Getting Ophthalmic Biosimilars to Market Continues to Prove Difficult

On day 2 of AMCP 2023, in the session, “Biosimilars in Vision: Addressing Drug Trends and Managed Care Strategies,” representatives from Magellan Rx Management provided a detailed overview of current treatment options in the ophthalmic space and the impact that biosimilars could have in this space.

Sneha Sharma, PharmD, and Prerak Parikh, PharmD, both directors of specialty clinical solutions at Magellan Rx, also explored payer management strategies for anti–vascular endothelial growth factor (VEGF) therapeutics—the current standard of care in ophthalmic diseases—the challenges inherent with biosimilar interchangeability status, and the potential cost impact of ophthalmic drugs in the pipeline.

They shaped their discussions around 2 common retinal diseases: age-related macular degeneration (AMD), within which there is dry AMD (geographic atrophy) and wet AMD (wAMD; neovascular or exudative), and diabetic macular edema (DME).

“At present, wAMD accounts for 10% to 15% of AMD cases, but it’s responsible for 90% of severe vision loss, so as we speak to treatment options, we need to remember these are not cures,” she explained. “They are treatment options that are for chronic disease states and there are challenges associated with these treatments, as you’re injecting something into the eye.”

The prevalence of wAMD, Sharma added, is expected to reach the 22 million mark by 2050, with risk factors that include poor diet, smoking history, age older than 50, and hypertension. Current gold standard for first-line therapy for wAMD is VEGF inhibitors, as recommended by the American Academy of Ophthalmology (AAO) and the American Society of Retina Specialists. However, treatment-related challenges are ever present, including patient understanding and education on VEGF inhibitors and access andadherence to prescribed therapy.

Currently, 4.2 million individuals living with diabetes have diabetic retinopathy, of which DME is a potential complication. Experts, Sharma noted, expect 6.6% (1 of every 15) of patients to progress to retinopathy. The primary risk factor for DME is a build up of blood sugar. Here, the AAO also recommends VEGF inhibitors for first-line treatment—after bring diabetes under control—and this is commonly initiated in patients who have moderate/severe disease and visual acuity of 20/30 or worse. In addition, patients should be educated on glycemic control and the importance of yearly diabetic eye exams.

There are presently 8 VEGF inhibitors used in the ophthalmic space for AMD and DME:

• For both diseases, there are Avastin (bevacizumab), which is used off label; Beovu (brolucizumab-dbll); Lucentis (ranibizumab); Cimerli (ranibizumab-eqrn), biosimilar to Lucentis; Eylea (aflibercept); and Vabysmo (faricimab-avoa).
• For AMD only, there is Byooviz (ranibizumab-nuna), another biosimilar to Lucentis, and Susvimo (ranibizumab), which was recalled in October.

For AMD, these medications are administered from every 4 to every 16 weeks, with doses that range from 0.5 to 6.0 mg, and for DME, the dosing periods are every 4 to every 12 weeks, and doses range from 0.3 to 6.0 mg. The most cost-effective is Avastin, with a wholesale acquisition cost (WAC) and an average sales price (ASP) of $849 and $956, respectively, in AMD and DME. In comparison, for AMD, Lucentis has the highest WAC at $24,400 and Eylea has the highest ASP at $14,373, and for DME, Vabysmo has the highest WAC and ASP, at $17,520 and $18,082, respectively.

Looking at the market landscape through 2022 for Magellan, the highest total spend ($111,939,304) and cost/patient ($9092) were seen from Eylea; Avastin had the most patients (22,441) and the most claims (86,449); and Vabysmo had the highest cost/claim ($2971).

In contrast, Vabysmo had the least total spend ($20,795) and the fewest patients and claims (7 each), while Avastin had the lowest costs per patient ($467) and claim ($121).

Again looking at the market landscape, but instead using 2020 data on Medicare Part B spending, Eylea had a total spend of $3.5 billion-plus, with a cost/claim of $2439, and Lucentis had a total spend of $1.1 billion and a cost/claim of $1820. These numbers put these 2 drugs in the second and sixth slots for drug spend overall for 2020.

“I just want to mention here that a higher margin could be offered in the fee schedule for Avastin to help align with the brand name drugs—essentially and enhanced reimbursement,” Sharma noted.

If these treatment trends continue, for AMD, Lucentis will remain in the top slot for annual WAC and Eylea for annual ASP, and for DME, Eylea is tops in both. Looking at claims, according to Magellan data from 2019 to 2022, Avastin claims in the commercial, Medicare, and Medicaid spaces continued to rise steadily, while those for Eylea and Lucentis dropped.

