Neurotech Pharmaceuticals, Inc. announced the FDA has approved its allogeneic encapsulated cell-based gene therapy for the treatment of macular telangiectasia type 2 (MacTel): ENCELTO (revakinagenetaroretcel-lwey).
Important to note: This marks a historic moment, as ENCELTO is now the first-ever FDA-approved treatment for this neurodegenerative retinal disease.
First, a refresh of this company.
The clinical-stage biotechnology company has one main purpose: Developing sustained drug deliveries for chronic retinal diseases.
Its current target: MacTel, a rare, age-related, and bilateral neurodegenerative retinal disease that causes a gradual deterioration of central vision in adults over the age of 40.
What’s the basis for these sustained drug deliveries?
That would be the Encapsulated Cell Therapy (ECT) platform, Neurotech’s core platform technology.
About this platform: Referred to by the company as a “unique and versatile platform,” the ETC is designed to continuously produce and deliver targeted therapies (singularly and in combination) to the back of the eye for the long term.
- Its foundation: Is the customizable NTC-200 cell line, which can be genetically engineered to produce “clinically relevant levels of therapeutic protein.”
To note: NTC-200 cells exist in low oxygen and nutrient conditions and can be genetically manipulated under "stringent selection methods.”
Explain how the platform targets disease.
Within the ECT is a small, semi-permeable capsule that contains proprietary allogeneic retinal pigment epithelium (RPE) cells genetically altered to produce specific therapeutic proteins for targeted disease treatments.
For an overview on how this delivery process works, click here.
And how does this compare to standard injections?
Ideally, the platform is intended to potentially “mitigate the risks associated with repeated intraocular injections or drugs”and bypass restrictions associated with “conventional allogeneic cellular transplantation,” according to the company.
The key difference: The platform controls the drug dosage delivered to the eye (at a constant rate, keep in mind) over a longer duration of time (think: years) to target chronic ocular diseases.
Got it. Now talk about this newly-approved ECT.
Originally dubbed NCT-501, ENCELTO is an ocular implant that depends on the ECT platform to deliver therapeutic doses of ciliary neurotrophic factor (CNTF) into the retina to slow disease progression.
- CNTF debrief: This cytokine is naturally produced by neurons and Müller cells, and is known to have a neuroprotective effect on retinal degeneration—specifically protecting against photoreceptor loss in MacTel.
Tell us the basics of it.
Its indication and usage: For the treatment of adults with MacTel.
Administration guidelines: Per ENCELTO’s prescription information (PI), it is intended for surgical intravitreal implantation only under aseptic conditions—and only by an ophthalmologist.
- Recommended dosage: One single-dose implant per affected eye containing 200,000 to 440,000 allogeneic RPE cells expressing recombinant human CNTF (rhCNTF).
And what kind of clinical data supported the FDA’s decision?
Promising findings from two randomized phase 3 trials evaluating ENCELTO’s performance among over 200 patients diagnosed with MacTel.
The crux of that data: A statistical significance was demonstrated for the primary endpoint—rate of change in ellipsoid zone area loss from baseline to 24 months—with the implant determined to be safe, durable, and well-tolerated in both studies:
- 56.4% rate of reduction in the first trial (p<0.0001)
- 29.2% rate of reduction in second trial (p=0.021)
Any contradictions or warnings associated with its use?
A few were noted:
Contraindications: ocular or periocular infections; known hypersensitivity to endothelial serum-free media (Endo-SFM).
Warnings and precautions extend to the implantation’s association with:
- Severe vision loss
- Infectious endophthalmitis
- Retinal tears and/or detachment
- Vitreous hemorrhage (see here for details on this)
- Implant extrusion
- Cataract formation
- Suture-related complications
- Delayed dark adaptation
How about known adverse events?
Based on its clinical data, the most common adverse events (AEs) occurred in ≥2% of patients.
Among them: conjunctival hemorrhage; eye pain; miosis; ocular discomfort; blurred vision; dry eye; vitreous floaters; and severe vision loss. See here for a complete list.