One-year trial results show efficacy, safety of longer-interval faricimab for wet AMD, DME
One-year results of four phase 3 trials of faricimab showed safety and efficacy comparable to aflibercept in the treatment of wet age-related macular degeneration and diabetic macular edema, with potentially longer treatment intervals.
Across all four pivotal studies, about 50% of patients treated with faricimab (Genentech) were able to achieve a treatment interval of 16 weeks, and more than 70% could be treated every 12 weeks or longer.
According to the authors of the studies, both published in The Lancet, these results represent a major step forward, potentially heralding an important shift toward multitargeted treatment strategies with extended dosing intervals and reduced treatment burden.
Faricimab is a bispecific antibody targeting two distinct pathways involved in the pathophysiology of wet AMD and DME: VEGF and angiopoietin-2 (Ang-2), a ligand that plays a key role in vascular destabilization and inflammation. This dual pathway of inhibition was evaluated in the parallel TENAYA and LUCERNE trials for wet AMD and YOSEMITE and RHINE for DME. All four studies, which enrolled more than 3,000 patients, met their primary endpoints, showing that faricimab administered at intervals up to 16 weeks achieved noninferior vision outcomes compared with aflibercept at fixed-dosing intervals of 8 weeks.
The wet AMD trials
In TENAYA and LUCERNE, after the first four monthly doses, 1,329 patients across 271 clinical sites worldwide were randomly assigned to intravitreal faricimab up to every 16 weeks or aflibercept every 8 weeks. The extension, maintenance or shortening of the intervals in the faricimab group was based on disease activity assessments at weeks 20 and 24.
“Both trials met the primary endpoint of noninferiority in mean change from baseline in BCVA with faricimab up to every 16 weeks compared with aflibercept every 8 weeks,” Arshad M. Khanani, MD, MA, TENAYA and LUCERNE study investigator, said in an interview with Healio/OSN.
In TENAYA, mean gains in best corrected visual acuity at primary endpoint visits were 5.8 letters in the faricimab group and 5.1 letters in the aflibercept group. In LUCERNE, vision gains were 6.6 letters in both the faricimab and aflibercept groups. Anatomical outcomes were consistent with vision gains, with faricimab resulting in a meaningful and comparable reduction in central subfield thickness (CST).
The durability of faricimab in patients with wet AMD was also impressive, according to Khanani. In the faricimab arm, approximately 80% of patients achieved a 12- or 16-week treatment interval and approximately 45% achieved a 16-week interval in the first year after the loading doses.
“Treatment burden in patients with nAMD continues to be a major issue in clinical practice, resulting in poor long-term vision gains. Faricimab has the potential to significantly decrease treatment burden for the majority of our patients with nAMD and hopefully improve long-term vision outcomes,” he said.
The DME trials
“Primary results from YOSEMITE and RHINE support the hypothesis that dual Ang-2 and VEGF-A inhibition with faricimab might promote vascular stability beyond current anti-VEGF therapies for DME,” Charles C. Wykoff, MD, PhD, YOSEMITE and RHINE study investigator, told Healio/OSN.
In both studies, after the loading phase, 940 patients with DME across 353 sites worldwide were randomly assigned to receive faricimab at fixed intervals every 8 weeks, faricimab at personalized treatment intervals (PTI) up to 16 weeks or aflibercept every 8 weeks.
A mean gain of 10.7 ETDRS letters in the faricimab 8-week group and 11.6 ETDRS letters in the faricimab PTI group vs. 10.9 ETDRS letters in the aflibercept 8-week group was achieved in YOSEMITE. In RHINE, mean gain was 11.8, 10.8 and 10.3 ETDRS letters in the three groups, respectively. Reductions in CST over 1 year consistently favored faricimab over aflibercept.
More than 70% of patients in the PTI groups of both studies maintained an interval of 12 weeks or longer up to 1 year, and more than 50% achieved dosing every 16 weeks.
“Data from the PTI arm, with adjustable dosing up to every 16 weeks, have demonstrated the potential for individualized faricimab therapy to maintain vision gains and improve anatomical outcomes with extended dosing intervals for most patients, which might help to reduce treatment burden and close the patient outcome gap between clinical trials and current clinical practice,” Wykoff said.
The outcomes of all four studies offer hope to the many patients with retinal pathologies who need frequent monitoring and treatment and are often unable to attend regular appointments.
“More durable pharmacotherapies are needed in the management of exudative retinal disease such as nAMD and DME. The introduction of faricimab offers the hope of being able to meaningfully increase the interval between treatments,” Wykoff said.
Safety and long-term outcomes
Looking at safety signals is important for a new molecule, and faricimab was generally well tolerated in all studies, with a favorable benefit-risk profile, Khanani said. Ocular adverse events were consistent with those expected with intravitreal anti-VEGF injections in patients with wet AMD and DME and were mostly mild or moderate in severity. Rates of intraocular inflammation were low but numerically higher in the faricimab groups compared with aflibercept. In the majority of cases, however, they were resolved or resolving by the end of the first study year.
TENAYA and LUCERNE, as well as YOSEMITE and RHINE, are ongoing trials, and 2-year outcomes, as well as the AVONELLE-X and RHONE-X extension trials, will provide further long-term data.
“There is always more to learn. After the 2-year safety and efficacy data from both phase 3 DME trials are evaluated, outcomes from the ongoing long-term extension study will be important to evaluate closely for evidence of benefit of Ang-2 inhibition, particularly in the ability to stabilize the disease state in DR with extended dosing out to every 16 weeks,” Wykoff said.
“Long-term data will confirm the efficacy, safety, durability and possible impact of Ang-2 inhibition with faricimab in disease modification in patients with nAMD,” Khanani said.
Of note, the trials were conducted during the COVID-19 pandemic, with a potential impact on participants, trial conduct and data collection at various times in different parts of the world. In response, strategies were implemented to ensure safety and continuity of care, and supplemental analyses were done to test the robustness of the results.
- Heier JS, et al. Lancet. 2022;doi:10.1016/S0140-6736(22)00010-1.
- The Lancet publishes studies showing Genentech’s faricimab improved and maintained vision in two leading causes of vision loss, extending time between treatments up to four months. https://www.gene.com/media/press-releases/14941/2022-01-24/the-lancet-publishes-studies-showing-gen. Published Jan. 24,2022.
- Wykoff CC, et al. Lancet. 2022;doi:10.1016/S0140-6736(22)00018-6.
For more information:
Arshad M. Khanani, MD, MA, can be reached at Sierra Eye Associates, 950 Ryland St., Reno, NV 89502; email: firstname.lastname@example.org.
Charles C. Wykoff, MD, PhD, can be reached at Retina Consultants of Texas, Retina Consultants of America, 4460 Bissonnet St. #200, Houston, TX 77401; email: email@example.com.