What circumstances would make brolucizumab your anti-VEGF drug of choice?
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Compelling evidence for brolucizumab
Exudative age-related macular degeneration is the leading cause of blindness in the developed world in people older than 65 years of age. Numerous intravitreal anti-VEGF medications (pegaptanib, bevacizumab, ranibizumab, aflibercept and brolucizumab) have been developed as therapeutic agents to suppress activity and improve visual outcomes. Although the therapies are effective, significant economic and caregiver burdens exist due to repeated intravitreal injections. As a result, many patients do not receive treatment in the real-world setting as has been demonstrated in standardized clinical trial settings, resulting in poorer visual outcomes.
Recently, Beovu (brolucizumab, Novartis), a single-chain antibody fragment inhibitor of all isoforms of VEGF-A, was approved for use in exudative AMD following two parallel phase 3 randomized clinical trials (HAWK and HARRIER), which demonstrated its safety, efficacy and an extended dosing regimen as compared with aflibercept. Brolucizumab has some potential advantages to current anti-VEGF medications. As demonstrated in the HAWK and HARRIER randomized clinical trials, brolucizumab demonstrated noninferiority with respect to best corrected visual acuity as compared with aflibercept at 48 weeks. However, in both studies, fewer brolucizumab eyes had disease activity (BCVA, subretinal/intraretinal fluid) than aflibercept eyes at week 16. Also, notably, both trials demonstrated that approximately half of the enrolled eyes receiving 6 mg brolucizumab were able to maintain an every 12-week dosing interval through week 48 after the initial three loading doses. Eyes receiving brolucizumab that did not require a rescue treatment between the final loading dose and the first every 12-week dose were likely to be maintained at every 12 weeks for the remainder of the study, thus demonstrating decreased disease activity and durability. Greater reductions in central subfield thickness were demonstrated in both trials by brolucizumab as compared with aflibercept at weeks 4, 8,12 and 16. Importantly, adverse ocular and systemic events were comparable between the two groups in both trials.
Based on the above data, and the fact that both HAWK and HARRIER involved treatment-naive patients with exudative AMD, there seems to be compelling evidence that brolucizumab may be a possible first-line treatment option based on safety, efficacy and durability. Further real-world data are warranted.
R. Ross Lakhanpal, MD, FACS, is a vitreoretinal surgeon with the Retina Care Center in Baltimore. Disclosure: Lakhanpal reports he is a consultant and speaker for Novartis.
Real-world adjustments needed
With the FDA approval of Beovu (brolucizumab, Novartis), the options for anti-VEGF treatments have expanded. In the treatment of neovascular macular degeneration, ophthalmologists can now choose among Lucentis (ranibizumab, Genentech), Eylea (aflibercept, Regeneron), Avastin (bevacizumab, Genentech) and brolucizumab. I have been asked to serve as the devil’s advocate for the incorporation of Beovu into our practices.
My first concern with brolucizumab resides with the real-world experience once it is used outside of the clinical trial arena. The clinical trials have created high expectations; however, we may find the duration of effect in individual patients not to be as long as anticipated. Our treatment and observation protocols may need to be adjusted to this new medication. Currently, with three well-known options at our disposal, this may be difficult to justify for many providers.
My second concern is our clinic’s pharmaceutical inventory management. Ordering and purchasing of pharmaceuticals for clinic use requires prediction of utilization for a given time period. As we divide the pool of patients into smaller subgroups of medication usage, purchasing the correct amount of medication units and keeping stock of our current inventory will become more difficult. In other words, it is easier to buy and use 20 syringes of bevacizumab than five each of bevacizumab, ranibizumab, aflibercept and brolucizumab.
Our options are to either increase the number of medications in our stock, thus tying up cash flow, become more sophisticated and exact with our pharmaceutical ordering, or risk not having enough units of a certain medicine during our clinic days.
Ultimately, I welcome the opportunity for competition between pharmaceutical companies in the anti-VEGF marketplace. Having more options is always better for our patients.
Jorge I. Calzada, MD, FACS, is the CEO and founder of Deep Blue Retina in Southaven, Mississippi. Disclosure: Calzada reports no relevant financial disclosures.