With these numbers in flux, among the utilization management strategies in the ophthalmic space, biosimilars are picking up speed. There are 4 FDA-approved ophthalmic biosimilars, but only 2 are currently being used. Byooviz and Cimerli reference Lucentis and have potential for use as step therapy, but CMS recommends against using Mvasi and Zirabev, because there was not enough data to support their use—they are currently only approved for oncologic use.

Parikh picked up the discussion from here, providing insight and understanding into the ophthalmic biosimilar landscape, both the difficulties inherent in bring these therapeutics to market and the promises they hold in alleviating drug costs and increasing treatment access.

Compared with regular branded medications, which have a 10-step approval process that includes submission of an investigational new drug application, phase 1-3 clinical trials, facility review, and postmarketing surveillance, biosimilars and interchangeable biosimilars have abbreviated drug approval pathways, which makes it easier for them to enter the market, according to Parikh:

• Biosimilars: analytical studies > animal studies > clinical studies > comparative clinical studies
• Interchangeable biosimilars: analytical studies > animal studies > clinical studies > comparative clinical studies > switching study or additional clinical studies

However, there is a disconnect at the state and federal levels when it comes to getting these medications into the hands of patients. Although the FDA grants interchangeability status on a federal level, substitution and dispensing for pharmacies is determined at the state level, which is where pharmacy laws diverge regarding prescriber notification and permission, patient notification and consent, documentation requirements, and cost.

“All 50 states have some sort of laws regarding the interchangeability of biosimilars, and those laws vary from state to state,” Parikh explained. “So, to put things in perspective, about 40 states require the dispensing pharmacist document and notify the patient about any substitution.”

For example, for automatic substitution, New York allows the practice, North Carolina allows the move only if that drug will reduce patient spend, and Indiana does not allow automatic substitution. In addition, communication on the substitution is required in New York and Indiana but not in North Carolina, and the timelines to notify patients and providers of switching vary from not specified or not applicable to within 5 to 10 days.

“I want to note that even though the interchangeability designation allows for better access to biosimilars, the differences in state regulations still remain a hurdle,” Parikh underscored. “For the dispensing pharmacist at specialty pharmacies who are shipping to different states, they have to be aware of all these different laws.”

Additional difficulties for getting interchangeable biosimilars to market are evident in how they are managed as a pharmacy vs a medical benefit, with key differences evident for automatic substitution, claims adjudication, and preferencing strategy. For example, for automatic substitution, pharmacists have the capacity to switch when allowed by state law, but for medical drugs that may be purchased as buy and bill and are administered in a physician’s office, substitution decisions are often at the mercy of provider preference and product availability.

Further, for claims adjudication, this occurs at the National Drug Code level for the pharmacy benefit and at the Healthcare Common Procedure Coding System level for the medical benefit, and for preferencing strategy, interchangeability designation does not guarantee preferred formulary status, with pharmacy and medical benefit decisions often coming down to WAC and average wholesale price and ASP, respectively.

Within the ophthalmic biosimilar space specifically, there exist the hurdles of provider hesitancy, nonparity with indications, the cost of compounded bevacizumab, and costs of biosimilars vs their reference products. Payer solutions that Parikh proffered include the following:

• Automatic authorizations for interchangeable biosimilars that match reference product authorizations
• Allow for payment of interchangeable biosimilars at the claims level as long as there is an approved authorization for either product
• Provider education for those who express hesitancy

In addition, with compounded bevacizumab continuing to remain the most cost-effective drug in this category, Parikh recommended issuing preferred status to compounded bevacizumab over other anti-VEGF agents while continuing to monitor the ASP and utilization of biosimilars and their reference branded products.

At present, there are 9 ophthalmology biosimilars in the pipeline for macular degeneration and diabetic eye disease: 2 referencing Lucentis and 7, Eylea. All are currently in phase 3 studies, and a decision on MYL-1701P, which references Eylea, is expected sometime this year.

In addition, in the ophthalmology pipeline, there are 3 VEGF inhibitors in development (Eylea HD [aflibercept], Lytenava [bevacizumab-vikg], and KSI-301 [tarcocimab tedromer])—2 gene therapies (RGX-314 and ADVM-022 [ixoberogene soroparvovec]), and a complement inhibitor (Zimura [avacincaptad pegol]).

There are now more treatment options for AMD and DME, and these include biosimilars to Lucentis and a robust drug pipeline, Parikh noted as he concluded his presentation. In addition, it’s necessary for payers to be open to continually evolving their drug management strategies, now that biosimilars are creating market competition and driving down reference product costs, and interchangeability status allows for easier treatment substitution.

“That means plans need to be more watchful for any drops in ASP, changes in utilization and spend, and overall costs of the products,” he said, “to keep spend under control in this category and also lower patient costs.”