Ocular Therapeutix updates on clinical developments and future plans for Axpaxli

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Article

The company highlighted successful enrollment in the SOL-1 Phase 3 trial for wet AMD, plans for a new repeat dosing study (SOL-R), and positive 48-week data from the Phase 1 HELIOS study for NPDR

(Image Credit: AdobeStock/ximich_natali)

(Image Credit: AdobeStock/ximich_natali)

Ocular Therapeutix Inc hosted an Investor Day where it highlighted clinical development progress with Axpaxli for wet age-related macular degeneration (wet AMD) and non-proliferative diabetic retinopathy (NPDR) and updated its corporate strategy.

Pravin U. Dugel, MD, CEO, president and executive chairman of Ocular Therapeutix, noted the company has put together a team of leaders in retina in efforts to become a leader in retinal care.

“We are already seeing the positive impact of these efforts, based on exceptional enrollment in the pivotal SOL-1 Axpaxli study for wet AMD, coupled with plans for a new SOL-R repeat dosing study and the report of positive 48-week topline data from the Phase 1 HELIOS NPDR study,” he said in a news release.“Our transformation into a retina-focused company is built on three pillars: convincing data from three clinical studies with Axpaxli, de-risking the regulatory pathway in wet AMD, and a focus on expansive, retinal vascular disease markets. We are more confident today than ever before that Axpaxli has demonstrated monotherapy activity, with potential best-in-class durability and a favorable safety profile that is well positioned to disrupt today’s treatment paradigm which includes frequent, burdensome regimens.”

Axpaxli is an investigational bioresorbable, hydrogel implant incorporating axitinib, a small molecule, multi-target, tyrosine kinase inhibitor with anti-angiogenic properties, being evaluated for the treatment of wet AMD, DR, and other retinal diseases.1

During its Investor Day, the company noted the SOL-1 study has 60 study sites active and 151 subjects enrolled in various stages of loading and randomization as of June 7, 2024. The study is being conducted under a Special Protocol Assessment (SPA) with the US FDA. The Company intends to randomize 300 treatment naïve patients in the SOL-1 study, comparing a single implant (450µg) to a single aflibercept injection (2mg) after all patients have received two loading doses of aflibercept.

The pivotal Phase 3 SOL-1 trial is designed to evaluate the safety and efficacy of the investigational bioresorbable, hydrogel implantin a multi-center, double-masked, randomized (1:1), parallel group study that involves sites primarily located in the United States. The trial is intended to randomize approximately 300 evaluable treatment-naïve patients with a diagnosis of wet AMD in the study eye.

The superiority study begins with an 8-week loading segment, a 9-month treatment segment followed by a safety follow-up. During the loading segment, subjects who have 20/80 vision or better and who satisfy other enrollment criteria receive two doses of aflibercept (at week -8 and week -4). Subjects that achieve visual acuity of 20/20 at Day 1 or gain at least 10 early treatment diabetic retinopathy (ETDRS) letters at Day 1 are then randomized to receive a single dose of Axpaxli or a single dose of aflibercept and assessed monthly for the entire study. The clinical trial protocol requires that, during the study, subjects in any arm meeting pre-specified rescue criteria will receive a supplemental dose of aflibercept.1

The primary endpoint of SOL-1 is the proportion of subjects who maintain visual acuity, defined as <15 ETDRS letters of BCVA loss, at Week 36.

Moreover, the company also noted during its presentation that it will initiate SOL-R Axpaxli repeat dosing study, currently in Phase 3 for wet AMD, to evaluate repeat dosing of Axpaxli (450µg) at 6 months (Q6M) compared to aflibercept (2mg) dosed every 8 weeks (Q8W) and a comparator arm dosed Q6M in 825 wet AMD patients.

The pivotal Phase 3 SOL-1 trial is designed to evaluate the safety and efficacy of Axpaxli in a multi-center, double-masked, randomized (1:1), parallel group study that involves sites primarily located in the United States. The trial is intended to randomize approximately 300 evaluable treatment-naïve patients with a diagnosis of wet AMD in the study eye.1

Dilsher S. Dhoot, MD, of California Retina Consultants noted in the news release that while SOL-1 enrollment has exceeded expectations, the research team shouldn’t have been surprised.

“We are recruiting treatment naïve wet AMD patients with good vision, the largest de novo patient population we see, and there is no competing clinical trial for these patients,” Dhoot said in the release. “Many patients know someone with wet AMD and understand how burdensome treatment is.”

Dhoot noted that when he talks to his patients about the SOL-1 study, they are excited about the potential durability of Axpaxli

“In addition, they like the study design because if they are randomized, they are guaranteed to receive an active agent, not a sham,” he said. “They find it comforting to know that I will see them monthly, at a minimum, and if the drug they are receiving appears to be losing strength, they can be rescued with aflibercept, as needed, for the remainder of the study.”

The company announced it plans to kick off SOL-R, a Phase 3 repeat dosing study in wet AMD to evaluate repeat dosing of Axpaxli (450µg) at 6 months (Q6M) compared to aflibercept (2mg) dosed every 8 weeks (Q8W) and a comparator arm dosed Q6M in 825 wet AMD patients.

