Mere weeks after Genentech, Inc., a member of the Roche Group, announced plans to reintroduce SUSVIMO, its first sustained-release drug delivery system, for wet age-related macular degeneration (AMD), the company is reporting new phase 3 data supporting its efficacy for two diabetic eye diseases.
Let’s start with a refresh on SUSVIMO.
Formerly referred to as the Port Delivery System, SUSVIMO (ranibizumab injection) is an intravitreal (IV) ocular implant of 100 mg/mL ranibizumab injection 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.
- Note: The injection was originally approved by the FDA in October 2021 to be used with its accompanying ocular implant and later voluntarily recalled in 2022 (more on that in a moment).
So how does it work?
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.
And its dosage?
Per SUSVIMO’s prescribing information (PI), 2 mg (0.02 mL of 100 mg/mL solution in a single-dose vial) is intended to be continuously delivered via the implant, with refills every 24 weeks (an estimated 6 months).
Clinical note: Supplemental treatment of 0.5 mg IV ranibizumab injection may also be administered in the affected eye, as needed.
Real quick: Dive into its discontinuation (and reintroduction) in the US.
Back in 2022, the company issued a voluntary recall of SUSVIMO that included its initial fill kit—not, importantly, the SUSVIMO (ranibizumab injection) 100 mg/mL or its refill needle.
The reason: Cases of septum dislodgement were identified in its phase 3 clinical program that required additional testing.
Fast forward to earlier this month: Genentech reported it has since updated the SUSVIMO implant and refill needle to meet performance standards. Get the full details in our coverage.
Alrighty, now let’s talk about these clinical trials.
The 2-year data is from two multicenter, randomized, U.S.-based phase 3 trials evaluating SUSVIMO for both DME and DR:
- Pagoda (NCT04108156)
- n = 634 (aged 18+)
- Diagnosed with diabetes mellitus (type 1 or 2)
- Setup:
- Participants randomized 3:2 to receive either:
- SUSVIMO 100 mg/mL refilled every 6 months vs
- Note: Four loading doses of IV ranibizumab administered before SUSVIMO implantation at Week 16
- Monthly ranibizumab 0.5 mg IV injections
- SUSVIMO 100 mg/mL refilled every 6 months vs
- Participants randomized 3:2 to receive either:
- Following primary analysis: Patients randomized to IV injections received SUSVIMO (refills administered every 24 weeks)
- n = 634 (aged 18+)
- Pavilion (NCT04503551)
- n = 174 (aged 18+)
- Diagnosed with diabetes mellitus (type 1 or 2)
- Setup:
- Participants randomized 5:3 to receive either:
- SUSVIMO 100 mg/mL refilled every 9 months vs
- Note: Two loading doses of IV ranibizumab administered before SUSVIMO implantation at Week 4
- SUSVIMO 100 mg/mL under monthly observation
- SUSVIMO 100 mg/mL refilled every 9 months vs
- Participants randomized 5:3 to receive either:
- Following primary analysis: Patients initially in the clinical observation arm were administered two ranibizumab loading doses prior to SUSVIMO implantation at Week 64
- n = 174 (aged 18+)
And the primary endpoints for each?
For Pagoda: Change in best-corrected visual acuity (BCVA) from baseline at the average of Weeks 60 and 64, respectively.
For Pavilion: Number of patients with at least a two-step improvement from baseline on the Early Treatment DR Study-DR Scale (ETDRS-DRS) at Week 22.
Before we get to 2-year data, any 1-year results to know about?
Indeed. Genentech reported the following:
- For Pagoda: Patients with 6-month refills of SUSVIMO achieved non-inferiority visual acuity (VA) gains vs those receiving monthly 0.5 mg ranibizumab IV injections
- Further: 95% of SUSVIMO patients didn’t need additional supplemental injections through Week 64
- For Pavilion: Patients with 9-month refills of SUSVIMO achieved “superior improvements on the DRSS vs those under monthly clinical observation
- Plus: No SUSVIMO patients required additional supplemental injections through 52 weeks (vs 60% of control-arm patients)
Can you go into specifics on BCVA performance?
For the Pavilion study, yes! Data from that trial (Week 36 through Week 52) reported during the 2023 Angiogenesis annual meeting last fall found that SUSVIMO maintained BCVA following the expected transient postsurgical drop in vision (at Week 8).
- The numbers: SUSVIMO-treated patients achieved an average of +1.4-letter increase vs -2.6-letter decrease for control patients
Sounds promising … now this new data.
Per Genentech, the 2-year results build on 1-year data from both studies, with SUSVIMO “demonstrating sustained efficacy over 2 years and safety consistent with the known safety profile” of the implant for DME and DR patients.
The findings were presented over the weekend during the American Society of Retina Specialists (ASRS) 2024 Annual Meeting in Stockholm, Sweden.
Give me some numbers from Pagoda.
Patients with 6-month SUSVIMO refills (through to an estimated 2-year period; 112 weeks) “continued to maintain improvements in vision gains seen at 1 year (9.8 eye chart letters).”
Plus, similar to 1-year data, 95% of these patients didn’t need supplemental injections.
- Also: Sustained improvements were noted in central subfield thickness (CST) through Week 112, with no new safety signals or cases of endophthalmitis reported through 1 year
Now Pavilion data.
Patients with 9-month SUSVIMO refills (through to an estimated 2-year period; 100 weeks) “maintained DRSS improvements” previously noted at 1 year.
- Specifically:
- 90% of these patients achieved a 2-step or greater improvement on the DRSS from pre-implant baseline
- 98% (approximately) of these patients also did not need supplemental injections
- No new safety signals or endophthalmitis cases were reported up to 1 year (with the endophthalmitis rate at 0.8% through Week 100)
Nice! Anything else to report?
Yes, actually … the FDA has also accepted Genentech’s supplemental Biologics License Application (sBLA) for SUSVIMO to treat DME and DR.
Note: This acceptance was based on the company’s previously-reported 1-year data from the Pagoda and Pavilion trials (which we summarized above).
Keep in mind: SUSVIMO is already approved for wet AMD in the U.S.
So what’s next?
Stay tuned for an announcement from Genentech on when the SUSVIMO implant (for wet AMD) will be available in the U.S.