Many VEGF Inhibitor Options for Macular Degeneration and Edema, but Bevacizumab Is Still the Cost-Effectiveness Champ

Of the several classes of agents used to treat wet age-related macular degeneration or diabetic macular edema, no one drug does a better job of improving vision than the others. The only differentiating feature of the available biologics involves the frequency of intravitreal injections. There are large differences in prices, however, and this is why one drug category is utilized (off-label) far more often than the others combined.

At the 2023 annual meeting of the Academy of Managed Care Pharmacy in San Antonio last week, two sessions emphasized different perspectives on the preferred treatment pathway. The first was a satellite symposium sponsored by Genentech, where a retinal specialist stated that mainly because of the potential for better adherence with newer VEGF-inhibiting agents, he does not prescribe bevacizumab compounded for ophthalmologic use.

Yet, most health plans cover bevacizumab, and with good reason. It costs a fraction of that for the VEGF inhibitors ranibizumab and aflibercept, and the VEGF-/angiotensin-2 inhibitor faricimab.

The VEGF inhibitors are endorsed by the ophthalmologic societies as first-line treatment for both conditions, said Sneha Sharma, PharmD, Director of Specialty Clinical Solutions at Magellan Rx Management, in a separate education session. She stated that this includes off-label use of bevacizumab, also a VEGF inhibitor. The medical societies have been more circumspect regarding the use of compounded bevacizumab biosimilars. She emphasized that the previous compounding issues of lack of sterility or finding particles in the bevacizumab solution have been overcome.

One of the key unmet needs in the use of intravitreal injections of VEGF inhibitors is adherence. One retinal specialist admitted that the clinical trial outcomes with these agents are generally better than what is seen in real-world practice.

DrugCommentAge-Related Macular DegenerationDiabetic Macular EdemaNet Cost per Claim†
AvastinOff-Label Use, Bevacizumab$956$956$121
LucentisOriginator Ranibizumab$14,232$8,539$1,500
ByoovizBiosimilar Ranibizumab$13,868Not approvedN/R
CimerliBiosimilar Ranibizumab$16,320*$9,792*N/R
EyleaAfliberceptYear 1: $14,373; Subsequent Years: $10,780Year 1: $14,373; Subsequent Years: $10,780$2,064
BeovuBrolucizumabYear 1: $11,285; Subsequent Years: $7,524Year 1: $11,285; Subsequent Years: $7,524$2,020
VabysmoFaricimabYear 1: $13,561; Subsequent Years: $6,781Year 1: $13,561; Subsequent Years: $6,781$2,971
*Average sales price not yet available. Wholesale acquisition cost provided.
†Based on Magellan Rx data.
N/R = not reported (utilization data not yet available).
Adapted from Parikh P, Sharma S. Biosimilars in vision: Addressing drug trends and managed care strategies. Presented at 2023 annual meeting of the Academy of Managed Care Pharmacy, March 22, 2023.

All of these drugs will improve vision to a similar extent after the onset of disease, but ranibizumab and bevacizumab are meant to be injected monthly, with the possibility of extending the intervals between treatments after 3 months. Aflibercept is also given every month for the first three months, but it can be given every 8 weeks thereafter. Faricimab must be given monthly for at least four doses before extending out to perhaps every 12 weeks. Brolucizumab introduced initial dosing every 6 weeks for five doses. The key is that these products are all given monthly or every 6 weeks for three to five doses before extending the dosing interval. In practice though, patients may only receive three to five doses a year in total, skipping doses and resulting in concerns about preserving their vision.

The ranibizumab port system (Susvimo®) was an attempt to reduce the need for office visits to every 24 weeks, but (1) that product has been recalled and is not marketed and (2) this product is only indicated after patients have received at least two intravitreal injections with a VEGF inhibitor. There is one other important point to consider: One ranibizumab biosimilar (Byooviz®) and Susvimo are approved for wet age-related macular degeneration, not for diabetic macular edema.

Dr. Sharma said, “While 56% of patients in their database use [compounded] Avastin®, it only accounts for 8% of total spend in patients with AMD or DME.” In contrast, Eylea accounts for 34% of total patient use of a VEGF inhibitor but 78% of the total spend ($148 million for Magellan Rx). Eylea and Lucentis are both on Medicare’s list of highest annual drug expenditures ($3.5 billion and $1.1 billion, respectively).

Prerakumar Parikh, PharmD, also a Director, Specialty Clinical Solutions at Magellan Rx, stated that since Medicare had permitted step therapy to be used in 2019, Magellan Rx’s clients use of compounded Avastin as the initial step has steadily increased to 72% in 2022.

Although Cimerli® was granted an interchangeable designation, this is considered only relevant to products covered under the pharmacy benefit and distributed through pharmacies. Dr. Parikh explained this can still be utilized by payers, by “allowing use of the interchangeable biosimilar even if the prior authorization is for the reference product.”

Dr. Parikh stated that “Compounded bevacizumab continues to remain the most cost-effective drug within this category,” and he recommends “preferencing compounded bevacizumab over other anti-VEGF agents.”

Outlook Therapeutics’ manufactured ophthalmic formulation of bevacizumab has an FDA decision date of August 29, 2023. 

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