This trial is designed for commercial impact and is being initiated at regulatory risk. Ocular has requested a Type C meeting to seek FDA guidance regarding the SOL-R protocol. Patients enrolled in SOL-R are initially expected to include patients that constitute loading or randomization failures from the SOL-1 study. The SOL-R protocol requires that all patients enrolled in SOL-R be enriched through multiple aflibercept (2mg) loading doses and monitored to ensure limited retinal fluid fluctuations prior to randomization. After the completion of enrollment and randomization of SOL-1, patients will be enrolled directly into the SOL-R study.1

Baruch D. Kuppermann, MD, PhD, chairman of the Department of Ophthalmology, and Director of the Gavin Herbert Eye Institute at the University of California, Irvine said in the news release he believes the start of the SOL-R study will be good news for patients and the retina community.

“Clearly, SOL-1 was designed as a regulatory study,” he said in the news release. “It is exactly what the FDA is asking for in their latest guidance documents and is being conducted under an SPA, which has become increasingly important in today’s regulatory landscape.”

Kuppermann explained that SOL-R is different because it is a large, ‘real-world’ repeat-dosing study designed to provide physicians with data on how we may ultimately use Axpaxli, if approved.

“I believe having the results of this study will be important for the retina community and so I am enthusiastic about the clinical trial,” he said in the release. “Further, I expect the SOL-R design feature to initially enroll patients who failed loading or randomization in SOL-1 to enhance enrollment in both studies by giving patients twice the opportunity to participate in a study.”

Moreover, the company provided 48-week data in its HELIOS study, which improves on previously reported 40-week data with all signals of diabetic retinopathy severity scale (DRSS) improvement coming from Axpaxli-treated patients while any vision threatening complications (VTCs) that developed were in sham-treated patients. The HELIOS study compares a single AXPAXLI implant (600µg) to a single sham injection with neither arm receiving a loading treatment. The Company plans to discuss these results with the FDA to determine a path forward for the development of Axpaxli in NPDR.1

The Phase 1 HELIOS trial is a multi-center, double-masked, randomized (2:1), parallel group study conducted in the U.S. The study was designed to evaluate the safety, tolerability, and efficacy of Axpaxli compared to a sham control in subjects with moderately severe to severe non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME).

The company also noted that in the HELIOS 48-week data, 23.1% of patients (N=3) demonstrated a ≥2-step DRSS improvement in the AXPAXLI arm at week 48 compared to 0% in the sham arm; an additional 23.1% of patients (N=3) demonstrated a 1-step DRSS improvement in the AXPAXLI arm compared to 0% in the sham arm.

None of the patients in the Axpaxli arm exhibited a worsening in DRSS by week 48 compared to 25% of patients (N=2) in the sham arm, and no patients in the Axpaxli arm developed proliferative diabetic retinopathy (PDR) or center-involved diabetic macular edema (CI-DME) by week 48 compared to 37.5% of patients (N=3) in the sham arm.

The company noted that, on average, patients in the Axpaxli arm showed improvement in central subfield thickness compared to the sham arm, which showed worsening over the 48-week follow up.

The company also noted that Axpaxli was generally well tolerated in the study and it did not lead to any reported incidence of intraocular inflammation, iritis, vitritis, or vasculitis.

Dhoot pointed out that after reviewing the expanded HELIOS Phase 1 data set in NPDR, he is even more comfortable that Axpaxli has the potential to be safe and effective, with durable activity in the back of the eye.

“The current approved anti-VEGF agents for DR necessitate frequent injections, and for that reason I have very few patients receiving treatment,” he said in the release. “In the HELIOS study, patients receiving Axpaxli sustained or improved DRSS to week 48 without the development of a single vision threatening complication, unlike patients in the sham control arm.”

Ultimately, Dhoot said it comes down to getting the best results for patients.

“In NPDR, I care about maintaining or improving my patients’ vision, and if I can do this with a 6 to 12-month treatment, I believe many of my patients would be very excited,” he concluded. “This is a differentiated result compared to other benchmark agents and it fortifies my confidence in the potential use of AXPAXLI in both wet AMD and NPDR.”

In April 2024, the company reported positive topline results from the Phase 1 HELIOS study (NCT0569541) evaluating its investigational bioresorbable, hydrogel implant (Axpaxli) versus a sham control in patients with moderately severe to severe non-proliferative diabetic retinopathy without diabetic macular edema (DME).

The company noted the results showed the investigational bioresorbable, hydrogel implant was generally well tolerated with no inflammation observed including no incidence of iritis, vitritis or vasculitis.2

The company also noted its cash runway extends into 2028, and it will include a prioritization of resources on the clinical development of Axpaxli for wet AMD.

Reference:
  1. Inc OT. Ocular TherapeutixTM Highlights Exceptional AXPAXLITM SOL-1 Enrollment and Plans for Repeat Dosing Study (SOL-R) in wet AMD at Investor Day, Along with Positive 48-week Data from HELIOS NPDR Study. GlobeNewswire News Room. Published June 13, 2024. Accessed June 14, 2024. https://www.globenewswire.com/news-release/2024/06/13/2898636/0/en/Ocular-Therapeutix-Highlights-Exceptional-AXPAXLI-SOL-1-Enrollment-and-Plans-for-Repeat-Dosing-Study-SOL-R-in-wet-AMD-at-Investor-Day-Along-with-Positive-48-week-Data-from-HELIOS-N.html
  2. ‌Ocular Therapeutix Announces Positive Topline Phase 1 Data for AXPAXLI in Diabetic Retinopathy | Ocular Therapeutix, Inc.. Ocular Therapeutix, Inc. Published 2024. Accessed April 18, 2024. https://investors.ocutx.com/news-releases/news-release-details/ocular-therapeutixtm-announces-positive-topline-phase-1-data
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