TRS01 has the potential to be the first-line treatment option for non-infectious uveitis and specifically uveitic glaucoma, according to the company.
Tarsier Pharma Ltd announced the successful outcome of a Type C meeting with the FDA, supporting the advancement of TRS01 eye drop formulation for the treatment of noninfectious uveitis into a registrational program based on the recently completed TRS4Vision trial.
Zohar Milman, MSc chief operational officer of Tarsier, said in a news release the company was pleased to have FDA agreement on the primary and key secondary endpoints for the registrational program of TRS01 which it believes has the potential to be first-in-class first-line treatment for noninfectious uveitis and specifically in uveitic glaucoma,
"We are grateful for the FDA's support and guidance and look forward to continue the professional discussions as we advance TRS01 development,” Milman said in the news release.
According to the company, the Type C meeting was supported by results from the previously completed TRS4Vision trial – a randomly assigned, double-masked, active-controlled Phase 3 trial that was designed to evaluate the efficacy and safety of TRS01 eye drop formulation in noninfectious uveitis patients including uveitic glaucoma patients.
In the TRS4Vision trial, TRS01 was found to be active in clearing inflammation, reducing ocular pain and exhibited a compelling risk/benefit profile, minimizing the concerns of IOP increase during the course of treatment.1
Moreover, the company noted its upcoming trial is intended to replicate the TRS4Vision trial, with revised endpoints in accordance with FDA discussions. The revised endpoints are specifically designed to emphasize the risk/benefit profile of TRS01. The primary endpoint chosen has already attained statistical significance in the TRS4Vision trial, with a p-value <0.01.1
Quan Dong Nguyen, MD, MSc, FAAO, FARVO, FASRS, professor of Ophthalmology, Medicine, and Pediatrics at the Byers Eye Institute, Stanford University School of Medicine, and who is an international leader in Uveitis and Ocular Inflammatory Diseases and the president of the International Ocular Inflammation Society (IOIS), said the positive results demonstrate TRS01 could be a treatment option for patients.
"The results from the TRS4Vision trial demonstrates that TRS01 has a positive risk/benefit profile for the most vulnerable eyes that already reached the stage of uveitic glaucoma," Nguyen said in the news release. "There is growing evidence on the substantial risk of increased IOP in uveitis and a clear understanding that we need a steroid-free first line treatment for the active phase of anterior non-infectious uveitis. The data thus far support that the TRS01 profile has the potential to slow or prevent clinically meaningful progression of glaucoma in noninfectious uveitis and serve as first-line treatment in uveitic glaucoma," said Professor Nguyen.
Dazdotuftide (formerly known as TRS) is a first-in-class drug with a new and unique mechanism of action, for the treatment of ocular blinding diseases of back- and front- of the eye. Dazdotuftide is a bio-inspired novel proprietary technology platform, based on a New Chemical Entity (NCE) with a disruptive mechanism of action. Dazdotuftide was found to modulate macrophages from inflammatory macrophages (M1) to IL-10 secreting ant-inflammatory macrophages (M2).1
According to the company, it is developing dazdotuftide as an eye drop formulation (TRS01) for front-of-the-eye indications and as a slow-release biodegradable intravitreal injection (TRS02) targeting back-of-the-eye blinding indications with an underlying inflammatory pathology, such as diabetic macular edema, non-proliferative diabetic retinopathy, and others.
Due to dazdotuftide's unique mechanism of action of immunomodulation, we believe it has the potential to treat these debilitating diseases with a sustained effect and minimal risk of IOP elevation.
The company sought to meet with the FDA after its TRS4VISION trial failed to meet its primary endpoint.
In a news release in August, the company noted its primary endpoint of total resolution of inflammation in week four was not met in the Phase III study of TRS01 eyedrops, a 1% ophthalmic solution. The company said the results show a blend of safety and inflammation resolution that is promising in the treatment of non-infectious uveitis and specifically in uveitic glaucoma.2
The company noted in its news release at the time that according to post hoc analysis and based on the findings, the benefit-risk profile of TRS01 was judged to be positive regarding the total clinical impact on patients' lives.
Although the steroid active control was effective at the end of the treatment period, the inflammation resolution was transient, with a 2-fold higher rate of rebound (relapse of inflammation within 2 weeks) compared to the TRS01 treatment arm and up to 6-fold higher rate of rebound compared to TRS01 treatment arm in a pre-specified subgroup.
A 2.6-fold higher rate in the steroid active control arm presented a clinically meaningful IOP elevation after only four weeks of treatment compared to the TRS01 arm. This steroid induced IOP elevation is a known side effect of steroids and the key reason why uveitic glaucoma patients should not be treated with steroids.
A significantly higher proportion of patients that had a total resolution of inflammation with TRS01 compared to the steroid active control arm, maintained an intraocular pressure lower than 16 mmHg. According to the MUST trial an IOP measure lower than or equal to 16mmHg substantially reduces the risk of developing glaucoma which is critical for these patients.
Based on the totality of the data thus far from the clinical investigations of TRS01 it was found that TRS01-1% has a favorable safety and tolerability profile in noninfectious uveitis.
Overall, the TRS4Vision data demonstrated the potential of TRS01 ophthalmic solution to deliver a risk-benefit product profile of sustained resolution of inflammation and stable IOP.2
Daphne Haim-Langford, PhD, president and CEO of Tarsier, said at the time the company remained excited about these results.
“We are grateful to the many patients, caregivers, and physicians who have enabled the development of TRS01 and are encouraged by the opportunity TRS01 may have in meaningfully improving quality of lives of patients in need,” she said in the news release. “Based on the TRS4Vision trial results, we plan to engage with regulators to determine the optimal path forward to bring TRS01 to patients as expeditiously as possible."