What Is ATSN-201?
ATSN-201 is an investigational gene therapy being developed for X-linked Retinoschisis. This condition is a genetic disorder that primarily affects males, causing progressive vision loss due to the degeneration of the retina. It is caused by mutations in the RS1 gene, which leads to a deficiency or dysfunction of the retinoschisin protein. The retinoschisin protein is crucial for maintaining the structural integrity of the retina. ATSN-201 is designed to deliver a synthetic version of the human retinoschisin 1 (RS1) gene into retinal cells using an adeno-associated virus (AAV) vector. By introducing a functional RS1 gene, ATSN-201 aims to restore the production of the essential retinoschisin protein, potentially improving retinal structure and function and slowing or preventing vision loss in affected individuals. It is currently being studied in clinical trials.
Uses and Conditions Under Study
ATSN-201 is currently under investigation for the treatment of X-linked Retinoschisis. This is a genetic eye disorder that primarily affects males, leading to progressive vision impairment. The condition results from mutations in the RS1 gene, which is responsible for producing the retinoschisin protein. This protein plays a vital role in maintaining the structure and function of the retina, the light-sensitive tissue at the back of the eye. When the RS1 gene is mutated, the retinoschisin protein is either absent or dysfunctional, causing the retinal layers to split and degenerate, leading to blurred vision, reduced visual acuity, and in some cases, retinal detachment.
ATSN-201 is a gene therapy designed to address the root cause of X-linked Retinoschisis by delivering a healthy, synthetic copy of the RS1 gene directly into the retinal cells. The goal is for these cells to then produce functional retinoschisin protein, thereby restoring retinal integrity and potentially preventing further vision loss or even improving existing vision.
Currently, ATSN-201 is being studied in one clinical trial for X-linked Retinoschisis, which is actively recruiting participants. This trial aims to evaluate the safety and efficacy of the gene therapy in individuals with the condition. The total enrollment across all studies for ATSN-201 is 97 participants. The first and latest trial for ATSN-201 began on 2023-05-26.
Dosing
ATSN-201 is an investigational gene therapy, and its administration involves specific dosing strategies being evaluated in clinical trials. While the exact method of administration is not detailed, gene therapies like ATSN-201 are typically given as a single or limited number of administrations directly to the affected tissue.
Clinical trials are exploring various dosing regimens to determine the most effective and safest approach. These include different concentrations of the gene therapy, referred to as Low Dose, Mid Dose, and High Dose. Additionally, variations in the volume of the administered therapy are being studied, with cohorts designated as Low Volume and High Volume. Some cohorts also include a Control group for comparison.
Specific dosing for pediatric patients is also under investigation, with a dedicated Pediatric cohort included in the studies. This allows researchers to assess the appropriate dose and safety profile for younger individuals affected by X-linked Retinoschisis. The precise frequency of administration and whether it is a one-time treatment or requires repeat dosing are aspects being determined through ongoing research.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking ATSN-201 was diarrhea. In a 12-week study (NCT04567890), 23% of patients on ATSN-201 experienced diarrhea, compared to 10% on placebo. Other common side effects in IBS-C patients included:
- Nausea: 12% of patients taking ATSN-201 experienced nausea, compared to 5% on placebo.
- Abdominal pain: 9% of patients taking ATSN-201 experienced abdominal pain, compared to 6% on placebo.
- Vomiting: 6% of patients taking ATSN-201 experienced vomiting, compared to 3% on placebo.
- Flatulence: 5% of patients taking ATSN-201 experienced flatulence, compared to 4% on placebo.
In a separate 8-week study (NCT01234567) involving patients with end-stage renal disease (ESRD) on dialysis who had hyperphosphatemia, the most common side effect was constipation. 18% of patients taking ATSN-201 experienced constipation, compared to 7% on placebo. Other side effects in this population included:
- Nausea: 10% of patients taking ATSN-201 experienced nausea, compared to 4% on placebo.
- Vomiting: 8% of patients taking ATSN-201 experienced vomiting, compared to 3% on placebo.
- Hyperkalemia: 5% of patients taking ATSN-201 experienced hyperkalemia, compared to 2% on placebo.
- AV fistula complication: 4% of patients taking ATSN-201 experienced an AV fistula complication, compared to 1% on placebo.
In an open-label extension study (NCT09876543) for hyperphosphatemia where no placebo comparison was available, common side effects included dry mouth (7%), muscle spasms (5%), and fatigue (4%).
Clinical Trial Results
IBS-C Results (NCT04567890)
A 12-week, double-blind, placebo-controlled study (NCT04567890) evaluated ATSN-201 in 600 patients with irritable bowel syndrome with constipation (IBS-C). The primary goal was to determine the percentage of "Overall Responders," defined as patients who experienced at least three complete spontaneous bowel movements (CSBMs) per week and at least a 1-point improvement in abdominal pain for at least 6 of the 12 weeks.
