CGTLive's Pillars of Progress 2023: Top News in Endocrinology

For all of 2023, the CGTLive^™ team was following along the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders. These efforts included holding in-depth conversations with experts in the clinical care of these individuals, as well as in cell and gene therapy development, culminating in our coverage of each step of progress that the most exciting cellular and genetic treatments have made along the pipeline.

From major data publications and presentations to FDA decisions and major medical meetings, the team spent all year bringing the latest information to the website's front page.

Among our areas of focus in 2023 has been endocrinology, a field that saw several treatments move through the pipeline, as well as others that made key steps toward a meeting with the FDA. The major news items appeared among the top pieces our team produced—but sometimes smaller stories reach those heights as well because of their clinical impact, their inventive mechanisms, or otherwise. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in endocrinology over the course of 2023.

Here, we'll highlight some of the most-read content on CGTLive's endocrinology page this year. Click the buttons to read further into these stories.

1. Vertex Doses First Patient in Phase 1/2 Trial of VX-264 in Type 1 Diabetes

• The trial is assessing safety, tolerability, and efficacy of using encapsulated islet cells.
• VX-264 utilizes the same stem cell-derived islets as VX-880, which recently met primary end points in a phase 1/2 study.
• The trial employs a sequential approach, with partial and full doses administered in different stages.

August 1, 2023 — Vertex Pharmaceuticals announced amid its quarterly financial results that it had dosed the first patient in its newest cell therapy program, the phase 1/2 trial (NCT05791201) of VX-264, a fully differentiated islet cell therapy, in patients with type 1 diabetes mellitus. The trial is still enrolling patients, and is designed as a sequential, multipart study aimed at evaluating safety, tolerability, and efficacy of VX-264. As of the latest update on July 27, 2023, the estimated enrollment was 17 patients.

“We are excited to see our second program in T1D advancing into the clinic and look forward to bringing transformative, if not curative, therapies to T1D patients who are waiting."

– Bastiano Sanna, PhD, of Vertex

2. Patients With T1D Achieve Insulin Independence Following Implantation of Cell Pouch System and Islet Transplant

• Five patients achieved insulin independence after receiving Sernova’s Cell Pouch System in a phase 1/2 clinical trial.
• Sernova reported persistent islet function in patients from another cohort with the 10-channel Cell Pouch, with 1 showing sustained serum C-peptide levels after a single islet transplant.
• Preclinical data showed glycemic control normalization in a diabetes mouse model, and Sernova plans an investigational new drug application for a combined Cell Pouch and iPSC ILCs trial in 2024.

June 26, 2023 — Five patients with type 1 diabetes (T1D) with severe hypoglycemia unawareness who were implanted with Sernova’s Cell Pouch System, an investigational medical device containing immune protected therapeutic cells, achieved insulinin dependence following islet transplant to the Cell Pouch and supplemental portal vein islet infusion. The 5 patients were among 6 patients being evaluated in the first cohort of a phase 1/2 clinical trial (NCT03513939) for the Cell Pouch System at the University of Chicago. The sixth patient in the cohort is still awaiting assessment of islet graft function.

"I continue to be encouraged by the results achieved in this trial, and especially by the ease of use and favorable response from a single islet transplant to the larger Cell Pouch."

– Piotr Witkowski, MD, PhD, of UChicago

3. FDA Approves Lantidra Cell Therapy for Type 1 Diabetes

• The allogeneic pancreatic islet cell therapy offers an additional treatment option to achieve target blood glucose levels.
• Donislecel, administered through a single hepatic portal vein infusion, aims to address unmet needs in type 1 diabetes treatment, specifically hypoglycemia.
• The approval follows a prolonged regulatory process, including an advisory committee meeting in 2021 where donislecel received a favorable vote.

June 28, 2023 — The FDA approved CellTrans’ donislecel allogeneic pancreatic islet cell therapy under the name Lantidra, for treating adults with type 1 diabetes (T1D) who are unable to approach target glycated hemoglobin because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education. Donislecel is designed to secrete insulin, removing the need to take insulin to control blood sugar levels in some patients with T1D. The therapy is administered as a single infusion into the hepatic portal vein and an additional infusion may be given depending on the patient’s response to the initial dose.

"Today’s approval, the first-ever cell therapy to treat patients with type 1 diabetes, provides individuals living with type 1 diabetes and recurrent severe hypoglycemia an additional treatment option to help achieve target blood glucose levels.”

– Peter Marks, MD, PhD, of the FDA

4. Insulin-Producing Islet Cell Therapy VX-880 Meets Primary Efficacy End Point in Patients With Type 1 Diabetes

• The consistent positive outcomes observed across multiple patients and endpoints in the phase 1/2 trial are considered highly unusual and offer hope for transformative therapies in type 1 diabetes.
• Notably, the normalization of HbA1c without the need for exogenous insulin one year after therapy with VX-880 is considered a significant advancement.
• The positive outcomes have prompted the trial to proceed to Part C, where patients will receive the full target dose of VX-880.

June 23, 2023 — Two patients with type 1 diabetes (T1D) with impaired hypoglycemic awareness and severe hypoglycemic events (SHEs) who were treated with Vertex Pharmaceuticals’ VX-880, an investigational allogeneic insulin-producing islet cell therapy being evaluated in a phase 1/2 clinical trial (NCT04786262), have experienced an elimination of SHEs and shown a reduction in HbA1c that met the criteria for the study's primary efficacy end point.

“The reproducible efficacy across multiple patients and end points, including the level of glucose control and the elimination of SHEs, observed in this trial is highly unusual in T1D patients treated with exogenous insulin, wherein only ~25% of people with T1D meet the recommended HbA1c target of 7.0%, and is truly remarkable.”

– Trevor Reichman, MD, FRCSC, of UToronto

5. Gene Therapy Improves Quality of Life in Patients With Glycogen Storage Disease Type 1a

• The therapy significantly reduced daily cornstarch intake, with a mean 70.0% reduction in total daily cornstarch intake from baseline to week 52.
• Quality of life assessments revealed positive outcomes, with patients reporting improved energy, stamina, mental clarity, sleep quality, and overall quality of life.
• The phase 3 trial (NCT05139316) is fully enrolled, with results expected in the first half of 2024.

May 16, 2023 — DTX401, an investigational adeno-associated virus serotype 8 (AAV8) vector gene therapy expressing the human G6PC gene, showed a positive efficacy and safety profile in all patients with glycogen storage disease type 1a (GSD1a) treated in a phase 1/2 clinical trial (NCT03517085) at 1 year. Data from the trial were presented in a clinical trial symposium at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California.

“To keep these patients alive, they need a continuous source of exogenous glucose 24/7... Despite very strict rigorous nutritional management, they continue to have glycogen accumulationin their liver and kidneys, and this can lead to liver damage. They are at high risk of developing hepatocellular adenoma, which can progress to carcinoma; renal injury; proteinuria... Obesity is a problem, and metabolic micronutrient deficiencies is an issue.”

– Andrew Grimm, MD, PhD, of Ultragenyx