EyePoint Pharmaceuticals, Inc. announced the first patient dosing in its global phase 3 LUCIA clinical trial of DURAVYU (tyrosine kinase inhibitor; formerly known as EYP-1901) for the treatment of wet age-related macular degeneration (AMD).
This follows the company’s earlier news of the first patient dosing in its first global phase 3 trial: LUGANO.
First up: a DURAVYU refresh.
As a small-molecule, selective, and potent pan-vascular endothelial growth factor (VEGF) receptor inhibitor, DURAVYU (vorolanib intravitreal insert) is under clinical investigation for the treatment of retinal disease.
- How it works: The candidate incorporates a bioerodible formulation of EyePoint’s proprietary DURASERT E delivery technology with vorolanib (a tyrosine kinase inhibitor [TKI]).
Its proposed indications: delivered as a twice-yearly, single-dose IVT injection, DURAVYU is under clinical investigation for:
- Wet AMD and diabetic macular edema (DME)
- 6-month maintenance therapy
- Nonproliferative diabetic retinopathy (NPDR)
- 9-month maintenance therapy
Remind me about vorolanib.
Vorolanib is known to provide potent and selective pan-VEGF receptor inhibition by blocking downstream signaling of all three VEGF receptors.
In this case: EyePoint has noted that vorolanib also provides a potential new mechanism of action (MOA) for treating VEGF-mediated retinal diseases such as DME.
And circling back to that DURASERT tech?
This proprietary technology is a miniaturized, injectable, sustained-delivery system designed to provide a continuous and stable release of therapeutics within the eye over an extended period of time (think: weeks, months, and potentially even years).
- Its delivery mechanism: Via a standard, in-office, intravitreal (IVT) injection
Outside of vorolanib: The tech also works with other drugs as DURASERT E (bioerodible) and DURASERT (non-erodible).
Now, before we talk phase 3, what has phase 2 data demonstrated on DURAVYU?
Taking it back to December 2023: EyePoint released positive topline data from the phase 2 DAVIO 2 trial (NCT05381948).
The setup: Two doses of DURAVYU were evaluated in 150 wet AMD patients (aged 50+).
The data: DAVIO 2 met its primary endpoint, with both doses demonstrating a statistical non-inferiority change in (BCVA) compared to aflibercept control.
- Plus: DURAVYU demonstrated a favorable safety profile. See here for more details.
Alrighty, moving on to this LUCIA trial.
As a twin study to the phase 3 LUGANO trial (NCT06668064), this global, multicenter, prospective, randomized, double-masked, aflibercept-controlled study (NCT06683742) is evaluating the ability of DURAVYU to achieve similar visual outcomes as aflibercept while also reducing treatment burden in wet AMD patients.
- Participant info: 400 patients, including those previously treated and treatment-naïve
- Across 150+ clinical trial locations (240+ in total, including the LUGANO trial)
- The design: Patients randomized to two arms to receive either:
- 2.7 mg DURAVYU
- Administered every 6 months
- Starting at Month 2 (Week 8) of the trial following three loading doses of aflibercept
- Administered every 6 months
- 2 mg aflibercept on-label (control)
- Administered every 8 weeks (qw8; ie: 2 months)
- 2.7 mg DURAVYU
- Study duration: 1 year
And what’s under evaluation, exactly?
We’ll start with the primary endpoint: Difference in mean change in BCVA, as determined at Day 1 to Weeks 52 and 56 (blended) compared to aflibercept.
Secondary endpoints include:
- Safety
- Treatment burden reduction
- Percentage of supplement-free eyes
- Anatomical stability (determined via optical coherence tomography [OCT])
Now to the important question: What’s significant about this phase 3 program?
Both LUGANO and LUCIA are “the only sustained-release wet AMD phase 3 trials evaluating re-dosing in both trials,” according to Ramiro Ribeiro, MD, PhD, EyePoint chief medical officer.
He added that the data from both trials will offer key insights on the efficacy, durability, safety, and dosing flexibility of DURAVYU, as well as have the potential to “provide valuable insights on how DURAVYU could be used in ‘real-world’ practice.”
So when is data expected from this?
The company anticipates releasing topline data from the phase 3 program (both LUCIA and LUGANO) in 2026.