With neovascular age-related macular degeneration (nAMD) being the leading cause of severe, permanent vision loss in people over age 60, any addition to its treatment arsenal is eagerly welcome. One of the latest, faricimab (Vabysmo, Genentech), shows incredible promise for not only nAMD but diabetic macular edema (DME) as well.
As the first bispecific antibody, Vabysmo treats both diseases via intravitreal injection by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). After four trials involving over 3,000 participants, the United States Federal Drug Administration (FDA) approved Vabysmo in January 2022.
David Almeida, MD, MBA, PhD, a vitreoretinal eye surgeon at Erie Retinal Surgery, a retina-only private practice in Pennsylvania, director of clinical research at Erie Retina Research, and Chief Medical Editor of Eyes On Eyecare stated, “With Vabysmo, you have a new bispecific in-class molecule. This has generated a lot of excitement with strong data to support the sentiment. The one-year data released demonstrated stability up to 20 weeks, compared to the gold standard. That's pretty promising.”https://eyesoneyecare.com/resources/age-related-macular-degeneration-new-studies-optometry/
What is Vabysmo?
VEGF-A and Ang-2 are both culprits contributing to vision loss in AMD and DME by destabilizing blood vessels, leading to increased inflammation and leakage. By targeting a duo of disease pathways, Vabysmo halts the growth of these vessels, potentially reducing the risk for bleeding and fluid build-up.
Vabysmo accomplishes this through two mechanisms:
- Blocking vascular endothelial growth factor-A (VEGF-A), which is responsible for promoting the growth of new blood vessels (angiogenesis)
- Inhibiting angiopoietin-2 (Ang-2)
According to Michael Joseph Ammar, MD, a board-certified vitreoretinal surgeon with Retina Consultants San Diego, “In addition to blocking VEGF, Vabysmo also blocks the Ang-2 pathway resulting in improved vascular stability and less vessel leakage. This is a major advance in the treatment of these vision-threatening conditions, and based on the results we’ve seen thus far, will likely change how we manage them moving forward.”
What is Vabysmo used for?
Vabysmo is an intravitreal injection approved to treat both nAMD and DME.
How does Vabysmo work?
Vabysmo halts the growth of unstable blood vessels within the eye by targeting two disease pathways, thus blocking VEGF-A and inhibiting Ang-2.
What are the side effects of Vabysmo?
The main side effect of Vabysmo was shown to be conjunctival hemorrhage. However, due to its injectable status, the company offers warnings of endophthalmitis and retinal detachment potential risks. There could also be a temporary increase in intraocular pressure and is consistent with other intravitreal injections.
Though it was rare, only occurring in 7 out of 664 first-year clinical-trial patients with wet AMD and 25 out of 1,262 patients with DME, thromboembolic events, such as blood clots, heart attacks, and stroke were reported. In addition, Vabysmo is not recommended for those who are pregnant, plan to become pregnant, or are breastfeeding,
How often are Vabysmo injections required?
Vabysmo is administered every 4 weeks for the first loading doses and then normally at intervals from 8 weeks to 16 weeks apart.
What is the frequency of Vabysmo treatments?
Doctors and patients alike are most intrigued by the reduced frequency of treatment Vabysmo offers, with many patients experiencing equivalent visual acuity gains from fewer and less frequent treatments. After initial monthly loading doses, Vabysmo improved and maintained visual acuity when treatment is administered 1 to 4 months apart in the first year, based on evaluation of the patient’s anatomy and vision outcomes.
“The burden of frequent injections can impact people’s lives in many ways. Between the DME and nAMD populations, patients are often still working and must take time off for their visits,” Dr. Ammar said. “Some require family or friends for transportation or support. Even their health can be impacted as the burden of visits can interfere with other healthcare commitments. With Vabysmo, patients can have preserved vision with fewer visits.”
According to Roche, referring to the TENAYA and LUCERNE studies on nAMD, nearly 80% of faricimab-treated patients were able to go three months or longer between treatments during the first year. The YOSEMITE and RHINE studies in DME showed approximately 52% achieved 4-month dosing at one year. The studies combined yielded that, at the end of the first year, more than 70% of patients could go 3 months or longer between treatments.
