Endocrine Society member Tina Gupta, MD, always possessed a passion for helping her patients with type 1 diabetes overcome their daily struggles. She gives Endocrine News an exclusive account of why she made the move to the biotech industry by joining Vertex Pharmaceuticals, thus ensuring that her enthusiasm for patient-centered care can now help as many people as possible living with type 1 diabetes.

I went into medicine to help as many patients as possible, and my passion for diabetes care led me to specialize in endocrinology. The time I was in clinic helping my patients with type 1 diabetes motivated me every day. I saw the struggles that they experienced and the burden that type 1 diabetes posed on their daily lives. However, in many ways, my patients were benefitting from several advancements in the field of diabetes medicine. They were living in a world with rapid-acting insulins, continuous glucose monitors, insulin pumps, and hybrid closed loop systems. Despite access to these therapies and technologies, the majority of patients were not able to achieve the clinical outcomes I wanted to see as their endocrinologist. Only about one in four people with type 1 diabetes achieve a target HbA1c of <7.0% which speaks to how complicated and challenging this disease is to manage.

As an endocrinologist, beyond the patients I managed with cystic fibrosis-related diabetes (CFRD), I wasn’t very familiar with cystic fibrosis and the latest advancements in treatments by a Boston-based company, Vertex Pharmaceuticals. Since then, I have learned that Vertex has approved medications to treat the underlying cause of CF for up to 90% of the CF patient populations and have clinical trials for the remaining 10%.

“No longer getting to care for my patients directly has been difficult. However, as we continue to research treatments for those living with type 1 diabetes, I remember their stories and hold hope for the future because we understand how relentless this disease is for individuals, families, and loved ones.”

When I learned that Vertex was planning to use that same relentless commitment to potentially treat the underlying cause of type 1 diabetes, I knew I needed to be part of it. The decision to leave my practice, my patients, and my colleagues was a difficult one. In a way, I felt like I was going into the unknown, but I strongly believed Vertex had the potential to fundamentally change the treatment landscape for people living with type 1 diabetes.

Vertex entered the type 1 diabetes space in 2019 with the acquisition of Semma Therapeutics, but the real story goes back decades earlier. The founder of Semma Therapeutics was Doug Melton, PhD. At the time he founded the company, he was at Harvard University where he had spent many years focused on researching type 1 diabetes treatments. Motivating this commitment was the fact that, more than 30 years prior, Melton’s infant son was diagnosed with type 1 diabetes (his daughter would also be diagnosed years later).

Melton’s wife, Gail, was carrying the daily burden of the disease for their family, working nonstop to monitor and manage the relentless demands of type 1 diabetes. She had to prick her son’s fingers and toes to check his blood sugar multiple times a day and to inject him with insulin to control his blood glucose levels. While she managed the daily burden for their family, Melton worked tirelessly in the lab. He turned away from his research on frog biology and refocused his energy on researching how to turn stem cells into islet cells in the lab with the hope of replacing the insulin-producing cells that have been destroyed in people with type 1 diabetes.

After decades of research, Melton and his small team found a way to manufacture a stem cell into an islet cell in the lab that was glucose sensing and insulin producing. The team unlocked the “recipe” of which genes and functions to turn off and on and generated billions of fully differentiated, insulin-producing beta cells grown from stem cells in the laboratory.

Conducting research with the lab-manufactured islet cells and bringing them into human clinical trials is the next big challenge. Dr. Melton knew his small Semma team would need some assistance. When Melton ran into one of his former students, David Altshuler, MD, PhD, in Boston in 2019, he shared the news that his team had produced islet cells that were secreting insulin in the lab. Altshuler is the Chief Scientific Officer at Vertex and reported the milestone to leaders within the company who quickly acquired Semma Therapeutics. Vertex has long focused on developing potentially transformative new therapies for diseases where they have a deep understanding of the underlying causal biology. Semma’s investigational research which aimed to manufacture islet cells to replace the ones missing in a person living with type 1 diabetes, aligned with Vertex’s scientific strategy. Melton was confident that Vertex, with its science, technology, manufacturing resources, and capabilities, would be in a position to advance cell therapy approaches in type 1 diabetes.

Fast forward to today: Vertex has continued to advance and invest in its investigational type 1 diabetes program. Melton left his lab at Harvard in 2022 to join the Vertex team, and, that same year, Vertex acquired ViaCyte, a biotechnology company focused on researching stem cell-derived cell replacement therapies as a potential treatment option for type 1 diabetes.

The type 1 diabetes team at Vertex has since grown significantly and advanced two investigational programs for type 1 diabetes to clinical trials. One is targeted at people with type 1 diabetes with impaired hypoglycemic awareness and a history of severe hypoglycemia. This approach requires ongoing immunosuppression with the aim to protect the transplanted cells from the body’s immune cells. Our other clinical trial is for the broader type 1 diabetes population. Vertex is investigating the same transplanted cells, but encapsulated in a proprietary device that is surgically implanted in the body. The device is designed to shield the cells from the body’s immune system. This therapy is being investigated without the use of immunosuppressive therapy. Both clinical trials are actively enrolling adults living with type 1 diabetes in the U.S. and outside the U.S.

What is Cell Therapy and Cell Encapsulation?

Cell therapies may be able to replace or repair damaged, mutated, or missing cells in a person’s body with the goal of treating the underlying cause or condition. They are being developed using a variety of different cells depending on the objective, including blood cells, pancreatic cells, or nerve cells. These cells may be made from pluripotent stem cells — a cell that is able to replicate and differentiate, or convert, into any specific cell type in the body.

