AbbVie and Ripple Therapeutics have entered into a collaboration and option-to-license agreement to develop an IC implant for reducing intraocular pressure (IOP) in patients diagnosed with open-angle glaucoma (OAG) or ocular hypertension (OHT).
I’m familiar with AbbVie, but not Ripple ...
Headquartered in Toronto, Ontario, the privately held, clinical-stage pharmaceutical company was founded in 2019 with a focus on improving ophthalmic therapeutics via controlled, sustained drug delivery.
Its pipeline of glaucoma- and retina-based investigational therapeutics includes implantable prodrugs for the following conditions:
- Diabetic macular edema (DME); retinal vein occlusion (RVO)
- Non-infectious uveitis (NIU); cystoid macular edema (CME); and retinitis pigmentosa (RP)
- Wet age-related macular degeneration (AMD)
- OAG; OHT
- Glaucoma neuroprotection
And the basis for its science?
The company’s patented technology platform uses chemical engineering to transform drugs into “implantable prodrug materials” that undergo surface erosion to release an active drug.
- These drugs: Dubbed “Epidel prodrugs,” these feature properties that enable them to be processed into standalone drug delivery implants—such as intravitreal (IVT) implants and micro-nanoparticles—or as medical device coatings.
Explain how this works.
By way of “surface erosion,” these prodrugs dissolve from the Epidel implant surface in a “highly predictable manner” to give “zero order release kinetics.”
- Specifically: These are highly customizable drugs, as the dose is determined by the implant’s surface area, while the dose duration is dictated by the implant’s diameter.
And what’s key with this?
Importantly: This controlled release is done without the use of polymers or excipients.
- Because of this: Once none of the drug is left, the “implant is gone with no pro-inflammatory degradation products”—enabling repeat dosing.
The result is “an ability to finely tune pharmacokinetics to meet the needs of a target indication with precision control of drug dosing without the bulk added by a polymer,” according to the company.
So how will the partnership utilize Ripple’s technology?
Via the agreement, the companies will be developing one of Ripple’s intracameral (IC) implants (RTC-620 … more on that in a moment) for the indication of lowering IOP in OAG and OHT patients.
Specifically: Ripple will head up the preclinical development of RTC-620, while AbbVie will lead the implant’s clinical and commercialization activities.
I have to ask … any financial details disclosed?
The companies reported that Ripple will receive an upfront payment of $21.8 million from AbbVie, with eligibility to receive up to $290 million in aggregate options fees and milestones (plus tiered royalties on net sales).
Gotcha. Now what do we know about this implant?
The next-generation, fully biodegradable, sustained-release drug delivery IC implant (that’s a mouthful!) is designed to provide an intravitreal (IVT) delivery of bimatoprost acid.
Clinical data evaluating its ocular tolerability and IOP-lowering capabilities when used in normotensive beagle dogs was presented earlier this year during the Association for Research in Vision and Ophthalmology (ARVO) annual meeting.
What were the goals of this research?
First: The implant (0.2 x 1.5 mm) was administered into the left eye (OS) of five subjects (with 30 µg bimatoprost acid) on Day 1 followed by a repeat-dose at Month 4.
- Note: An IC sham implant was administered in the right eye (OD) with the same dosing.
Researchers had two primary objectives:
- IOP-lowering with the RTC-620 IC implant
- Corneal safety via specular microscopy post-repeat dosing
And that data?
The findings included that IOP-lowering and pupil constriction were maintained prior to and following the second administration of the RTC-620 IC implant.
- Translating canine findings to humans: The investigators determined that a 10% IOP-lowering in canines would equate to ~30% in human patients.
Let’s talk surface erosion.
Based on the data, the implants successfully settled and remained “in inferior iridocorneal angle following IC administration,” with no tissue response to the RTC-620 implant noted in the angle.
- Further: The research determined that “small implant size and surface erosion mechanism [enabled] multiple implants to safely reside in inferior angle.”
Were corneal endothelial cell density or thickness impacted?
The company reported that neither was impacted following the single or repeat dosing of the RTC-620 implant.
- In fact: For corneal endothelial cell density (CECD) all eyes demonstrated a <15% difference from initial assessment at all timepoints.
Additionally: When evaluated via optical coherence tomography (OCT), no differences were noted between the central or inferior corneal thickness of RTC-620 implant-treated eyes vs sham-treated eyes.
And in all?
The implant’s strong corneal safety profile was evidenced by:
- No corneal observations on ocular exams
- No change in corneal thickness vs sham eyes
- No change in CECD after repeat dosing
As a bonus: The implant demonstrated a favorable ocular tolerability profile.
Sounds promising … so when will it be tested in humans?
Per the researchers, the next clinical step for this implant involves investigational new drug (IND)-enabling studies to support a future first-in-human (FIH) study with repeat dosing.