Recommended dosage of Vabysmo
For nAMD, it is recommended to administer an intravitreal injection of 6 mg every 4 weeks for the first four doses. At 8 weeks and 12 weeks, OCT and visual acuity evaluations should be performed to see if the treatment interval should be modified. Based on anatomical and vision outcomes, patients may receive subsequent treatments every 2, 3, or 4 months. People with DME are initially given four monthly treatments. Subsequently, their treatment may be extended or reduced based on anatomical and vision outcomes, with a range of 1 to 4 months between doses. A second approved treatment regimen for DME involves 6 monthly loading doses, followed by treatment every two months.
Genentech noted no additional efficacy in the majority of patients when VABYSMO was dosed every 4 weeks compared to every 8 weeks. However, they acknowledged that some patients may need monthly dosing after the first four initial doses.
Who is the ideal candidate for Vabysmo?
As the first bispecific antibody approved for use in AMD and DME, Vabysmo shows promise for a large portion of that patient population. Patients should be open and eager to try Vabysmo as an alternative to current treatment. According to Dr. Almeida, “When it comes to intravitreal injections, we've been doing them for over a decade now, regularly, so patients are used to it. So this is going to be in line with the scope of care they are used to from their retina specialist, so I think that's going to be well taken.”
As for the ideal candidate, Dr. Almeida sees it yet to be determined whether that will be the patient who needs to extend or the individual who is already stable. However, he believes it will have a wide appeal to the whole population of DME and nAMD patients.
Dr. Ammar stated, “Patients who require frequent injections are especially well suited for a trial of Vabysmo, as it may allow them to increase the interval between their visits. These patients now have an option that may preserve their vision and provide longer durability. In contrast, patients who are responding well to existing treatments may be more hesitant to switch to a new medication.”
When will Vabysmo be available?
Upon its approval, Genentech announced that Vabysmo would be available in the United States “in the coming weeks” and that The European Medicines Agency was also evaluating it for use abroad.
Dr. Almeida has already been using Vabysmo samples with his patients and expects to have access to buy-and-bill as early as this month, March 2022. He stated, “I've already started adding it to my practice, and from the clinical trials and research side of it, I think it's gonna be an exciting drug.”
Dr. Ammar is also eager to incorporate Vabysmo into his AMD and DME treatment regimen: “I plan to adopt Vabysmo as a treatment for nAMD and DME as soon as it becomes available, now that the FDA has approved it. All clinical trials thus far have shown Vabysmo to be both safe and effective, and I am excited to offer it to my patients. As experience with Vabysmo grows, I expect it to become a larger and larger part of most practices.”
What is the cost of Vabysmo?
Genentech has reported the list price of Vabysmo to be $2,190 per treatment. This adds up to $13,140 for the first year for patients who receive treatment at four-month intervals and includes four initial monthly doses. The annual price is set to drop to $6,570 after the first year.
The future of Anti-VEGF therapy
Historically, anti-VEGF treatment improves vision in 1 out of 3 patients and stabilizes vision in 9 out of 10. The goal is to improve vision while making treatments more convenient and cost-efficient for patients. According to Dr. Ammar, “The future of anti-VEGF therapy is improved durability. We have treatments that work very well but don’t last very long. Vabysmo is a massive step forward, but we should strive to keep improving. Some exciting areas of research that may again change the landscape of anti-VEGF therapy are drug delivery systems and gene therapy.”
In the realm of alternative delivery systems, Genentech has also introduced Susvimo to treat adults with nAMD using an implant, which is inserted, filled, and then refilled as needed.
There are two schools of thought surrounding the future of treatment for nAMD. Dr. Almeida explained, “Right now, half the community is probably saying ‘Individually, injections are here to stay. It's what we do, and they're safe and fine.’ But, I'm probably of the second group who thinks we're not going to be doing individual injections every month, so we’re looking at longer therapies, like Vabysmo, and implantable therapies, like Susvimo.” Dr. Almeida also expressed his enthusiasm for gene therapies, which are already in clinical trials.
Closing thoughts on Vabysmo
As with any new treatment, Dr. Almeida understands that some ophthalmologists may be cautious about immediately implementing Vabysmo into their practice. Dr. Almeida suggests reviewing the data and choosing patients who closely align with those from the study. He also recommended, “Start slow and do an extra follow-up by bringing them in a bit sooner, so you get comfortable with the drug.”