In addition to cell therapy, cell encapsulation is being investigated to provide protection from the immune system by placing enough living cells to be potentially therapeutic within a specially designed encapsulation device. The encapsulation devices are designed with the goal of behaving like natural tissue by using a special barrier that is intended to prevent immune cells from passing through but allows for vascularization.

Cell encapsulation is an innovative tool that has the potential to help treat the underlying cause of diseases such as certain types of cancers, hemophilia, Parkinson’s disease and type 1 diabetes, among others, with the aim of preventing the immune system from detecting and potentially destroying the cells intended to treat these diseases.

Uncompromising Commitment to Type 1 Diabetes

As a clinician, I was at ease talking about HbA1c, continuous glucose monitor (CGM) metrics such as time in range, insulin pumps, and more. So, when I first began learning about what cell therapy and cell encapsulation are, it felt like I was reading science fiction. The concept that one could potentially restore endogenous insulin production to someone living with type 1 diabetes was interesting.

Realizing that this science is currently being researched, and that I have a chance to be part of the effort to potentially bring this to my patients if approved has been incredible.  

“As a clinician, I was at ease talking about HbA1c, continuous glucose monitor (CGM) metrics such as time in range, insulin pumps, and more. So, when I first began learning about what cell therapy and cell encapsulation are, it felt like I was reading science fiction. The concept that one could potentially restore endogenous insulin production to someone living with type 1 diabetes was interesting.”

I recall a time in clinic when I met a young man recently diagnosed with type 1 diabetes. He had been planning to become a pilot, but his diagnosis derailed that plan as being on insulin treatment prohibited him from entering the training program. I have never forgotten how his whole vision for his future changed due to the results from a single lab test.

Over the course of my career, I’ve spent many hours counseling patients who have been overwhelmed and in despair about the unrelenting burden of their disease. While we endocrinologists provide care and guidance to these individuals periodically throughout the year, people living with type 1 diabetes must manage their disease 24 hours a day, seven days a week, for their entire lives. They must give themselves insulin multiple times a day to keep their blood sugar from being too high. However, there’s a delicate balance between blood sugar that’s too high (not enough insulin) and too low (too much insulin), and these levels are impacted by just about every aspect of daily life — diet, exercise, sleep, stress, and more.

Abnormally high or low blood sugar levels can be immediately life-threatening, and chronic high blood sugar levels lead to increased risk of serious long-term complications including damage to the eyes, kidneys, nervous system, and heart.

Insulin treatment and technologies like insulin pumps and CGMs have improved the lives of people with type 1 diabetes, their families and caregivers, but there is more work to do to hopefully develop a treatment that would target the underlying cause of the disease. At Vertex, our researchers and scientists are investigating potential cell therapies to treat type 1 diabetes. However, our work in the lab is not enough. Our entire team is working ceaselessly to better understand the physical and psychological burdens of living with type 1 diabetes. Whether it is the constant decision-making involved in insulin injections and blood sugar monitoring or dealing with and troubleshooting the multiple demands of CGM and pump technologies, it is vital our team understand that daily experience as best we can to help us reach our goal of bringing transformative therapies to people with type 1 diabetes.

Patients Come First

One of the things that is unique about the Vertex’s drug development process is that it is always about the patients. People living with type 1 diabetes are at the heart of everything we do. So, what are the highest impact ways to better understand what it is like to live with type 1 diabetes? It starts by establishing relationships and building trust, by talking to as many people living with type 1 diabetes as possible, by involving their caregivers and health care teams, and by learning from patient advocacy groups. To this end, we have a type 1 diabetes patient and caregiver panel that meets throughout the year to provide insights and feedback to our team on a variety of topics so we can better understand the patient’s experience, as well as learn more about their needs. Finally, we continue to work with the type 1 diabetes patient advocacy community, learning about their efforts to support, educate, and advocate for people with type 1 diabetes and understanding more about how we can help support the type 1 diabetes community.

Vertex’s commitment to patients is strong and has been the guiding light that has gotten us to where we are. I share that commitment and know it is my responsibility to take what I learned from my patients, mentors, and colleagues and amplify their voice and needs. Vertex truly understands the importance of going beyond research and development to engage in advocacy, awareness, and community support, and those living with type 1 diabetes, like my former patients, are at the heart of everything we do. As we advance our work in type 1 diabetes, we will continue to look to the patient and healthcare professional community for education, inspiration, and motivation.

No longer getting to care for my patients directly has been difficult. However, as we continue to research treatments for those living with type 1 diabetes, I remember their stories and hold hope for the future because we understand how relentless this disease is for individuals, families, and loved ones.

My wish would be to one day sit with my former patients and recall how we used to review their pumps and CGMs, recalculate their doses. In short, I hope to someday talk about how patients are treated today in historical terms.

Gupta is an associate medical director on the type 1 diabetes Medical Affairs team at Vertex Pharmaceuticals.  She received her BA and MD from the University of Tennessee. Her medical education continued at Boston Medical Center where she completed her internal medicine residency, followed by a fellowship for endocrinology, diabetes, and metabolism at Brigham and Women’s Hospital. Prior to joining Vertex, she worked as a clinical endocrinologist at Massachusetts General Hospital, specializing in diabetes, bone metabolism, and adrenal disorders.