Genentech, Inc., a member of the Roche Group, has announced plans to bring back the first sustained-release drug delivery system to the U.S. market for the treatment of wet age-related macular degeneration (AMD).
The drug delivery device: SUSVIMO, an intravitreal ocular implant of 100 mg/mL ranibizumab injection, originally recalled in 2022. It was formerly referred to as the Port Delivery System (PDS).
I’m going to need some background on this.
First things first: SUSVIMO (ranibizumab injection) is a drug implant indicated for the treatment of wet AMD in patients who previously responded to at least two injections of a vascular endothelial growth factor (VEGF) inhibitor administered intravitreally.
- Its clinical status: The injection was originally approved by the FDA in October 2021 to be used with its accompanying ocular implant
And its purpose?
The device is designed to provide ongoing delivery of a customized formulation of ranibizumab (the active ingredient in the company’s LUCENTIS) via a proprietary drug delivery system during an outpatient procedure for the initial fill and implantation.
The recommended dosage: 2 mg (0.02 mL of 100 mg/mL solution in a single-dose vial) continuously delivered via the implant, with refills every 24 weeks (an estimated 6 months)
- Note: If clinically necessary, supplemental treatment of 0.5 mg intravitreal ranibizumab injection may also be administered in the affected eye.
- See here for SUSVIMO’s complete prescribing information (PI).
And how does it compare to other wet AMD treatments?
SUSVIMO requires only two refills per year—translating to less frequent dosings vs other wet AMD treatments like its own VABYSMO (faricimab-svoa) as well as EYLEA (aflibercept injection; Regeneron, Inc.).
Those schedules, as per their respective PIs:
- VABYSMO for wet AMD:
- 6 mg (0.05 mL of 120 mg/mL solution) administered via intravitreal injection every 4 weeks (approximately every 28 ± 7 days, monthly) for the first four doses
- This is followed by:
- Optical coherence tomography (and visual acuity evaluations 8 and 12 weeks later to determine whether to intravitreally administer a 6 mg dose on one of the following three regimens:
- Weeks 28 and 44
- Weeks 24, 36 and 48
- Weeks 20, 28, 36 and 44
- EYLEA for wet AMD:
- 2 mg (0.05 mL of 40 mg/mL solution) biosimilar is intended to be intravitreally administered every 8 weeks following an initial monthly dose for 3 months.
So why was it discontinued?
In October 2022, Genentech issued a voluntary recall of SUSVIMO that included the initial fill kit.
- Important to note: This recall did not include the SUSVIMO (ranibizumab injection) 100 mg/mL nor its refill needle.
The reason for this recall: The company stated that it identified “a need for additional testing of the commercial implant supply” during an investigation into septum dislodgement cases in the drug delivery system with ranibizumab phase 3 clinical trial program.
- This phase 3 trial was the basis for the implant’s FDA approval.
Explain what happened during the phase 3 program.
Genentech reported a damage to where the septum dislodged into the implant body—a manufacturing problem and a notable concern listed under the product’s Warnings and Precautions in its PI.
Refresh: Septum dislodgement occurs when a small part of he Susvimo implant (ie: the septum) becomes dislodged (removed) and falls into the implant body.
And what would a septum dislodgement mean?
According to the PI, this would necessitate the need for a physician to monitor its occurrence by examining the implant both prior to and after each refill-exchange procedure.
How many cases of this were reported?
By August 2022, a total of 33 cases of septum dislodgement in an estimated 1,419 patients with implants,
Keep in mind: This was less than 1 year following SUSVIMO’s October 2021 FDA approval.
Yikes. So did they perform that additional testing?
Indeed they did. The testing on the company’s commercial supply of SUSVIMO involved “repeatedly puncturing SUSVIMO implants with a needle” in order to ascertain the implant’s septum performance over a longer period of time via multiple refills.
- Those findings: Not all implants performed to the company’s standards—leading to Genentech’s decision to pause production of all new implants for the time being in order to ensure patient safety.
Alrighty, so why bring this implant back to the market now?
Genentech stated that it has since “updated the SUSVIMO implant and refill needle, and testing confirmed that they now meet those performance standards.”
Even further, the company also noted that "component level" updates have been made to the ocular implant and refill needle.
This is exciting! So when will it be available?
Per the company, SUSVIMO is expected to be reintroduced in the “coming weeks” as another treatment option for wet AMD patients.
Stay tuned for more details!
Editor's note: This article was updated on July 10, 2024.