The FDA has given the green light for a Phase 2a clinical trial of Progerinin, an investigational drug aimed at treating Hutchinson-Gilford Progeria Syndrome (HGPS), commonly known as Progeria. This ultra-rare genetic condition, affecting approximately 1 in 18 million people, causes accelerated aging in children, who typically die of heart disease around age 14.5.
The trial, a collaborative effort between PRG Science & Technology Co., Ltd. (PRG S&T), The Progeria Research Foundation (PRF), Boston Children’s Hospital, and contract research organization Amarex, will assess the safety and efficacy of Progerinin in combination with Zokinvy, the current standard of care. Zokinvy, approved by the FDA in 2020, EMA in 2022, and Japanese MHLW in 2024, has been shown to increase lifespan in a Progeria mouse model by 25%.
Study Design and Rationale
The Phase 2a trial is a randomized, open-label study that will enroll 10 patients aged one year and older with Progeria and Progeroid Laminopathies (PL). Progerinin will be administered alongside Zokinvy. The rationale behind the combination therapy lies in their distinct mechanisms of action. Zokinvy inhibits the development of the toxic protein progerin, while Progerinin appears to reduce the overall level of progerin in the body.
Preclinical data published in the journal Cells in April 2023 indicated that Progerinin could potentially increase lifespan in a Progeria mouse model by 50%. Bumjoon Park, president of PRG S&T, stated, "This clinical trial demonstrates PRG S&T’s R&D capabilities to improve access to new drugs and expand treatment opportunities for children with progeria worldwide."
Progeria and the Role of Progerin
Progeria is caused by a genetic mutation in the LMNA gene, leading to the production of progerin. This abnormal protein accumulates in cells, causing progressive damage and atherosclerotic heart disease. Audrey Gordon, Esq., Executive Director of PRF, emphasized the importance of this trial: "Each Progeria clinical trial builds on learnings from our previous trials, so that we are continually making progress toward even better treatments and the cure."
Interestingly, progerin is also produced at lower rates in the general population as part of the natural aging process. This connection suggests that research into Progeria could provide insights into treating age-related conditions like heart disease and stroke.
Future Directions
PRG S&T is also developing PRG-N-01, a treatment for neurofibromatosis type 2. A Phase 1/2 trial of PRG-N-01 is underway in South Korea. The company aims to develop first-in-class innovative new drugs for rare genetic diseases. Dr. Kush Dhody, President of Amarex Clinical Research, added, "Patients with Progeria and their families deserve more options… We're honored to support a study that brings more hope to these patients."
