Amarna Therapeutics Secures Regulatory Guidance From FDA for Diabetes Gene Therapy AM510

Amarna Therapeutics has received regulatory guidance from the FDA regarding AM510, its investigational gene therapy product intended to treat type 1 diabetes (T1D), in the context of an Initial Targeted Engagement for Regulatory Advice (INTERACT) meeting.¹

Amarna noted that the meeting, which took place on July 31, 2024, provided the company with feedback on the overall development plan for AM510, which currently remains a preclinical-stage program. Furthermore, Amarna specifically noted that the discussion in particular focused on chemistry, manufacturing, and controls; the nonclinical program; and the planned clinical trial design from a safety perspective. Amarna plans to incorporate the feedback as it progresses towards submission of an investigational new drug (IND) application for the therapy; notably, it stated that it anticipates a pre-IND meeting in less than 2 years. The company additionally noted that the meeting, which was held virtually, included participation from Amarna’s teams in both Leiden and Seville, some members of the company’s T1D scientific advisory board, and regulatory consultants from Veristat.

"Our AM510 tolerance induction program for T1D just hit a major milestone with the FDA INTERACT meeting,” Henk Streefkerk, MD, PhD, the chief executive officer and medical director of Amarna Therapeutics, said in a statement.¹ “We received extremely valuable feedback, confirming our integrated development strategy and outlining a clear regulatory path. We're eager to push forward with our preclinical work towards a successful pre-IND meeting, because we want to start treating and hopefully curing T1D patients as soon as possible."

AM510 is based on Amarna’s Nimvec platform. The platform is intended the circumvent triggering an immune response, which can negatively affect efficacy and prevent redosing in some gene therapy modalities. Amarna stated that in animal model research AM510 demonstrated the ability to delay the onset of hyperglycemia and to prevent the development of T1D.

AM510 is not the only advanced therapeutic currently in development for T1D. In June 2024, Vertex Pharmaceuticals reported data regarding VX-880, its investigational, allogeneic, stem cell-derived, fully differentiated insulin-producing islet cell therapy, at the American Diabetes Association 84th Scientific Sessions, held June 21-24 in Orlando, Florida.² The data, which came from the phase 1/2 FORWARD trial (NCT04786262), were presented by investigator Piotr Witkowski, MD, PhD, Professor of Surgery, Director, Pancreatic and Islet Transplant Program, University of Chicago, Illinois. Following a single infusion of VX-880 at the full dose, all 12 patients demonstrated islet cell engraftment and glucose-responsive insulin production by Day 90. Most adverse events (AEs) were mild or moderate and corresponded to the immunosuppressive regimen used in the study, the infusion procedure, and underlying disease.

“The data we’ve seen to-date in this study are extremely exciting,” Witkowski said in a statement.³ “Stem cell-derived islets regulate blood glucose control as well as natural human islets. The marked improvements seen across several key glycemic measures, the elimination of severe hypoglycemic episodes, and the reduction or total elimination of reliance on exogenous insulin have the potential to fundamentally change the treatment landscape for T1D and alleviate the significant burden this disease carries for patients.”

Also of note are Kadimastem and iTolerance, which are developing iTOL-102, a cell therapy that combines Kadmastem’s Islet Rx cell technology with iTolerance’s iTOL-100 immunomodulatory technology.⁴ IsletRx consists of insulin-secreting, human pancreatic islet-like cell clusters, and iTOL-100 is designed to enable tissue mismatched, allogeneic cell transplantation without the need for chronic immunosuppression. The companies requested an INTERACT meeting with the FDA in November 2023.

REFERENCES
1. Amarna Therapeutics receives constructive feedback from FDA INTERACT meeting for AM510 gene therapy development targeting type 1 diabetes. News release. Amarna Therapeutics. August 27, 2024. Accessed August 29, 2024. https://www.amarnatherapeutics.com/news/17/77/Amarna-Therapeutics-Receives-Constructive-Feedback-from-FDA-INTERACT-Meeting-for-AM510-Gene-Therapy-Development-Targeting-Type-1-Diabetes.html
2. Expanded FORWARD Trial Demonstrates Continued Potential for Stem Cell-Derived Islet Cell Therapy to Eliminate Need for Insulin for People with T1D. News release. ADA. June 21, 2024. Accessed August 29, 2024. https://diabetes.org/newsroom/press-releases/expanded-forward-trial-demonstrates-continued-potential-stem-cell-derived
3. Vertex Announces Positive Results From Ongoing Phase 1/2 Study of VX-880 for the Treatment of Type 1 Diabetes Presented at the American Diabetes Association 84th Scientific Sessions. News release. Vertex Pharmaceuticals. June 21, 2024. Accessed August 29, 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-positive-results-ongoing-phase-12-study-vx-880
4. Kadimastem and iTolerance Submit Initial Targeted Engagement for Regulatory Advice on CBER Products (INTERACT) Meeting Request with FDA for Potential Cure for Type 1 Diabetes. News release. Kadimastem. November 7, 2023. Accessed August 29, 2024. https://finance.yahoo.com/news/kadimastem-itolerance-submit-initial-targeted-120000679.html