atrophy (SMA), a rare neuromuscular disease that is the leading genetic cause of infant death. The drug is designed to address the genetic root cause of SMA by providing a functional copy of the human SMN gene to halt disease progression through sustained SMN protein expression with a single, one-time IV infusion.
Gaining FDA approval in May 2019, the drug has since been approved in Japan, Europe and Brazil. Novartis Gene Therapies is pursuing registration up to three dozen countries, with regulatory decisions anticipated in Switzerland, Canada, Israel, Australia, and South Korea.
In October 2020, the company announced new interim data from the ongoing Phase III STR1VE-EU clinical trial for Zolgensma, demonstrating that patients with spinal muscular atrophy (SMA) Type 1 continued to experience significant therapeutic benefit, including some patients with more aggressive disease at baseline compared to previous trials.
In this interview, Kevin Foust, Senior Director of Research & Early Development at Novartis Gene Therapies, talks about his intrinsic involvement in the development of Zolgensma, and how he is applying that work to other rare diseases, including Rett syndrome, a rare disorder in children that combines the symptoms of autism, cerebral palsy, Parkinson’s, epilepsy and anxiety disorder.
Kevin Foust: My interest in gene therapy goes back to when I was 16 or 17. I read an article about the potential of gene therapy, especially with rare diseases, and from that point I was hooked.
My first real project in science was when I was a postdoctoral researcher at Nationwide Children’s Hospital, and my team and I were researching/developing a gene therapy for spinal muscular atrophy (SMA), a rare and devastating genetic disease that leads to progressive muscle weakness, paralysis and, when left untreated in its most severe forms, permanent ventilation or death.
What made my postdoc so wildly successful, in that sense, was that we discovered1 an adeno-associated virus (AAV) vector with new properties that could target motor neurons very well. We then showed proof of concept in mice that it robustly rescued the disease, and that ultimately led to the development of Zolgensma. By uncovering that these AAV9 vectors (the gene therapy platform used by Zolgensma) can cross the blood-brain-barrier to efficiently target the central nervous system, we were able to bring forth an exciting, new therapeutic delivery approach for gene therapy, and patients with SMA.
There is a glib half-joking reference that industry is “the dark side,” but I don’t think that’s the case. I wanted my career to be in the space where we take something off the bench and test in humans for the first time. I used to think that was academia, but it wasn’t until I joined industry that I realized that this is where I want to be to help advance translational sciences.
After nearly a decade in a university setting/academia, what brought me to industry in 2016 was really my discovery of the AAV9 vector and the real potential I saw it having. I didn't want to miss this opportunity and the chance to be a part of something that could have the potential to become a beneficial treatment for a particularly devastating disease.
What I’ve noticed is that everyone in industry is here for the same purpose — to help the patient — and is laser-focused on bringing something to someone that didn't exist before. This was super compelling to me.
It’s certainly been a journey to get here. Zolgensma has impacted more than 700 patients and it’s just so rewarding to know that we are making a difference in people’s lives. Our President, Dave Lennon, sends around these inspiring emails on Fridays where he’ll spotlight a patient and their family who has been impacted by the work Novartis Gene Therapies is doing. It still makes me emotional every time, whether it’s the 50th or 500th story — so many small milestones are made possible because of this treatment. I love reading about the little girl who was able to grab her sister’s hair, or about the little boy who was able to sit unassisted or touch his toes. Zolgensma is helping to transform the lives of these patients and their families.
I think it’s great that there are now so many options for patients that weren’t available just a few years ago. At Novartis Gene Therapies, we are dedicated to the SMA community and to reimagining the future of rare diseases. My hope is that we can continue to increase access for patients and the SMA community, with approvals in additional markets.
As we look to the future, the possibility of exploring Novartis Gene Therapies’ AAV9 technology for other indications/rare diseases is something that I look forward to, as well as seeing the transformational gene therapies that will follow.
There have been a lot of developments since the concept of gene therapy was introduced in the late 1970s. The first, successful, in-human gene therapy trial in 1990 was huge for the industry, but it wasn’t until the first gene therapy was approved by the FDA that you saw the industry start to pick up steam again.
For me, the discovery of AAV9 vectors as a CNS delivery platform for gene therapy treatment in 2008, as I briefly mentioned earlier, was a huge milestone — not just for gene therapy but also the rare disease community. It laid the groundwork for Zolgensma, which is the second gene therapy approved in the US and the first and only one-time gene therapy for SMA.
The manufacturing process for gene therapy has also been a huge advancement in the field. Gene therapy manufacturing is a long, complex, and sometimes manual process that requires multiple biological steps. Novartis Gene Therapies is one of the first companies in the world to have successfully scaled up manufacturing. It has built the world’s largest manufacturing capability for gene therapies with 1 million square feet of manufacturing space.
I'm excited about all the new things that are going to come but I think the next few years are key. We have attracted a lot of people to the space; one, because of the science and the medicine that can be created and two, because it’s possible to commercialize these therapies successfully. That involves partnering with regulatory agencies to better map landscape and movements.
What excites me is really the interest and all the things that are on the horizon; hopefully, we're bringing forward the right things. And that in the next few years, there will hopefully be curative medicines for patients in need.
My time outside of work has always been devoted to my family. My wife is a vet, so we are huge animal lovers. During the pandemic, we have been fostering kittens and decided to keep one of them. Her name is Faith. We also added some chickens. It has been nice being able to spend more time with the family since we have been home much more.
I miss the water cooler discussions and in person meetings. We’ve managed to keep the lab open and functioning. I get into the office once every week or two. Otherwise it is mostly back to back Teams meetings. I find the days when I get in the office to be rejuvenating.