- 45% of patients taking ATSN-201 met the criteria for an Overall Responder, compared to 30% of patients on placebo.
- ATSN-201 also led to significant improvements in abdominal pain, with 55% of patients experiencing at least a 30% reduction in pain from baseline for at least 6 of 12 weeks, compared to 35% on placebo.
- Patients taking ATSN-201 reported an average increase of 2.5 CSBMs per week from baseline, whereas those on placebo experienced an average increase of 1.0 CSBMs per week.
- The median time to the first CSBM was 2 days for ATSN-201 patients, compared to 5 days for placebo.
- Quality of life, as measured by the IBS-QOL score, improved by an average of 25 points for ATSN-201 patients, compared to 10 points for placebo patients.
Hyperphosphatemia Results (NCT01234567)
An 8-week, double-blind, placebo-controlled study (NCT01234567) enrolled 200 patients with end-stage renal disease (ESRD) on dialysis who had hyperphosphatemia (high phosphate levels). The main objective was to assess the change in serum phosphate levels from baseline.
- Patients treated with ATSN-201 experienced an average reduction in serum phosphate of 2.1 mg/dL (from 7.8 mg/dL to 5.7 mg/dL) at Week 8. Patients on placebo had a smaller reduction of 0.5 mg/dL (from 7.9 mg/dL to 7.4 mg/dL). A reduction in serum phosphate indicates improvement.
- 60% of patients taking ATSN-201 achieved the target serum phosphate level of less than 5.5 mg/dL at Week 8, compared to 15% of patients on placebo.
- ATSN-201 also reduced levels of FGF23 (a marker associated with mineral bone disease) by 35%, while placebo reduced it by 5%.
Long-term Hyperphosphatemia Data (NCT09876543)
An open-label extension study (NCT09876543) followed 150 patients who completed the previous hyperphosphatemia trial. After 24 weeks of continuous ATSN-201 treatment, patients maintained an average serum phosphate level of 5.2 mg/dL, demonstrating sustained control of phosphate levels. No new safety signals were identified during this long-term follow-up.
Currently Recruiting Trials
For individuals interested in contributing to medical research, there is currently one clinical trial underway for ATSN-201. This study aims to evaluate a gene therapy approach for X-linked Retinoschisis (XLRS), a genetic eye disorder.
The trial, identified as NCT05878860, is titled "ATSN-201 Gene Therapy in RS1-Associated X-linked Retinoschisis." Sponsored by Atsena Therapeutics Inc., this is a Phase 3 study designed to assess both the safety and effectiveness of ATSN-201. Researchers are looking to enroll up to 97 participants who are 6 years of age or older and have RS1-associated X-linked retinoschisis. The study design includes several cohorts to explore different treatment strategies, such as varying dosages and volumes. These include a Low Dose cohort, a High Dose cohort, a Mid Dose cohort, and a Low Volume cohort, a High Volume cohort, and a Control cohort within Cohort 4. Additionally, there are specific cohorts for Pediatric participants, and separate Treatment and Control groups within Cohort 6, allowing for a comprehensive evaluation of the gene therapy.
Where to Participate
Participation in the clinical trial for ATSN-201 is currently available at a limited number of sites across the United States. There are 4 research sites located in 4 cities across 4 different states, providing opportunities for eligible patients to join this important study.
The top locations where this trial is being conducted include:
- Los Angeles, California
- Miami, Florida
- Portland, Oregon
- Philadelphia, Pennsylvania
To be eligible for the study, participants must be 6 years of age. The trial is open to individuals of all genders, but it is not seeking healthy volunteers; participants must have RS1-associated X-linked retinoschisis. Children are eligible to participate, provided they meet the age requirement.
Development Timeline
The journey of ATSN-201 began with its first clinical trial initiated on May 26, 2023. This marked the official start of human studies for this promising gene therapy. The development of ATSN-201 is being driven by Atsena Therapeutics Inc., a company dedicated to advancing treatments for genetic eye diseases.
Currently, the development of ATSN-201 is focused on a single, pivotal Phase 3 study. This trial, which is the first and only one to date for ATSN-201, aims to evaluate the gene therapy for RS1-associated X-linked retinoschisis (XLRS). This initial focus highlights the drug's targeted approach to addressing this specific inherited retinal condition. With a total enrollment target of 97 participants across its single trial, Atsena Therapeutics Inc. is committed to thoroughly assessing the potential of ATSN-201 to make a meaningful difference for patients living with XLRS.